diff --git "a/data1/drugsInfo.csv" "b/data1/drugsInfo.csv" new file mode 100644--- /dev/null +++ "b/data1/drugsInfo.csv" @@ -0,0 +1,1486 @@ +DrugID,DrugName,DrugDescription,DrugTarget,DrugPharmacodynamics,DrugSmile,DrugMechanism,DrugConditions,DrugCategories +DB14509,Lithium carbonate,Lithium carbonateis a medication used to treat manic episodes of bipolar disorder.,"['O14732', 'P29218', 'P49841', 'P42263']","Lithium's mechanism of action is still unknownLabel. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors3,4.",[Li+].[Li+].[O-]C([O-])=O,"Lithium's mechanism of action is still unknownLabel. However, the “inositol depletion theory” suggests main potential targets. These targets are inositol monophosphatase, inositol polyphosphatase, and glycogen synthase kinase (GSK-),.The “Inositol depletion theory” suggests lithium behaves as an uncompetitive inhibitor of inositol monophosphatase in a manner inversely proportional to the degree of stimulus. This inhibition lowers levels of inositol triphosphate. However, stronger inhibitors of inositol monophosphatase are not as clinically effective and low levels of inositol triphosphate are associated with memory impairment,.Lithium acts on inositol polyphosphatase as an uncompetitive inhibitor. This inhibition is thought to have multiple downstream effects that have yet to be clarified.Lithium regulates phosphorylation of GSK- which regulates other enzymes through phosphorylation. Lithium can also inhibit GSK- through interfering with the magnesium ion in the active site.TargetActionsOrganismUInositol monophosphatase Not AvailableHumansUInositol monophosphatase Not AvailableHumansUGlycogen synthase kinase- betaNot AvailableHumansUGlutamate receptor Not AvailableHumans",[],"['Acids', 'Acids, Noncarboxylic', 'Alkalies', 'Anions', 'Antidepressive Agents', 'Antimanic Agents', 'Carbon Compounds, Inorganic', 'Carbonates', 'Carbonic Acid', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Electrolytes', 'Enzyme Inhibitors', 'Ions', 'Lithium Compounds', 'Mood Stabilizer', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'Nervous System', 'Neurotoxic agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Tranquilizing Agents']" +DB00996,Gabapentin,"Gabapentinis an anticonvulsant medication used in the management of peripheral neuropathic pains, postherpetic neuralgia, and partial-onset seizures.","['P54289', 'Q9NY47', 'A0A024R8I1', 'Q00975', 'P30542', 'O43525', 'Q9NR82']","Gabapentin is an anti-convulsant medication that inhibits the release of excitatory neurotransmitters, allowing for its use against pathologic neurotransmission such as that seen in neuropathic pain and seizure disorders.16,19It has a wide therapeutic index, with doses in excess of 8000 mg/kg failing to cause a fatal reaction in rats.21Gabapentin is ineffective in absence seizures and should be used in caution in patients with mixed seizure disorders involving absence seizures. Gabapentin has been associated with drug reaction with eosinophilia and systemic symptoms (DRESS), otherwise known as multi-organ hypersensitivity. This reaction can prove fatal and early symptoms such as fever, lymphadenopathy, and rash should be promptly investigated.16,17,19",NCC1(CC(O)=O)CCCCC1,"The precise mechanism through which gabapentin exerts its therapeutic effects is unclear.,The primary mode of action appears to be at the auxillary αδ- subunit of voltage-gated calcium channels (though a low affinity for the αδ- subunit has also been reported).,,The major function of these subunits is to facilitate the movement of pore-forming α subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons.There is evidence that chronic pain states can cause an increase in the expression of αδ subunits and that these changes correlate with hyperalgesia.Gabapentin appears to inhibit the action of αδ- subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters.It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin.There is some evidence that gabapentin also acts on adenosine receptors,and voltage-gated potassium channels,though the clinical relevance of its action at these sites is unclear.TargetActionsOrganismAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUVoltage-dependent N-type calcium channelinhibitorHumansUAdenosine receptor AagonistHumansUPotassium voltage-gated channel subfamily KQT member activatorHumansUPotassium voltage-gated channel subfamily KQT member activatorHumans",[],"['Acids, Acyclic', 'Acids, Carbocyclic', 'Amines', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Aminobutyrates', 'Analgesics', 'Anti-epileptic Agent', 'Anticonvulsants', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cyclohexanecarboxylic Acids', 'Cyclohexanes', 'Cycloparaffins', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Drugs causing inadvertant photosensitivity', 'Gabapentin and Prodrugs', 'Gabapentinoids', 'Miscellaneous Anticonvulsants', 'Nervous System', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Psychotropic Drugs', 'Sensory System Agents', 'Tranquilizing Agents']" +DB00740,Riluzole,Riluzoleis a glutamate antagonist used to treat amyotrophic lateral sclerosis.,"['Q14524', 'Q9UPY5']","Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in variousin vivoexperimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective.",NC1=NC2=C(S1)C=C(OC(F)(F)F)C=C2,"The mode of action of riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect: ) an inhibitory effect on glutamate release (activation of glutamate reuptake), ) inactivation of voltage-dependent sodium channels, and ) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansACystine/glutamate transporterinducerHumans",[],"['Anticonvulsants', 'BCRP/ABCG2 Substrates', 'Benzothiazoles', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Excitatory Amino Acid Agents', 'Excitatory Amino Acid Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Miscellaneous Central Nervous System Agents', 'Nervous System', 'Neuroprotective Agents', 'Neurotransmitter Agents', 'Protective Agents', 'Sulfur Compounds', 'Thiazoles']" +DB01083,Orlistat,Orlistatis a reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.,"['P16233', 'P07098', 'P49327']","Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.9,10",CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O,"Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.,TargetActionsOrganismAPancreatic triacylglycerol lipaseinhibitorHumansAGastric triacylglycerol lipaseinhibitorHumansUFatty acid synthaseinhibitorHumans",['Weight Reduction'],"['Alimentary Tract and Metabolism', 'Anti-Obesity Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Enzyme Inhibitors', 'Intestinal Lipase Inhibitor', 'Lactones', 'Lipase Inhibitors', 'Lipid Regulating Agents', 'Miscellaneous GI Drugs', 'Peripherally Acting Antiobesity Products']" +DB00759,Tetracycline,Tetracyclineis an antibiotic used to treat a wide variety of susceptible infections.,"['P02359', 'P0AG59', 'P0A7V3', 'P0A7W7', 'P0A7U3', 'P04156', 'C9EH48', 'Q9UM07']","Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.",[H][C@@]12C[C@@]3([H])C(=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C)C(=O)C1=C(O)C=CC=C1[C@@]3(C)O,"Tetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaUMajor prion proteininhibitorHumansUMultidrug translocase MdfANot AvailableEscherichia coliUProtein-arginine deiminase type-Not AvailableHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Naphthacenes', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Otologicals', 'Photosensitizing Agents', 'Protein Synthesis Inhibitors', 'Sensory Organs', 'Stomatological Preparations', 'Tetracyclines']" +DB00819,Acetazolamide,"Acetazolamideis a carbonic anhydrase inhibitor used to treat edema from heart failure or medications, certain types of epilepsy, and glaucoma.","['P00915', 'P00918', 'P22748', 'O43570', 'Q9ULX7', 'P07451', 'P43166', 'P29972']","Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion, in the treatment of certain convulsive disorders and in the promotion of diuresis in instances of abnormal fluid retention. Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.",CC(=O)NC1=NN=C(S1)S(N)(=O)=O,"The anticonvulsant activity of Acetazolamide may depend on a direct inhibition of carbonic anhydrase in the CNS, which decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension. The diuretic effect depends on the inhibition of carbonic anhydrase, causing a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen. This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, potassium, and water.TargetActionsOrganismACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansUAquaporin-inhibitorHumans",['Urine alkalinization therapy'],"['Anticonvulsants', 'Antiglaucoma Agents', 'Antiglaucoma Preparations and Miotics', 'Carbonic Anhydrase Inhibitors', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Natriuretic Agents', 'OAT1/SLC22A6 inhibitors', 'Ophthalmologicals', 'Photosensitizing Agents', 'Sensory Organs', 'Sulfonamides', 'Sulfur Compounds', 'Thiadiazoles', 'Thiazoles']" +DB00162,Vitamin A,Vitamin Ais a vitamin important for retinal function that is used clinically to correct vitamin A deficiency.,"['P05090', 'P41222', 'Q96NR8', 'Q92781', 'Q8NBN7', 'O94788', 'P00352', 'O95237', 'O75911', 'P47895', 'Q6NUM9', 'Q8TC12', 'Q9BTZ2', 'Q9HBH5', 'Q9NYR8']","Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-transretinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system.",C\C(=C/CO)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C,"Vision:Vitamin A (all-transretinol) is converted in the retina to the -cis-isomer of retinaldehyde or -cis-retinal. -cis-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. -cis-retinal, while attached to opsin in rhodopsin is isomerized to all-trans-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-trans-retinal is then released from opsin and reduced to all-trans-retinol. All-trans-retinol is isomerized to -cis-retinol in the dark, and then oxidized to -cis-retinal. -cis-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize -cisretinal rapidly. Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted.TargetActionsOrganismUApolipoprotein DligandHumansUProstaglandin-H D-isomeraseligandHumansURetinol dehydrogenase substrateHumansU-cis retinol dehydrogenasesubstrateHumansURetinol dehydrogenase substrateHumansURetinal dehydrogenase substrateHumansURetinal dehydrogenase substrateHumansULecithin retinol acyltransferasesubstrateHumansUShort-chain dehydrogenase/reductase substrateHumansUAldehyde dehydrogenase family member AsubstrateHumansUAll-trans-retinol ,-reductasesubstrateHumansURetinol dehydrogenase substrateHumansUDehydrogenase/reductase SDR family member substrateHumansURetinol dehydrogenase substrateHumansURetinol dehydrogenase substrateHumans",['Nutritional supplementation'],"['Adjuvants, Immunologic', 'Alimentary Tract and Metabolism', 'Alkenes', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anticarcinogenic Agents', 'Antioxidants', 'Biological Factors', 'Carotenoids', 'Compounds used in a research, industrial, or household setting', 'Cyclohexanes', 'Cyclohexenes', 'Cycloparaffins', 'Dermatologicals', 'Diagnostic Agents', 'Diet, Food, and Nutrition', 'Diterpenes', 'Esters', 'Food', 'Growth Substances', 'Immunologic Factors', 'Micronutrients', 'Nasal Preparations', 'Ophthalmologicals', 'Physiological Phenomena', 'Pigments, Biological', 'Polyenes', 'Protective Agents', 'Retinoids', 'Retinoids for Topical Use in Acne', 'Sensory Organs', 'Terpenes', 'Tests for Fat Absorption', 'Vitamin A', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00795,Sulfasalazine,"Sulfasalazineis a salicylate used to treat Crohn's disease, ulcerative colitis, and rheumatoid arthritis.","['P09917', 'P35354', 'P23219', 'P24752', 'P04054', 'Q9UPY5', 'P19838', 'Q00653', 'O14920', 'O15111', 'P37231']","The mode of action of sulfasalazine or its metabolites, 5-aminosalicylic acid and sulfapyridine, is still under investigation but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal andin vitromodels, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver, and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of sulfasalazine, sulfapyridine, and 5-aminosalicylic acid have indicated that the major therapeutic action may reside in the 5-aminosalicylic acid moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown.16",OC(=O)C1=CC(=CC=C1O)\N=N\C1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=C1,"Although the exact mechanism of action of sulfasalazine is not fully understood, it is thought to be mediated through the inhibition of various inflammatory molecules.Research have found that sulfasalazine and its metabolites, mesalazine and sulfapyridine, can inhibit leukotrienes and prostaglandins by blocking the cyclo-oxygenase and lipoxygenase pathway.Specific enzymes that were investigated include phospholipase A, cyclooxygenase- (COX-), cyclooxygenase- (COX), and arachidonate -lipoxygenase.,,,Inhibitory activities on other non-arachidonic acid derivatives have also been observed, including PPAR gamma, NF-Kb, and IkappaB kinases alpha and beta.,,,TargetActionsOrganismAArachidonate -lipoxygenaseinhibitorHumansAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansAAcetyl-CoA acetyltransferase, mitochondrialinhibitorHumansAPhospholipase AantagonistHumansUCystine/glutamate transporterinhibitorHumansUNuclear factor NF-kappa-B p subunitinhibitorHumansUNuclear factor NF-kappa-B p subunitinhibitorHumansAInhibitor of nuclear factor kappa-B kinase subunit betainhibitorHumansUInhibitor of nuclear factor kappa-B kinase subunit alphaNot AvailableHumansUPeroxisome proliferator-activated receptor gammaagonistHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Amides', 'Aminosalicylate', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antirheumatic Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Gastrointestinal Agents', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'Methemoglobinemia Associated Agents', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'NTCP Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Salicylates', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB00982,Isotretinoin,Isotretinoinis a retinoid used to treat severe recalcitrant acne.,"['P13631', 'P10276']",The pharmacodynamics of isotretinoin are poorly understood.Label,C\C(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C\C(O)=O,"Isotretinoin produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis.These actions reduce sebum production, preventing the blockage of pores, and growth of acne causing bacteria.Isotretinoin and -oxo-isotretinoin both significantly reduce the production of sebum.,LabelIsotretinoin has little to no affinity for retinol binding proteins (RBPs) and retinoic acid nuclear receptors (RARs).Tretinoin and -oxo-tretinion bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by isotretinoin.Isotretinoin induces apoptosis in sebocytes, leading to a decrease in sebum production.Isotretinoin also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism.Isotretinoin does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne causing bacteria.It may also increase immune mechanisms and alter chemotaxis of monocytes to reduce inflammation.There is preliminary evidence suggesting isotretinoin may interact with FoxO, which may explain a substantial number of isotretinoin's unexplained actions.TargetActionsOrganismURetinoic acid receptor gammaNot AvailableHumansURetinoic acid receptor alphaother/unknownHumans",[],"['Agents Causing Muscle Toxicity', 'Alkenes', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Systemic Use', 'Anti-Acne Preparations for Topical Use', 'Biological Factors', 'Carotenoids', 'Cyclohexanes', 'Cyclohexenes', 'Cycloparaffins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Hydrocarbons, Acyclic', 'Misc. Skin and Mucous Membrane Agents', 'Noxae', 'Photosensitizing Agents', 'Pigments, Biological', 'Polyenes', 'Retinoids', 'Retinoids for Topical Use in Acne', 'Retinoids for Treatment of Acne', 'Teratogens', 'Terpenes', 'Toxic Actions']" +DB01017,Minocycline,Minocyclineis a tetracycline analog used to treat a wide variety of infections in the body.,"['P0A7X3', 'P0A7V8', 'P01584', 'P09917', 'P14780', 'P15692', 'P29466', 'P42574', 'P99999', 'P28482', 'P53779', 'Q15759', 'P53778', 'O15264', 'Q16539', 'Q8TD08', 'P27361', 'P31152', 'Q16659', 'Q13164', 'P45983', 'P45984', 'P35228']","Minocycline is a tetracycline antibiotic that binds to the bacterial 30S ribosomal subunit and interferes with protein synthesis. It is generally given 2-4 times daily, so the duration of action is short.12Intravenous minocycline should not exceed 400mg in 24 hours.14Patients should be counselled regarding the risks related to tooth and bone development, pseudomembranous colitis, central nervous system side effects, and pseudotumor cerebri.10",[H][C@@]12CC3=C(C(O)=CC=C3N(C)C)C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2,"Tetracyclines enter bacterial cells through OmpF and OmpC porins by coordinating with cations like magnesium.This allows tetracyclines into the periplasm where they dissociate, allowing the lipophilic tetracycline to diffuse into the bacterial cytoplasm.Tetracyclines prevent aminoacyl-tRNA from binding to the S ribosome, inhibiting protein synthesis.,,,TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)US ribosomal RNAinhibitorEnteric bacteria and other eubacteriaUInterleukin- betamodulatorHumansUArachidonate -lipoxygenaseinhibitorHumansUMatrix metalloproteinase-inhibitorHumansUVascular endothelial growth factor AinhibitorHumansUCaspase-negative modulatorHumansUCaspase-negative modulatorHumansUCytochrome cnegative modulatorHumansUMitogen-activated Protein KinasesinhibitorHumansUNitric oxide synthase, inducibleinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Antiinfectives for Systemic Use', 'Antiinfectives for Treatment of Acne', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Naphthacenes', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Photosensitizing Agents', 'Stomatological Preparations', 'Tetracyclines']" +DB01406,Danazol,Danazolis a synthetic steroid and pituitary gonadotropin inhibitor used in the treatment of endometriosis and symptomatic treatment of severe pain and tenderness associated with benign fibrocystic breasts.,"['P03372', 'P10275', 'P06401', 'P30968', 'Q96P88', 'P13500']","Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis, but its role as a treatment for endometriosis has been largely replaced by the gonadotropin-releasing hormone (GnRH) agonists. Danazol has antigonadotropic and anti-estrogenic activities. Danazol acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties.",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC3=C(C[C@]12C)C=NO3,"As a gonadotropin inhibitor, danazol suppresses the pituitary-ovarian axis possibly by inhibiting the output of pituitary gonadotropins. Danazol also depresses the preovulatory surge in output of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby reducing ovarian estrogen production. Danazol may also directly inhibits ovarian steroidogenesis; bind to androgen, progesterone, and glucocorticoid receptors; bind to sex-hormone-binding globulin and corticosteroid-binding globulin; and increases the metabolic clearance rate of progesterone. Another mechanism of action by which danazol may use to facilitate regression of endometriosis is by decreasing IgG, IgM, and IgA concentrations, as well as phospholipid and IgG isotope autoantibodies. In the treatment of endometriosis, as a consequence of suppression of ovarian function, danazol causes both normal and ectopic endometrial tissues to become inactive and atrophic. This leads to anovulation and associated amenorrhea. In fibrocystic breast disease, the exact mechanism of action of danazol is unknown, but may be related to suppressed estrogenic stimulation as a result of decreased ovarian production of estrogen. A direct effect on steroid receptor sites in breast tissue is also possible. This leads to a disappearance of nodularity, relief of pain and tenderness, and possibly changes in the menstrual pattern. In terms of hereditary angioedema, danazol corrects the underlying biochemical deficiency by increasing serum concentrations of the deficient C esterase inhibitor, resulting in increased serum concentrations of the C component of the complement system. (Source: PharmGKB)TargetActionsOrganismAEstrogen receptor alphaagonistHumansAAndrogen receptoragonistHumansAProgesterone receptoragonistHumansAGonadotropin-releasing hormone receptornegative modulatorHumansAPutative gonadotropin-releasing hormone II receptornegative modulatorHumansUC-C motif chemokine inhibitorHumans",[],"['Androgens', 'Antigonadotropins and Similar Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Estrogen Antagonists', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Pregnadienes', 'Pregnanes', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Thyroxine-binding globulin inhibitors']" +DB00997,Doxorubicin,"Doxorubicinis a medication used to treat various cancers, including AIDS-associated Kaposi's Sarcoma and metastatic cancers.","['P11388', 'Q14978', 'P11387', 'Q02880']","Doxorubicin is a cytotoxic, cell-cycle non-specific anthracycline antibiotic.2,37It is generally thought to exert its antitumor effect by destabilizing DNA structures through intercalation, thus introducing DNA strand breakages and damages.34,35,37Not only does it alter the transcriptomes of the cells, failure in repairing DNA structures can also initiate the apoptotic pathways.37,38Additionally, doxorubicin intercalation can also interfere with vital enzyme activity, such as topoisomerase II, DNA polymerase, and RNA polymerase, leading to cell cycle arrests.37Finally, doxorubicin can also generate cytotoxic reactive oxygen species to exert cellular damages.29",COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O,"Generally, doxorubicin is thought to exert its antineoplastic activity through primary mechanisms: intercalation into DNA and disrupt topoisomerase-mediated repairs and free radicals-mediated cellular damages.Doxorubicin can intercalate into DNA through the anthraquinone ring, which stabilizes the complex by forming hydrogen bonds with DNA bases.Intercalation of doxorubicin can introduce torsional stress into the polynucleotide structure, thus destabilizing nucleosome structures and leading to nucleosome eviction and replacement.,Additionally, the doxorubicin-DNA complex can interfere with topoisomerase II enzyme activity by preventing relegation of topoisomerase-mediated DNA breaks, thus inhibiting replication and transcription and inducing apoptosis.,Moreover, doxorubicin can be metabolized by microsomal NADPH-cytochrome P- reductase into a semiquinone radical, which can be reoxidized in the presence of oxygen to form oxygen radicals.,Reactive oxygen species have been known to cause cellular damage through various mechanisms, including lipid peroxidation and membrane damage, DNA damage, oxidative stress, and apoptosis.Although free radicals generated from this pathway can be deactivated by catalase and superoxide dismutase, tumor and myocardial cells tend to lack these enzymes, thus explaining doxorubicin's effectiveness against cancer cells and tendency to cause cardiotoxicity.,,TargetActionsOrganismADNA topoisomerase -alphainhibitorHumansADNAintercalationHumansUNucleolar and coiled-body phosphoprotein Not AvailableHumansADNA topoisomerase inhibitorHumansADNA topoisomerase -betainhibitorHumans",[],"['Anthracycline Topoisomerase Inhibitor', 'Anthracyclines', 'Anthracyclines and Related Substances', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Carbohydrates', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Cytotoxic Antibiotics and Related Substances', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00993,Azathioprine,"Azathioprineis an immunosuppressant used to prevent renal transplant rejection, treat rheumatoid arthritis, Crohn's disease, and ulcerative colitis.",['P63000'],"Azathioprine is an immunosuppressive agent which functions through modulation of rac1 to induce T cell apoptosis, as well as other unknown immunosuppressive functions.5It has a long duration of action as it is given daily, and has a narrow therapeutic index.12Patients should be counselled regarding the risk of malignancies of the skin and lymphomas.12",CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O,"Azathioprine's mechanism of action is not entirely understood but it may be related to inhibition of purine synthesis, along with inhibition of B and T cells.-thioguanine triphosphate, a metabolite of azathioprine, modulates activation of rac when costimulated with CD, inducing T cell apoptosis.This may be mediated through rac's action on mitogen-activated protein kinase, NF-kappaB.TargetActionsOrganismURas-related C botulinum toxin substrate modulatorHumans",[],"['Antimetabolites', 'Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'Carbohydrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Immunosuppressive Agents', 'Immunotherapy', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'P-glycoprotein substrates', 'Purine Antimetabolite', 'Purines', 'Sulfhydryl Compounds', 'Sulfur Compounds', 'Thionucleosides', 'Thiopurine Analogs', 'Toxic Actions']" +DB00480,Lenalidomide,Lenalidomideis a thalidomide derivative used to treat multiple myeloma and anemia in low to intermediate risk myelodysplastic syndrome.,"['Q96SW2', 'O14788', 'P33151', 'P35354']","In hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity.3Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties.5Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells.7It delays tumour growth in nonclinical hematopoietic tumour modelsin vivo, including multiple myeloma.9Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis.7Lenalidomide also mediates indirect antitumour effects via its immunomodulatory actions: it inhibits the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies. Lenalidomide enhances the host immunity by stimulating T cell proliferation and enhancing the activity of natural killer (NK) cells.1,6,7Lenalidomide is about 100–1000 times more potent in stimulating T cell proliferation thanthalidomide.3In vitro, it enhances antibody-dependent cell-mediated cytotoxicity (ADCC), which is even more pronounced when used in combination with rituximab.9Due to its anti-inflammatory properties, lenalidomide has been investigated in the context of inflammatory and autoimmune diseases, such as amyotrophic lateral sclerosis.8",NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O,"Lenalidomide is a drug with multiple mechanisms of action. Lenalidomide exerts immunomodulating effects by altering cytokine production, regulating T cell co-stimulation, and enhancing the NK cell-mediated cytotoxicity.Lenalidomide directly inhibits the cullin ring E ubiquitin ligase complex: upon binding to cereblon, a substrate adaptor of the complex, lenalidomide modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros (IKZF), Aiolos (IKZF), and CKα.These substrates are then tagged for ubiquitination and subsequent proteasomal degradation. IKZF and IKZF are B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells. IKZF also regulates the expression of interferon regulatory factor (IRF), which is a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of lenalidomide can be partly explained by the degradation of IKZF, since it is a repressor of the interleukin gene (IL): as lenalidomide decreases the level of IKZF, the production of IL- increases, thereby increasing the proliferation of natural killer (NK), NKT cells, and CD+ T cells.Lenalidomide inhibits the production of pro-inflammatory cytokines TNF-α, IL-, IL-, and IL-, while elevating the production of anti-inflammatory cytokine IL-.Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD T-cell proliferation and increases the production of IL- and IFN-γ in T lymphocytes, which enhances NK cell cytotoxicity and ADCC. It inhibits the expression and function of T-regulatory cells, which are often overabundant in some hematological malignancies.Lenalidomide directly exerts antitumour effects by inhibiting the proliferation and inducing apoptosis of tumour cells. Lenalidomide triggers the activation of pro-apoptotic caspase-, enhances tumour cell sensitivity to FAS-induced apoptosis, and downregulates NF-κB, an anti-apoptotic protein.Independent of its immunomodulatory effects, lenalidomide mediates anti-angiogenic effects by inhibiting angiogenic growth factors released by tumour cells, such as vascular endothelial growth factor (VEGF), basic fibroblastic-growth factor (BFGF), and hepatocyte-growth factor.In vitro, lenalidomide inhibits cell adhesion molecules such as ICAM-, LFA-, β and β integrins, as well as gap-junction function, thereby preventing metastasis of malignant cells.TargetActionsOrganismAProtein cerebloninhibitorHumansATumor necrosis factor ligand superfamily member inhibitorHumansUCadherin-antagonistHumansUProstaglandin G/H synthase negative modulatorHumans",[],"['Acids, Carbocyclic', 'Angiogenesis Inhibitors', 'Angiogenesis Modulating Agents', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Drugs that are Mainly Renally Excreted', 'Growth Inhibitors', 'Growth Substances', 'Heterocyclic Compounds, Fused-Ring', 'Imides', 'Immunologic Factors', 'Immunosuppressive Agents', 'Isoindoles', 'Myelosuppressive Agents', 'P-glycoprotein substrates', 'Phthalic Acids', 'Phthalimides', 'Piperidines', 'Piperidones', 'Thalidomide Analog']" +DB00871,Terbutaline,Terbutalineis a beta-2 adrenergic agonist used as a bronchodilator and to prevent premature labor.,"['P07550', 'P13945', 'P08588']","Terbutaline is a beta-2 adrenergic receptor agonist indicated to treat reversibly bronchospasm in asthmatic patients with bronchitis and emphysema.16,17It has a short duration as the inhaled form is taken up to three times daily, and the therapeutic window is wide.16,17",CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1,"Terbutaline is a selective beta- adrenergic receptor agonist.Agonism of these receptors in bronchioles activates adenylyl cyclase, increasing intracellular cyclic adenosine monophosphate (cAMP).Increased cAMP decreases intracellular calcium, activating protein kinase A, inactivating myosin light-chain kinase, activating myosin light-chain phosphatase, and finally relaxing smooth muscle in the bronchiole.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUBeta- adrenergic receptorantagonistHumans",['Airway secretion clearance therapy'],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cholinesterase Inhibitors', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Ethanolamines', 'Neurotransmitter Agents', 'OCT2 Substrates', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Reproductive Control Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetics', 'Tocolytic Agents']" +DB14001,alpha-Tocopherol succinate,alpha-Tocopherol succinateis a form of vitamin E used to treat and prevent vitamin deficiencies.,"['Q9UDX4', 'O76054', 'O75469', 'P05771', 'P09917', 'P17252', 'P23743', 'Q9Y6T7', 'Q16760', 'P52429', 'Q86XP1', 'P49619', 'O75912', 'Q5KSL6', 'P52824', 'Q13574']","Of the eight separate variants of vitamin E, alpha-tocopherol is the predominant form of vitamin E in human and animal tissues, and it has the highest bioavailability16. This is because the liver preferentially resecretes only alpha-tocopherol by way of the hepatic alpha-tocopherol transfer protein (alpha-TTP); the liver metabolizes and excretes all the other vitamin E variants, which is why blood and cellular concentrations of other forms of vitamin E other than alpha-tocopherol are ultimately lower15.Furthermore, the term alpha-tocopherol generally refers to a group of eight possible stereoisomers which is often called all-rac-tocopherol for being a racemic mixture of all eight stereoisomers12,16. Of the eight stereoisomers, the RRR-alpha-tocopherol - or sometimes referred to as the d-alpha-tocopherol - stereoisomer is the naturally occurring form of alpha-tocopherol that is perhaps best recognized by the alpha-TTP12,16and has been reported to demonstrate approximately twice the systemic availability of all-rac-tocopherol16.As a result, often times (but certainly not always) the discussion of vitamin E - at least within the context of using the vitamin for health-related indications - is generally in reference to the use of RRR- or d-alpha-tocopherol.Subsequently, without further evidence to suggest otherwise, alpha-tocpherol succinate is generally believed to undergo a logical de-esterification in the gastrointestinal tract before being subsequently absorbed as free tocopherol6,7.",[H][C@@](C)(CCCC(C)C)CCC[C@@]([H])(C)CCC[C@]1(C)CCC2=C(C)C(OC(=O)CCC(O)=O)=C(C)C(C)=C2O1,"Without further evidence to suggest otherwise, alpha-tocpherol succinate is generally believed to undergo a logical de-esterification in the gastrointestinal tract before being subsequently absorbed as free tocopherol,. The free alpha-tocopherol is therefore available and capable of the following activities.Vitamin E's antioxidant capabilities are perhaps the primary biological action associated with alpha-tocopherol. In general, antioxidants protect cells from the damaging effects of free radicals, which are molecules that consist of an unshared electron. These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS). In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases. Moreover, the human body naturally forms ROS when it converts food into energy and is also exposed to environmental free radicals contained in cigarette smoke, air pollution, or ultraviolet radiation from the sun. It is believed that perhaps vitamin E antioxidants might be able to protect body cells from the damaging effects of such frequent free radical and ROS exposure.Specifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions. The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins. Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids. Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical. This tocopheroxyl radical can then undergo various possible reactions: it could (a) be reduced by other antioxidants to tocopherol, (b) react with another tocopheroxyl radical to form non-reactive products like tocopherol dimers, (c) undergo further oxidation to tocopheryl quinone, or (d) even act as a prooxidant and oxidize other lipids.In addition to the antioxidant actions of vitamin E, there have been a number of studies that report various other specific molecular functions associated with vitamin E. For example, alpha-tocopherol is capable of inhibiting protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes. In particular, protein kinase C inhibition by alpha-tocopherol is partially attributable to its attenuating effect on the generation of membrane-derived dialglycerol, a lipid that facilitates protein kinase C translocation, thereby increasing its activity.In addition, vitamin E enrichment of endothelial cells downregulates the expression of intercellular cell adhesion molecule (ICAM-) and vascular cell adhesion molecule- (VCAM-), thereby decreasing the adhesion of blood cell components to the endothelium.Vitamin E also upregulates the expression of cytosolic phospholipase A and cyclooxygenase-. The increased expression of these two rate-limiting enzymes in the arachidonic acid cascade explains the observation that vitamin E, in a dose-dependent fashion, enhanced the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans.Furthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions. The vitamin can also evidently inhibit the plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation of platelets. Moreover, vitamin E may also be able to decrease monocyte adhesion to the endothellium by downregulating expression of adhesion molecules and decreasing monocyte superoxide production.Given these proposed biological activities of vitamin E, the substance continues to generate ongoing interest and studies in whether or not vitamin E can assist in delaying or preventing various diseases with any one or more of its biologic actions. For instance, studies continue to see whether vitamin E's ability to inhibit low-density lipoprotein oxidation can aid in preventing the development of cardiovascular disease or atherogenesis.Similarly, it is also believed that if vitamin E can decrease the chance of cardiovascular disease then it can also decrease the chance of related diabetic disease and complications. In much the same way, it is also believed that perhaps the antioxidant abilities of vitamin E can neutralize free radicals that are constantly reacting and damaging cellular DNA. Furthermore, it is also believed that free radical damage does contribute to protein damage in the ocular lens - another free radical-mediated condition that may potentially be prevented by vitamin E use. Where it is also suggested that various central nervous system disorders like Parkinson's disease, Alzheimer's disease, Down's syndrome, and Tardive Dyskinesia possess some form of oxidative stress component, it is also proposed that perhaps vitamin E use could assist with its antioxidant action.There have also been studies that report the possibility of vitamin E supplementation can improve or reverse the natural decline in cellular immune function in healthy, elderly individuals.As of this time, however, there is either only insufficient data or even contradicting data (where certain doses of vitamin E supplementation could even potentially increase all-cause mortality)on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.Furthermore, there are ongoing studies that demonstrate alpha-tocopherol succinate's unique possession of capabilities that allow it to induce differentiation, inhibit proliferation and apoptosis in cancer cells, enhance the growth-inhibitory effect of ionizing radiation, hyperthermia, and some chemotherapeutic agents and biological response modifiers on tumor cells, all the while protecting normal cells against any adverse effects. Despite being able to demonstrate such effects on animal and human cells in culture, the value of these effects has not drawn significant attention from researchers and clinicians and nor has the specific mechanisms of action been elucidated. Additionally, other studies have also shown that alpha-tocopherol succinate seemingly possesses an ability exclusive from other tocopherol esters to inhibit and minimize prostaglandin E production in human lung epithelial cells. Considering increased prostaglandin E production has been observed frequently in lung cancer patients, there may be another avenue in which alpha-tocopherol succinate may be able to treat lung cancer. Nevertheless, the possibility of such activity requires further elucidation.TargetActionsOrganismUSEC-like protein Not AvailableHumansUSEC-like protein Not AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumansUProtein kinase C beta typeNot AvailableHumansUArachidonate -lipoxygenaseNot AvailableHumansUProtein kinase C alpha typeNot AvailableHumansUDiacylglycerol kinaseNot AvailableHumansULung epithelial cellsNot AvailableHumans",['Nutritional supplementation'],"['Antioxidants', 'Benzopyrans', 'Biological Factors', 'Compounds used in a research, industrial, or household setting', 'Diet, Food, and Nutrition', 'Food', 'Heterocyclic Compounds, Fused-Ring', 'Micronutrients', 'Physiological Phenomena', 'Protective Agents', 'Pyrans', 'Tocopherols', 'Vitamin E', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00370,Mirtazapine,Mirtazapineis a tetracyclic antidepressant used in the treatment of major depression and is used off-label as a drug for insomnia and to increase appetite.,"['P28223', 'Q9UE69', 'P08913', 'P35348', 'P35368', 'P25100', 'P28335', 'P41145', 'P35367']","General effects and a note on suicidalityMirtazapine is effective in treating moderate to severe depression and treats many symptoms normally associated with this condition. These symptoms may include disturbed sleep, lack of appetite, and anhedonia, in addition to anxiety.2,22,29. It is important to note that suicidal ideation and behavior may emerge or increase during treatment with mirtazapine, as with any other antidepressant. This risk is especially pronounced in younger individuals. Patients, medical professionals, and families should monitor for suicidal thoughts, worsening depression, anxiety, agitation, sleep changes, irritable behavior, aggression, impulsivity, restlessness, and other unusual behavior when this drug is taken or the dose is adjusted.LabelDo not administer mirtazapine to children. When deciding to prescribe this drug, carefully consider the increased risk of suicidal thoughts and behavior, especially in young adults.LabelEffects on appetite and weight gainIn addition to the above effects, mirtazapine exerts stimulating effects on appetite, and has been used for increasing appetite and decreasing nausea in cancer patients.14,15Some studies and case reports have shown that this drug improves eating habits and weight gain in patients suffering from anorexia nervosa when administered in conjunction with psychotherapy and/or other psychotropic drugs.16,23In a clinical trial, women with depression experienced a clinically significant mean increase in body weight, fat mass, and concentrations of leptin when treated with mirtazapine for a 6-week period, with a lack of effect on glucose homeostasis.18Effects on sleepThe use of mirtazapine to treat disordered sleep has been leveraged from its tendency to cause somnolence, which is a frequently experienced adverse effect by patients taking this drug.8,20,LabelMirtazapine has been shown to exert beneficial effects on sleep latency, duration, and quality due to its sedating properties.17Insomnia is a common occurrence in patients with depression, and mirtazapine has been found to be efficacious in treating this condition.8",CN1CCN2C(C1)C1=CC=CC=C1CC1=C2N=CC=C1,"SummaryThe mechanism of action of mirtazapine is not fully understoodLabelbut may be explained by its effects on central adrenergic and serotonergic activity. This drug exhibits a fast onset of action, a high level of response, a manageable side-effect profile, and dual noradrenergic and serotonergic effects that are unique from the effects of other antidepressants.Effects on various receptorsIt has been shown that both noradrenergic and serotonergic activity increase following mirtazapine administration. The results of these studies demonstrate mirtazapine exerts antagonist activity at presynaptic α-adrenergic inhibitory autoreceptors and heteroreceptors in the central nervous system. This is thought to lead to enhanced noradrenergic and serotonergic activityLabel, which are known to improve the symptoms of depression and form the basis of antidepressant therapy.,Mirtazapine is a strong antagonist of serotonin -HT and -HT receptors. It has not been found to bind significantly to the serotonin -HTA and -HTB receptorsLabelbut indirectly increases -HTA transmission.In addition to the above effects, mirtazapine is a peripheral α-adrenergic antagonist. This action may explain episodes of orthostatic hypotension that have been reported after mirtazapine use.LabelMirtazapine is a potent histamine (H) receptor antagonist, which may contribute to its powerful sedating effects.LabelThe pain-relieving effects of mirtazapine may be explained by its effects on opioid receptors.,TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansAHT serotonin receptorantagonistHumansAAlpha-A adrenergic receptorantagonistHumansUAlpha- adrenergic receptorsantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUKappa-type opioid receptoragonistHumansNHistamine H receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-2 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Anti-Anxiety Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Antidepressive Agents, Tetracyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Miscellaneous Antidepressants', 'Nervous System', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB00476,Duloxetine,"Duloxetineis a serotonin norepinephrine reuptake inhibitor used to treat generalized anxiety disorder, neuropathic pain, osteoarthritis, and stress incontinence.","['P31645', 'P23975', 'Q01959']","Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter.9,10This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores.11It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg.Action at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain.10,12This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys.13While duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained.14Increased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling.Label,16",CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1,"Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake.Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors.Action on the external urinary sphincter is mediated via duloxetine's CNS effects. Increased serotonin and norepinephrine concentrations in Onuf's nucleus leads to increased activation of -HT, -HT, and αadrenergic receptors.,-HTand αare both Gqcoupled and their activation increases the activity of the inositol trisphosphate/phospholipase C (IP/PLC) pathway.This pathway leads to release of intracellular calcium stores, increasing intracellular calcium concentrations, and facilitating neuronal excitability. -HTfunctions as a ligand-gated sodium channel which allows sodium to flow into the neuron when activated. Increased flow of sodium into the neuron contributes to depolarization and activation of voltage gated channels involved in action potential generation. The combined action of these three receptors contributes to increased excitability of the pudendal motor nerve in response to glutamate.Also related to duloxetine's action at the spinal cord is its modulation of pain. Increasing the concentration of serotonin and norepinephrine in the dorsal horn of the spinal cord increases descending inhibition of pain through activation of -HTA, -HTB, -HTD, -HT, -HT, α-adrenergic, and α-adrenergic receptors.-HT, -HT, and α-adrenergic mediate neuronal activation as described above. The activated neuron in this case is the GABAergic inhibitory interneuron which synapses onto the nociceptive projection neuron to inhibit the transmission of painful stimuli to the brain. The -HTand αreceptors are Gi/Gocoupled and their activation leads to increased potassium current through inward rectifier channels and decreased adenylyl cyclase/protein kinase A signaling which contributes to neuronal inhibition.,These inhibitory receptors are present on the projection neuron itself as well as the dorsal root ganglion which precedes it and serves to directly suppress the transmission of painful stimuli.The mechanisms involved in duloxetine's benefits in depression and anxiety have not been fully elucidated. Dysfunctional serotonin and norepinephrine signaling are thought to be involved and increases in the availability of these neurotransmitters at the synaptic cleft thought to mediate a therapeutic effect.It is postulated that the involvement of serotonin and norepinephrine in area responsible for emotional modulation such as the limbic system contributes to the effects in mood disorders specifically but this has yet to be confirmed.Duloxetine's hypertensive effect is related to its intended pharmacological effect. Increased availability of norepinephrine leads to activation of adrenergic receptors on the vascular endothelium. Since the action of αreceptors predominates, vasoconstriction results as the Gqcoupled receptor mediates calcium release from the sarcoplasmic reticulum to facilitate smooth muscle contraction.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Analgesics', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Uptake Inhibitors', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin and Noradrenaline Reuptake Inhibitors', 'Serotonin Modulators', 'Sulfur Compounds', 'Thiophenes']" +DB00285,Venlafaxine,"Venlafaxineis a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of major depression, generalized or social anxiety disorder, and panic disorder.","['P31645', 'P23975', 'Q01959']","Venlafaxine is an antidepressant agent that works to ameliorate the symptoms of various psychiatric disorders by increasing the level of neurotransmitters in the synapse. Venlafaxine does not mediate muscarinic, histaminergic, or adrenergic effects.17",COC1=CC=C(C=C1)C(CN(C)C)C1(O)CCCCC1,"The exact mechanism of action of venlafaxine in the treatment of various psychiatric conditions has not been fully elucidated; however, it is understood that venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) potently and selectively inhibits the reuptake of both serotonin and norepinephrine at the presynaptic terminal.,,This results in increased levels of neurotransmitters available at the synapse that can stimulate postsynaptic receptors.It is suggested that venlafaxine has a -fold selectivity for serotonin compared to norepinephrine: venlafaxine initially inhibits serotonin reuptake at low doses, and with higher doses, it inhibits norepinephrine reuptake in addition to serotonin.,Venlafaxine and ODV are also weak inhibitors of dopamine reuptake.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Amines', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'BCRP/ABCG2 Inducers', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cyclohexanes', 'Cyclohexanols', 'Cycloparaffins', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Ethylamines', 'Hexanols', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Uptake Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phenethylamines', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin and Noradrenaline Reuptake Inhibitors', 'Serotonin Modulators']" +DB00968,Methyldopa,"Methyldopais a centrally-acting alpha-2 adrenergic agonist used to manage hypertension alone or in combination with hydrochlorothiazide, and to treat hypertensive crises.","['P20711', 'P08913']","Antihypertensive effects of methyldopa are mostly mediated by its pharmacologically active metabolite, alpha-methylnorepinephrine, which works as an agonist at central inhibitory alpha-adrenergic receptors.11Stimulation of alpha-adrenergic receptors leads to decreased peripheral sympathetic tone and reduced arterial pressure.3Methyldopa causes a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine. Overall, methyldopa lowers both standing blood pressure and especially supine blood pressure, with infrequent symptomatic postural hypotension. Methyldopa also reduces plasma renin activity but has negligible effects on glomerular filtration rate, renal blood flow, or filtration fraction. It also has no direct effect on cardiac function but in some patients, a slowed heart rate may occur.11Following oral administration, blood-pressure-lowering effects are observed within 12 to 24 hours in most patients, and a maximum reduction in blood pressure occurs in 4 to 6 hours. Blood pressure returns to pre-treatment levels within 24 to 48 hours following drug discontinuation.11Following intravenous administration, the blood-pressure-lowering effects of methyldopa last for about 10 to 16 hours.4",C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O,"The exact mechanism of methyldopa is not fully elucidated; however, the main mechanisms of methyldopa involve its actions on alpha-adrenergic receptor and the aromatic L-amino acid decarboxylase enzyme, to a lesser extent. The sympathetic outflow is regulated by alpha (α)- adrenergic receptors and imidazoline receptors expressed on adrenergic neurons within the rostral ventrolateral medulla.Methyldopa is metabolized to α‐methylnorepinephrine via dopamine beta-hydroxylase activity and, consequently, alpha-methylepinephrine via phenylethanolamine-N-methyltransferase activity.,,Mediating the therapeutic effects of methyldopa, α‐methylnorepinephrine and α-methylepinephrine active metabolites are agonists at presynaptic alpha- adrenergic receptors in the brainstem. Stimulating alpha- adrenergic receptors results in the inhibition of adrenergic neuronal outflow and attenuation of norepinephrine release in the brainstem. Consequently, the output of vasoconstrictor adrenergic signals to the peripheral sympathetic nervous system is reduced, leading to a reduction in blood pressure.The L-isomer of alpha-methyldopa also reduces blood pressure by inhibiting aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase, which is an enzyme responsible for the syntheses of dopamine and serotonin.Inhibiting this enzyme leads to depletion of biogenic amines such as norepinephrine. However, inhibition of aromatic L-amino acid decarboxylase plays a minimal role in the blood-pressure‐lowering effect of methyldopa.,TargetActionsOrganismAAromatic-L-amino-acid decarboxylaseinhibitorHumansAAlpha-A adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents Causing Muscle Toxicity', 'Amines', 'Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Antiadrenergic Agents, Centrally Acting', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Aromatic L-amino Acid Decarboxylase Inhibitors', 'Autonomic Agents', 'Benzene Derivatives', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'Central alpha-2 Adrenergic Agonist', 'Central Alpha-agonists', 'COMT Substrates', 'Dihydroxyphenylalanine', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenols', 'Sympatholytics']" +DB00338,Omeprazole,"Omeprazoleis a proton pump inhibitor used to treat GERD associated conditions such as heartburn and gastric acid hypersecretion, and to promote healing of tissue damage and ulcers caused by gastric acid and H. pylori infection.","['P20648', 'P35869']","Effects on gastric acid secretionThis drug decreases gastric acid secretionLabel. After oral administration, the onset of the antisecretory effect of omeprazole is usually achieved within one hour, with the maximum effect occurring by 2 hours after administration. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four daysLabel.Effects on serum gastrinIn studies of 200 or more patients, serum gastrin levels increased during the first 1-2 weeks of daily administration of therapeutic doses of omeprazole. This occurred in a parallel fashion with the inhibition of acid secretion. No further increase in serum gastrin occurred with continued omeprazole administration. Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may lead to false positive results in diagnostic studies for neuroendocrine tumorsLabel.Enterochromaffin-like (ECL) cell effectsHuman gastric biopsy samples have been obtained from more than 3000 pediatric and adult patients treated with omeprazole in long-term clinical studies. The incidence of enterochromaffin-like cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia have been identified in these patients. These studies, however, are of insufficient in power and duration to draw conclusions on the possible influence of long-term administration of omeprazole in the development of any premalignant or malignant conditionsLabel.Other effectsSystemic effects of omeprazole in the central nervous system, cardiovascular and respiratory systems have not been found to date. Omeprazole, given in oral doses of 30 or 40 mg for 2-4 weeks, showed no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretinLabel.",COC1=CC2=C(C=C1)N=C(N2)S(=O)CC1=NC=C(C)C(OC)=C1C,"Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid).Omeprazole is a member of a class of antisecretory compounds, the substitutedbenzimidazoles, that stop gastric acid secretion by selective inhibition of theH+/K+ ATPaseenzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of theH+/K+ ATPasepump, inhibiting gastric acid secretion for up to hours. This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulusLabel.Mechanism of H. pylori eradicationPeptic ulcer disease (PUD) is frequently associated withHelicobacter pyloribacterial infection (NSAIDs). The treatment of H. pylori infection may include the addition of omeprazole or other proton pump inhibitors as part of the treatment regimenLabel,.H. pylorireplicates most effectively at a neutral pH. Acid inhibition in H. pylori eradication therapy, including proton-pump inhibitors such as omeprazole, raises gastric pH, discouraging the growth of H.pylori. It is generally believed that proton pump inhibitors inhibit theureaseenzyme, which increases the pathogenesis of H. pylori in gastric-acid related conditions.TargetActionsOrganismAPotassium-transporting ATPase alpha chain inhibitorHumansUAryl hydrocarbon receptoragonistHumans",[],"['2-Pyridinylmethylsulfinylbenzimidazoles', 'Acid Reducers', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'BCRP/ABCG2 Inhibitors', 'Benzimidazoles', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Enzyme Inhibitors', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Proton Pump Inhibitors', 'Proton-pump Inhibitors', 'Pyridines', 'Sulfoxides', 'Sulfur Compounds']" +DB00333,Methadone,Methadoneis an opioid analgesic indicated for management of severe pain that is not responsive to alternative treatments. Also used to aid in detoxification and maintenance treatment of opioid addiction.,"['P35372', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'P41143', 'P36544', 'P46098', 'P32297', 'P43681', 'P17787']","Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis (through binding to receptors in the pupillary muscles), sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. Like many basic drugs, methadone also enters mast cells and releases histamine by a non-immunological mechanism leading to flushing, pruritus, and urticaria, which can commonly be misattributed to an allergic reaction.Compared to other opioids, methadone has fewer active metabolites and therefore a lower risk of neuropsychiatric toxicity. This means that higher doses needed to manage severe pain or addiction are less likely to result in delirium, hyperalgesia, or seizures.19,20Similar to morphine, both methadone isomers are 5-HT(3) receptor antagonists, although l-methadone produces greater inhibition than d-methadone.Methadone's effects are reversible by naloxone with a pA2 value similar to its antagonism of morphine.21,22,23Dependence and ToleranceAs with other opioids, tolerance and physical dependence may develop upon repeated administration of methadone and there is a potential for development of psychological dependence. Physical dependence and tolerance reflect the neuroadaptation of the opioid receptors to chronic exposure to an opioid and are separate and distinct from abuse and addiction. Tolerance, as well as physical dependence, may develop upon repeated administration of opioids, and are not by themselves evidence of an addictive disorder or abuse.Patients on prolonged therapy should be tapered gradually from the drug if it is no longer required for pain control. Withdrawal symptoms may occur following abrupt discontinuation of therapy or upon administration of an opioid antagonist. Some of the symptoms that may be associated with abrupt withdrawal of an opioid analgesic include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.21,22,23Cardiac Conduction EffectsLaboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. These cases appear to be more commonly associated with, but not limited to, higher dose treatment (> 200 mg/day). Methadone should be administered with particular caution to patients already at risk for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia). Careful monitoring is recommended when using methadone in patients with a history of cardiac conduction disease, those taking medications affecting cardiac conduction, and in other cases where history or physical exam suggest an increased risk of dysrhythmia.21,22,23Respiratory Depression and OverdoseSerious, life-threatening, or fatal respiratory depression may occur with use of methadone. Patients should be +monitored for respiratory depression, especially during initiation of methadone or following a dose increase.Respiratory depression is of particular concern in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Methadone should be administered with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, and CNS depression or coma. In these patients, even usual therapeutic doses of methadone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Alternative, non-opioid analgesics should be considered, and methadone should be employed only under careful medical supervision at the lowest effective dose.Infants exposed in-utero or through breast milk are at risk of life-threatening respiratory depression upon delivery or when nursed.Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, in the short-term use setting. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration.21,22,23Head Injury and Increased Intracranial PressureThe respiratory depressant effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, opioids produce effects which may obscure the clinical course of patients with head injuries. In such patients, methadone must be used with caution, and only if it is deemed essential.21,22,23Incomplete Cross-tolerance between Methadone and other OpioidsPatients tolerant to other opioids may be incompletely tolerant to methadone. Incomplete cross-tolerance is of particular concern for patients tolerant to other µ-opioid agonists who are being converted to methadone, thus making the determination of dosing during opioid conversion complex. Deaths have been reported during conversion from chronic, high-dose treatment with other opioid agonists. A high degree of “opioid tolerance” does not eliminate the possibility of methadone overdose, iatrogenic or otherwise.21,22,23Crosstolerance between morphine and methadone has been demonstrated, as steady-state plasma methadone concentrations required for effectiveness (C50%) were higher in abstinent rats previously dosed with morphine, as compared to controls.Misuse, Abuse, and Diversion of OpioidsMethadone is a mu-agonist opioid with an abuse liability similar to morphine. Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion.Methadone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when dispensing Methadone in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion.21,22,23Hypotensive EffectThe administration of methadone may result in severe hypotension in patients whose ability to maintain normal blood pressure is compromised (e.g., severe volume depletion).21,22,23Gastrointestinal EffectsMethadone and other morphine-like opioids have been shown to decrease bowel motility and cause constipation. This primarily occurs through agonism of opioid receptors in the gut wall. Methadone may obscure the diagnosis or clinical course of patients with acute abdominal conditions.21,22,23Sexual Function/ReproductionReproductive function in human males may be decreased by methadone treatment. Reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals. In addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported. Long-term use of opioids may be associated with decreased sex hormone levels and symptoms such as low libido, erectile dysfunction, or infertility.21,22,23",CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1,"Methadone is a synthetic opioid analgesic with full agonist activity at the µ-opioid receptor. While agonism of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous systems. Interestingly, methadone differs frommorphine(which is considered the gold standard reference opioid) in its antagonism of the N-methyl-D-aspartate (NMDA) receptor and its strong inhibition of serotonin and norepinephrine uptake, which likely also contributes to its antinociceptive activity.Methadone is administered as a : racemic mixture of (R)- and (S)-stereoisomers, with (R)-methadone demonstrating ~-fold higher affinity and potency for the µ-opioid receptor than the (S) stereoisomer.The analgesic activity of the racemate is almost entirely due to the (R)-isomer, while the (S)-isomer lacks significant respiratory depressant activity but does have antitussive effects.While methadone shares similar effects and risks of other opioids such asmorphine,hydromorphone,oxycodone, andfentanylit has a number of unique pharmacokinetic and pharmacodynamic properties that distinguish it from them and make it a useful agent for the treatment of opioid addiction. For example, methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.TargetActionsOrganismAMu-type opioid receptoragonistHumansANMDA receptorantagonistHumansADelta-type opioid receptoragonistHumansANeuronal acetylcholine receptor subunit alpha-agonistHumansU-hydroxytryptamine receptor AantagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit beta-antagonistHumans","['Opioid Detoxification', 'Maintenance therapy']","['Analgesics', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antitussive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diphenylpropylamine Derivatives', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Addictive Disorders', 'Drugs Used in Opioid Dependence', 'High-risk opioids', 'Ketones', 'Moderate Risk QTc-Prolonging Agents', 'Narcotics', 'Nervous System', 'Nicotinic Antagonists', 'NMDA Receptor Antagonists', 'Opiate Agonists', 'Opioid Agonist', 'Opioids', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'QTc Prolonging Agents', 'Respiratory System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Thyroxine-binding globulin inducers']" +DB01233,Metoclopramide,"Metoclopramideis an antiemetic agent and dopamine D2 antagonist used in the treatment of gastroesophageal reflux disease, prevention of nausea and vomiting, and to stimulate gastric emptying.","['Q13639', 'P46098', 'P11229', 'P14416']","Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions.17,18,19Because of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks.4,18",CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC,"Metoclopramide causes antiemetic effects by inhibiting dopamine D and serotonin -HT receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain.,Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D receptors, agonism of serotonin -HT receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D receptors.,,TargetActionsOrganismA-hydroxytryptamine receptor agonistHumansA-hydroxytryptamine receptor AantagonistHumansAMuscarinic acetylcholine receptor MagonistHumansADopamine D receptorantagonistHumans","['Facilitation of small bowel intubation therapy', 'Gastric emptying for radiologic procedures']","['Acids, Carbocyclic', 'Agents Causing Muscle Toxicity', 'Alimentary Tract and Metabolism', 'Amides', 'Aminobenzoates', 'Antiemetics', 'Autonomic Agents', 'Benzamides and benzamide derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Chlorobenzoates', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs for Functional Gastrointestinal Disorders', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Hydroxybenzoates', 'Methemoglobinemia Associated Agents', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'para-Aminobenzoates', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'Prokinetic Agents', 'Propulsives', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00281,Lidocaine,Lidocaineis a local anesthetic used in a wide variety of superficial and invasive procedures.,"['Q9Y5Y9', 'Q15858', 'Q14524', 'P00533', 'P35499', 'P02763', 'P19652']","Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure10,7. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present10,7. The net effect is normally a modest hypotension when the recommended dosages are not exceeded10,7.In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction10,7,8. Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse10,7,8.Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base8. As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values8. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection7. The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection7.Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation8. This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels8.",CCN(CC)CC(=O)NC1=C(C)C=CC=C1C,"Lidocaine is a local anesthetic of the amide type,,. It is used to provide local anesthesia by nerve blockade at various sites in the body,,. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action,,. In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes,,. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions,,. The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization,,. As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential,,. This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place,,.In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system,,. After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction,,.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansUEpidermal growth factor receptorantagonistHumansUSodium channel protein type subunit alphaNot AvailableHumansUAlpha--acid glycoprotein Not AvailableHumansUAlpha--acid glycoprotein Not AvailableHumans","['Local Anaesthesia therapy', 'Post Myocardial Infarction Treatment', 'Regional Anesthesia therapy']","['Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Agents that reduce seizure threshold', 'Amides', 'Amines', 'Analgesics and Anesthetics', 'Anesthetics', 'Anesthetics for Topical Use', 'Anesthetics, Local', 'Anilides', 'Aniline Compounds', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ib', 'Antipruritics and Local Anesthetics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Cardiac Therapy', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Local Anesthesia', 'Local Anesthetics (Amide)', 'Membrane Transport Modulators', 'Methemoglobinemia Associated Agents', 'Nervous System', 'Neuraxial Anesthetics', 'Ophthalmologicals', 'Otologicals', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Sodium Channel Blockers', 'Throat Preparations', 'Vasoprotectives', 'Voltage-Gated Sodium Channel Blockers']" +DB01396,Digitoxin,"Digitoxinis a cardiac glycoside used in the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure.",['P05023'],"Digitoxin is a cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting (From Martindale, The Extra Pharmacopoeia, 30th ed, p665). It is eliminated hepatically making it useful in patients with poor or erratic kidney function, although it is now rarely used in practice. Digitoxin lacks the strength of evidence that digoxin has in the management of heart failure.",[H][C@@]1(CC[C@]2(O)[C@]3([H])CC[C@]4([H])C[C@H](CC[C@]4(C)[C@@]3([H])CC[C@]12C)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1)C1=CC(=O)OC1,"Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin also acts on the electrical activity of the heart, increasing the slope of phase depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-inhibitorHumans",[],"['Antiarrhythmic agents', 'Carbohydrates', 'Cardanolides', 'Cardenolides', 'Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Digitalis Glycosides', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Glycosides', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Potential QTc-Prolonging Agents', 'Protective Agents', 'QTc Prolonging Agents', 'Steroids']" +DB00390,Digoxin,Digoxinis a cardiac glycoside used in the treatment of mild to moderate heart failure and for ventricular response rate control in chronic atrial fibrillation.,['P05023'],"Digoxin is a positive inotropic and negative chronotropic drug7, meaning that it increases the force of the heartbeat and decreases the heart rate.23The decrease in heart rate is particularly useful in cases of atrial fibrillation, a condition characterized by a fast and irregular heartbeat.13The relief of heart failure symptoms during digoxin therapy has been demonstrated in clinical studies by increased exercise capacity and reduced hospitalization due to heart failure and reduced heart failure-related emergency medical visits.25Digoxin has a narrow therapeutic window.25A note on cardiovascular riskDigoxin poses a risk of rapid ventricular response that can cause ventricular fibrillation in patients with an accessory atrioventricular (AV) pathway. Cardiac arrest as a result of ventricular fibrillation is fatal.25An increased risk of fatal severe or complete heart block is present in individuals with pre-existing sinus node disease and AV block who take digoxin.25",[H][C@]12CC[C@]3([H])[C@]([H])(C[C@@H](O)[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1,"Digoxin exerts hemodynamic, electrophysiologic, and neurohormonal effects on the cardiovascular system.It reversibly inhibits the Na-K ATPase enzyme, leading to various beneficial effects. The Na-K ATPase enzyme functions to maintain the intracellular environment by regulating the entry and exit of sodium, potassium, and calcium (indirectly). Na-K ATPase is also known as thesodium pump. The inhibition of the sodium pump by digoxin increases intracellular sodium and increases the calcium level in the myocardial cells, causing an increased contractile force of the heart.,This improves the left ventricular ejection fraction (EF), an important measure of cardiac function.,Digoxin also stimulates the parasympathetic nervous system via the vagus nerveleading to sinoatrial (SA) and atrioventricular (AV) node effects, decreasing the heart rate.,Part of the pathophysiology of heart failure includes neurohormonal activation, leading to an increase in norepinephrine. Digoxin helps to decrease norepinephrine levels through activation of the parasympathetic nervous system.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-inhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Carbohydrates', 'Cardanolides', 'Cardenolides', 'Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Digitalis Glycosides', 'Digoxin and derivatives', 'Digoxin, immunology', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Fused-Ring Compounds', 'Glycosides', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Potential QTc-Prolonging Agents', 'Protective Agents', 'QTc Prolonging Agents']" +DB01426,Ajmaline,Ajmalineis an antiarrhythmic used to manage a variety of forms of tachycardias.,['Q14524'],"Ajmaline is a class 1A antiarrhythmic agent. By interfering with the sodium channels, this drug allows for improvement in abnormal rhythms of the heart",[H][C@]12C[C@]34[C@H](O)C1[C@@]1([H])C[C@]([H])(N2[C@H](O)[C@H]1CC)[C@]3([H])N(C)C1=CC=CC=C41,The class I antiarrhythmic agents interfere with the sodium channel. A class IA agent lengthens the action potential (right shift) which brings about improvement in abnormal heart rhythms. This drug in particular has a high affinity for the Nav . sodium channel.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans,['Persistent Ventricula'],"['Ajmaline and derivatives', 'Alkaloids', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ia', 'Antiarrhythmics, Class Ic', 'Cardiac Therapy', 'Cardiovascular Agents', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Membrane Transport Modulators', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Secologanin Tryptamine Alkaloids', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB00898,Ethanol,"A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages.","['P14867', 'Q8TCU5', 'P23415', 'P23416', 'Q02641', 'P46098', 'P47869', 'Q9GZZ6', 'Q13936', 'P31644', 'P48169', 'P34903', 'P42261', 'Q06432', 'Q15822', 'Q16445', 'P42262', 'P48058', 'P42263', 'P43681', 'P17787', 'P48549', 'P48051', 'P19320', 'Q99808', 'P48544', 'P36544', 'Q9UGM1', 'P18505', 'P28472', 'P47870', 'Q13698', 'Q01668', 'P30926', 'P32297', 'P30532', 'Q15825', 'Q05901', 'Q8N1C3', 'Q99928', 'P78334', 'O00591', 'Q9UN88', 'O14764', 'Q14542', 'A5X5Y0', 'O95264', 'Q70Z44', 'Q8WXA8', 'Q9Y698', 'Q92806', 'P32004', 'P22303', 'P40394']","Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.",CCO,"Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. +The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha and alpha subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGlutamate receptor ionotropic, NMDA AantagonistHumansAGlycine receptor subunit alpha-agonistHumansAGlycine receptor subunit alpha-agonistHumansUVoltage-dependent L-type calcium channel subunit beta-Not AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumansUGamma-aminobutyric acid receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUVoltage-dependent L-type calcium channel subunit alpha-CNot AvailableHumansUGamma-aminobutyric acid receptor subunit alpha-Not AvailableHumansUGamma-aminobutyric acid receptor subunit alpha-Not AvailableHumansUGamma-aminobutyric acid receptor subunit alpha-Not AvailableHumansUGlutamate receptor Not AvailableHumansUVoltage-dependent calcium channel gamma- subunitNot AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUGamma-aminobutyric acid receptor subunit alpha-Not AvailableHumansUGlutamate receptor Not AvailableHumansUGlutamate receptor Not AvailableHumansUGlutamate receptor Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumansUG protein-activated inward rectifier potassium channel Not AvailableHumansUG protein-activated inward rectifier potassium channel Not AvailableHumansUVascular cell adhesion protein Not AvailableHumansUEquilibrative nucleoside transporter Not AvailableHumansUG protein-activated inward rectifier potassium channel Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUGamma-aminobutyric acid receptor subunit beta-Not AvailableHumansUGamma-aminobutyric acid receptor subunit beta-Not AvailableHumansUGamma-aminobutyric acid receptor subunit beta-Not AvailableHumansUVoltage-dependent L-type calcium channel subunit alpha-SNot AvailableHumansUVoltage-dependent L-type calcium channel subunit alpha-DNot AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumansUGamma-aminobutyric acid receptor subunit gamma-Not AvailableHumansUGamma-aminobutyric acid receptor subunit gamma-Not AvailableHumansUGamma-aminobutyric acid receptor subunit epsilonNot AvailableHumansUGamma-aminobutyric acid receptor subunit piNot AvailableHumansUGamma-aminobutyric acid receptor subunit thetaNot AvailableHumansUGamma-aminobutyric acid receptor subunit deltaNot AvailableHumansUEquilibrative nucleoside transporter Not AvailableHumansU-hydroxytryptamine receptor ENot AvailableHumansU-hydroxytryptamine receptor BNot AvailableHumansU-hydroxytryptamine receptor DNot AvailableHumansU-hydroxytryptamine receptor CNot AvailableHumansUVoltage-dependent calcium channel gamma- subunitNot AvailableHumansUG protein-activated inward rectifier potassium channel Not AvailableHumansUNeural cell adhesion molecule LNot AvailableHumansUAcetylcholinesteraseactivatorHumansNAlcohol dehydrogenase class mu/sigma chainsubstrateHumans","['Hand Hygiene', 'Skin disinfection']","['Agents Causing Muscle Toxicity', 'Alcohols', 'Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Antidotes', 'Antiseptics and Disinfectants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (moderate)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Miscellaneous Local Anti-infectives', 'Miscellaneous Therapeutic Agents', 'Nerve Depressants', 'Neurotoxic agents', 'NMDA Receptor Antagonists', 'Solvents']" +DB00454,Meperidine,Meperidineis an opioid agonist with analgesic and sedative properties used to manage severe pain.,"['P41145', 'Q05586', 'Q13224', 'Q12879', 'Q14957', 'O15399', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P35372', 'Q01959', 'P23975', 'P31645', 'P23141']","Meperidine is a synthetic opiate agonist belonging to the phenylpiperidine class. Meperidine may produce less smooth muscle spasm, constipation, and depression of the cough reflex than equivalent doses of morphine. The onset of action is lightly more rapid than with morphine, and the duration of action is slightly shorter. The chemical structure of meperidine is similar to local anesthetics. Meperidine is recommended for relief of moderate to severe acute pain and has the unique ability to interrupt postoperative shivering and shaking chills induced by amphotericin B. Meperidine has also been used for intravenous regional anesthesia, peripheral nerve blocks and intraarticular, epidural and spinal analgesia. Meperidine is considered a second-line agent for the treatment of acute pain.",CCOC(=O)C1(CCN(C)CC1)C1=CC=CC=C1,"Meperidine is primarily a kappa-opiate receptor agonist and also has local anesthetic effects. Meperidine has more affinity for the kappa-receptor than morphine. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Opioids close N-type voltage-operated calcium channels (OP-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP and OP receptor agonist). This results in hyperpolarization and reduced neuronal excitability.TargetActionsOrganismAKappa-type opioid receptorNot AvailableHumansUGlutamate receptor ionotropic, NMDA antagonistHumansUGlutamate receptor ionotropic, NMDA BantagonistHumansUGlutamate receptor ionotropic, NMDA AantagonistHumansUGlutamate receptor ionotropic, NMDA CantagonistHumansUGlutamate receptor ionotropic, NMDA DantagonistHumansUMuscarinic acetylcholine receptorbinderHumansUMu-type opioid receptoragonistHumansUSodium-dependent dopamine transporterinhibitorHumansUSodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent serotonin transporterbinderHumansULiver carboxylesterase Not AvailableHumans","['Anesthesia therapy', 'Anesthetic premedication therapy', 'General Anesthesia', 'Local Anaesthesia therapy', 'Perioperative management therapy']","['Adjuvants', 'Adjuvants, Anesthesia', 'Agents that reduce seizure threshold', 'Analgesics', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'High-risk opioids', 'Isonipecotic Acids', 'Narcotics', 'Nervous System', 'NMDA Receptor Antagonists', 'Opiate Agonists', 'Opioid Agonist', 'Opioids', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenylpiperidine opioids', 'Piperidines', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB00182,Amphetamine,Amphetamineis a CNS stimulant and sympathomimetic agent indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).,"['Q05940', 'Q01959', 'Q16568', 'Q96RJ0', 'P21397', 'P27338', 'Q99870', 'P23975', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945', 'P14416', 'P27338', 'P31645']","From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce cardiovascular side effects.5There are old reports of a cognitive enhancement related to the administration of amphetamine in which improvements in intelligence test scores were reported.2In ADHD, amphetamine has been largely showed to produce remarkable improvements in school performance, behavior, and demeanor.1The effect was shown to be produced through both racemic forms and to this date, the use of racemic forms 3:1 (D:L) is very common.3The therapeutic effect of amphetamine on serotonin does not seem to have a significant clinical effect on ADHD as observed on comparative studies with amphetamine and fenfluramine, a powerful serotonin releasing factor. However, the indirect effect on serotonin might have an effect on the depression and anxiety profile of ADHD.6Studies regarding the illicit use of amphetamine in which heavy consumers were studied proved the generation of a paranoid state which flagged this drug as a psychiatric danger compound.13This observation was supported by the continuous reports of misuse in patients under depression.1",CC(N)CC1=CC=CC=C1,"It is important to consider that amphetamine has a very similar structure to the catecholamine neurotransmitters mainly on the presence of a long planar conformation, the presence of an aromatic ring and nitrogen in the aryl side chain. Amphetamine, as well as other catecholamines, is taken into presynaptic nerve terminals by the association with two sodium ions and one chloride ion. The complex of the amphetamine with the ions is actively transported by monoamine reuptake transporters. As amphetamine acts competitively with the endogenous monoamines, the greater the number of amphetamines the more internalized amphetamine will be found.Once inside the presynaptic terminal, amphetamine displaces other monoamines to be stored by VMAT which produces the pumping of the neurotransmitters into the synapse by a process called retro-transport.This process of release of neurotransmitters is approximately fourfold more potent in the d-isomer for the release of dopamine.The mechanism of action of amphetamine is complemented by the inhibition of the reuptake and of monoamine oxidase which acts synergistically to produce a significant increase the monoamine concentration.This activity is not done as an inhibitor per se but more as a competitive substrate and thus, amphetamine is known to be a weak dopamine reuptake inhibitor, moderate noradrenaline reuptake inhibitor and very weak serotonin reuptake inhibitor. From this specific action, the l-isomer is known to be significantly less potent.Lastly, amphetamine is known to be an inhibitor of the mitochondrial-bound enzyme MAO which is the catalytic enzyme in charge of degrading all the excess of neurotransmitters. This mechanism of action is often overpassed as amphetamine is a weak MAO inhibitor but this mechanism cannot be dismissed.TargetActionsOrganismASynaptic vesicular amine transporterinhibitorHumansASodium-dependent dopamine transporternegative modulatorHumansACocaine- and amphetamine-regulated transcript proteinagonistHumansATrace amine-associated receptor agonistHumansAMonoamine oxidaseinhibitorHumansAvesicular monoamine transporter (VMAT)Not AvailableHumansUSodium-dependent noradrenaline transporteragonistsubstrateHumansUAlpha adrenergic receptoragonistHumansUBeta adrenergic receptoragonistHumansUDopamine D receptorbinderHumansUAmine oxidase [flavin-containing] BinhibitorHumansUSodium-dependent serotonin transporterbinderHumans",[],"['Adrenergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Amines', 'Amphetamines', 'Autonomic Agents', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Catechols', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Centrally Acting Sympathomimetics', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Phenols', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetics']" +DB01202,Levetiracetam,"Levetiracetamis a novel anticonvulsant agent used as an adjunct medication to manage partial onset, myoclonic, and generalized tonic-clonic seizures in patients with epilepsy.","['Q00975', 'Q7L0J3']","Levetiracetam appears to prevent seizure activity via the selective inhibition of hypersynchronized epileptiform burst firing without affecting normal neuronal transmission, though the exact mechanism through which this occurs is unclear.11,15The therapeutic index of levetiracetam is wide,15,9making it relatively unique amongst other anti-epileptic medications.Anti-epileptic drugs, including levetiracetam, may increase the risk of suicidal ideation or behaviour - patients taking levetiracetam should be monitored for the emergence or worsening of depressive symptoms, suicidal ideation, and behavioural abnormalities.11,13,15",CC[C@H](N1CCCC1=O)C(N)=O,"The exact mechanism through which levetiracetam exerts its anti-epileptic effects is unclear, but is thought to be unique amongst other anti-epileptic medications. Current knowledge suggests that levetiracetam’s binding to synaptic vesicle protein A (SVA) is a key driver of its action. SVA is a membrane-bound protein that is found on synaptic vesicles and is ubiquitous throughout the CNS- it appears to play a role in vesicle exocytosis,and in the modulation of synaptic transmission by increasing the available amount of secretory vesicles available for neurotransmission.Stimulation of pre-synaptic SVA by levetiracetam may inhibit neurotransmitter release,but this action does not appear to affect normal neurotransmission. This has led to the suggestion that levetiracetam exclusively modulates the function of SVA only under pathophysiological conditions.Levetiracetam and related analogues showed a correlation between affinity for SVA and anti-epileptic potency, further suggesting that action at this site contributes to the anti-epileptic activity of the drug.,Levetiracetam has also been shown to indirectly affect GABAergic neurotransmission (despite having no direct effect on GABAergic or glutamatergic receptors) and modulate ionic currents.Similarly, levetiracetam has been shown in vitro to inhibit N-type calcium channels.How, or even if, these actions are implicated in its anti-epileptic action have yet to be elucidated.TargetActionsOrganismAVoltage-dependent N-type calcium channel subunit alpha-BinhibitorHumansASynaptic vesicle glycoprotein AagonistHumans",[],"['Acetamides', 'Amides', 'Anticonvulsants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Miscellaneous Anticonvulsants', 'Nervous System', 'P-glycoprotein substrates', 'Pyrrolidines', 'Pyrrolidinones']" +DB00949,Felbamate,Felbamateis an anticonvulsant used to treat severe epilepsy.,"['Q13224', 'Q12879']","Felbamate is an antiepileptic indicated as monotherapy or as an adjunct to other anticonvulsants for the treatment of partial seizures resulting from epilepsy. Receptor-binding studiesin vitroindicate that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex. However, felbamate does interact as an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex.",NC(=O)OCC(COC(N)=O)C1=CC=CC=C1,"The mechanism by which felbamate exerts its anticonvulsant activity is unknown, but in animal test systems designed to detect anticonvulsant activity, felbamate has properties in common with other marketed anticonvulsants.In vitroreceptor binding studies suggest that felbamate may be an antagonist at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. Antagonism of the NMDA receptor glycine binding site may block the effects of the excitatory amino acids and suppress seizure activity. Animal studies indicate that felbamate may increase the seizure threshold and may decrease seizure spread. It is also indicated that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding.TargetActionsOrganismAGlutamate receptor ionotropic, NMDA BantagonistHumansAGlutamate receptor ionotropic, NMDA AantagonistHumans",[],"['Acids, Acyclic', 'Alcohols', 'Anti-epileptic Agent', 'Anticonvulsants', 'Carbamates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Excitatory Amino Acid Agents', 'Excitatory Amino Acid Antagonists', 'Glycols', 'Nervous System', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'Phenylcarbamates', 'Potential QTc-Prolonging Agents', 'Propylene Glycols', 'QTc Prolonging Agents']" +DB00860,Prednisolone,"Prednisoloneis a glucocorticoid used to treat adrenocortical insufficiency, inflammatory conditions, and some cancers.",['P04150'],"Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.4Prednisolone has a short duration of action as the half life is 2.1-3.5 hours.1Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces.4Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.4",[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Alimentary Tract and Metabolism', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antidotes', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids Acting Locally', 'Corticosteroids for Local Oral Treatment', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Weak (Group I)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'Nasal Preparations', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Otologicals', 'P-glycoprotein substrates', 'Prednisolone and Prodrugs', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Sensory Organs', 'Steroids', 'Stomatological Preparations', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Vasoprotectives']" +DB01041,Thalidomide,"Thalidomideis a medication used to treat cancers, particularly newly diagnosed multiple myeloma, and erythema nodosum leprosum.","['Q96SW2', 'P02763', 'P19652']","Thalidomide, originally developed as a sedative, is an immunomodulatory and anti-inflammatory agent with a spectrum of activity that is not fully characterized. However, thalidomide is believed to exert its effect through inhibiting and modulating the level of various inflammatory mediators, particularly tumor necrosis factor-alpha (TNF-a) and IL-6.5Additionally, thalidomide is also shown to inhibit basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), suggesting a potential anti-angiogenic application of thalidomide in cancer patients.6Thalidomide is racemic — it contains both left and right handed isomers in equal amounts: the (+)R enantiomer is effective against morning sickness, and the (−)S enantiomer is teratogenic. The enantiomers are interconverted to each other in vivo; hence, administering only one enantiomer will not prevent the teratogenic effect in humans7.",O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12,"The mechanism of action of thalidomide is not fully understood. Previous research indicate that thalidomide binds to cerebron, a component of the E ubiquitin ligase complex, to selectively degrade the transcription factor IKZF and IKZF. These transcription factors are vital for the proliferation and survival of malignant myeloma cells.Regarding TNF-alpha, thalidomide seems to block this mediator via a variety of mechanism. Thalidomide can inhibit the expression myeloid differentiating factor (MyD), an adaptor protein that is involved in the TNF-alpha production signalling pathway, at the protein and RNA level. Additionally, thalidomide prevents the activation of Nuclear Factor Kappa B (NF-kB), another upstream effector of the TNF-alpha production pathway. Finally, some evidences suggest that thalidomide can block alpha- acid glycoprotein (AGP), a known inducer of the NF-kB/MyD pathway, thus inhibiting the expression of TNF-alpha. The down-regulation of NF-kB and MyD can also affect the cross talk between the NF-kB/MyD and VEGF pathway, resulting in thalidomide's anti-angiogenic effect.TargetActionsOrganismAProtein cerebloninhibitorHumansADNAintercalationHumansAalpha-acid glycoproteinbinderHumans",[],"['Angiogenesis Inhibitors', 'Angiogenesis Modulating Agents', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Growth Inhibitors', 'Growth Substances', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Immunologic Factors', 'Immunomodulatory Agents', 'Immunosuppressive Agents', 'Isoindoles', 'Leprostatic Agents', 'Myelosuppressive Agents', 'Noxae', 'Photosensitizing Agents', 'Phthalimides', 'Teratogens', 'Toxic Actions', 'Tumor Necrosis Factor Blockers']" +DB00915,Amantadine,"Amantadineis a medication used to treat dyskinesia in Parkinson's patients receiving levodopa, as well as extrapyramidal side effects of medications.","['P21430', 'Q8TCU5', 'P14416', 'P36544', 'P43681', 'P32297']","Amantadine is an antiviral drug which also acts as an antiparkinson agent, for which it is usually combined with L-DOPA when L-DOPA responses decline (probably due to tolerance). It is a derivate of adamantane, like a similar drug rimantadine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. It has been shown to cause an increase in dopamine release in the animal brain, and does not possess anticholinergic activity.",NC12CC3CC(CC(C3)C1)C2,"The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. It also has NMDA receptor antagonistic effects. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M (an ion channel), which is needed for the viral particle to become ""uncoated"" once it is taken inside the cell by endocytosis.TargetActionsOrganismAMatrix protein inhibitorInfluenza A virus (strain A/Ann Arbor// HN)AGlutamate receptor ionotropic, NMDA AantagonistHumansADopamine D receptoragonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumans",[],"['Adamantane Derivatives', 'Adamantanes', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Dyskinesia Agents', 'Anti-Infective Agents', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Antiviral Agents', 'Bridged-Ring Compounds', 'Central Nervous System Agents', 'Dopamine Agents', 'Drugs that are Mainly Renally Excreted', 'Influenza A M2 Protein Inhibitor', 'M2 Protein Inhibitors', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'NMDA Receptor Antagonists', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00584,Enalapril,Enalaprilis a prodrug of an ACE inhibitor used to treat hypertension and congestive heart failure.,['P12821'],"Enalapril is an antihypertensive agent that exhibits natriuretic and uricosuric properties. Enalapril lowers blood pressure in all grades of essential and renovascular hypertension, and peripheral vascular resistance without causing an increase in heart rate.6Individuals with low-renin hypertensive population were still responsive to enalapril.LabelThe duration of hypertensive effect in the systolic and diastolic blood pressure persists for at least 24 hours following initial administration of a single oral dose, and repeated daily administration of enalapril confers an additional reduction in blood pressure and a steady-state antihypertensive response may take several weeks.7In patients with severe congestive heart failure and inadequate clinical response to conventional antihypertensive therapies, treatment with enalapril resulted in improvements in cardiac performance as observed by a reduction in both preload and afterload, and improved clinical status long-term.6Furthermore, enalapril was shown to increase cardiac output and stroke volume while decreasing pulmonary capillary wedge pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. In clinical studies, enalapril reduced left ventricular mass, and did not affect cardiac function or myocardial perfusion during exercise.5Enalapril is not highly associated with the risk of bradycardia unlike most diuretics and beta-blockers6and it does not produce rebound hypertension upon discontinuation of therapy.5Enalapril is not reported to produce hypokalaemia, hyperglycaemia, hyperuricaemia or hypercholesterolaemia. In the kidneys, enalapril was shown to increase renal blood flow and decrease renal vascular resistance. It also augmented the glomerular filtration rate in patients with a glomerular filtration rate less than 80 mL/min.5When used in combination, enalapril was shown to attenuate the extent of drug-induced hypokalemia caused by hydrochlorothiazide6and the antihypertensive effects of both drugs were potentiated.2",CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O,"The renin-angiotensin-aldosterone system (RAAS) is a signaling pathway that works in synergism with the sympathetic system to regulate blood pressure and fluid and electrolyte homeostasis. Activation of this system upon stimulation by different factors, such as low blood pressure and nerve impulses, leads to increased release of norepinephrine (NE) from sympathetic nerve terminals and effects on the vascular growth, vasoconstriction, and salt retention in the kidneys.Renin is released from +Renin acts on the precursor prottein angiotensinogen, which is a plasma globulin synthesized from the liver, to produce cleaved peptide hormone angiotensin I.Angiotensin I then can be further cleaved by ACE to produce angiotensin II, a vasoconstrictive peptide hormone.LabelPresent in different isoforms, angiotensin converting enzyme (ACE) is peptidyl dipeptidase enzyme expressed in various tissues, including the vascular tissues, such as the heart, brain, and kidneys.ACE also plays a role in inactivation of bradykinin, a potent vasodepressor peptide.,LabelAngiotensin II mediates various actions on the body by working on its G-protein coupled receptors, AT and AT.It causes direct vasoconstriction of precapillary arterioles and postcapillary venules, inhibits the reuptake of NE thereby increasing available levels, stimulates the release of catecholamines from the adrenal medulla, reduces urinary excretion of sodium ions and water by promoting proximal tubular reabsorption, stimulates synthesis and release of aldosterone from the adrenal cortex, and stimulates hypertrophy of both vascular smooth muscle cells and cardiac myocytes.Enalapril is a pharmacologically inactive prodrug that requires hepatic biotransformation to formenalaprilat, its active metabolite that works on the RAAS to inhibit ACE.LabelBiotransformation is critial for the therapeutic actions of the drug, as enalapril itself is only a weak inhibitor of ACE.ACE inhibition results in reduced production and plasma levels of angiotensin II, increased plasma renin activity due to the loss of feedback inhibition by angiotensin II, and decreased aldosterone secretion.However, plasma aldosterone levels usually return to normal during long-term administration of enalapril.Decreased levels of angiotensin II subsequently leads to the dilatation of peripheral vessles and reduced vascular resistance which in turn lower blood pressure.While inhibition of ACE leading to suppression of RAAS is thought to be the primary mechanism of action of enalapril, the drug was shown to still exert antihypertensive effects on individuals with low-renin hypertension. It is suggested that enalapril may mediate its pharmacological actions via other modes of action that are not fully understood.LabelAs ACE is structurally similar to kininase I, which is a carboxypeptidase that degrades bradykinin, whether increased levels of bradykinin play a role in the therapeutic effects of enalapril remains to be elucidated.LabelTargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Amino Acids, Peptides, and Proteins', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Decreased Blood Pressure', 'Dipeptides', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hypotensive Agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'Oligopeptides', 'P-glycoprotein inhibitors', 'Peptides', 'Photosensitizing Agents', 'Protease Inhibitors']" +DB01118,Amiodarone,Amiodaroneis a class III antiarrhythmic indicated for the treatment of recurrent hemodynamically unstable ventricular tachycardia and recurrent ventricular fibrillation.,"['Q12809', 'Q9H252', 'Q9NS40', 'P08588', 'P07550', 'P13945', 'Q9P0X4', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'P10827', 'P10828', 'P37231', 'Q07869', 'Q86YN6']","After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias.2,7,18When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival.18Amiodarone prolongs the QRS duration and QT interval. In addition, a decreased SA (sinoatrial) node automaticity occurs with a decrease in AV node conduction velocity. Ectopic pacemaker automaticity is also inhibited.19Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.11",CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2,"Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms.,Unique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP).In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs.,Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.TargetActionsOrganismAHERG human cardiac K+ channelinhibitorHumansABeta adrenergic receptorinhibitordownregulatorHumansUVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansUVoltage gated L-type calcium channelinhibitorHumansUThyroid hormone receptorantagonistbinderHumans and other mammalsUPeroxisome proliferator-activated receptor gammaagonistHumansUPeroxisome proliferator-activated receptor alphaagonistHumansUPeroxisome proliferator-activated receptor gamma coactivator -betaagonistHumans",[],"['Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'alpha-Galactosidase, antagonists & inhibitors', 'Antiarrhythmic agents', 'Antiarrhythmics, Class III', 'Benzofurans', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Calcium Channel Blockers', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'OCT2 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Potassium Channel Blockers', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Vasodilating Agents']" +DB01136,Carvedilol,"Carvedilolis a non selective beta-adrenergic antagonist used to treat mild to severe chronic heart failure, hypertension, and left ventricular dysfunction following myocardial infarction in clinically stable patients.","['P08588', 'P35348', 'P35348', 'P35368', 'P25100', 'O95298', 'P07550', 'P15692', 'P16860', 'P17302', 'Q12809', 'P19320', 'P25100', 'P35368', 'P18825', 'P18089', 'P08913', 'P16581', 'Q16665', 'P48050', 'P63252']","Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism.5,6It has a long duration of action as it is generally taken once daily and has a broad therapeutic index as patients generally take 10-80mg daily.5,6Patients taking carvedilol should not abruptly stop taking this medication as this may exacerbate coronary artery disease.5,6",COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2,"Carvedilol inhibits exercise induce tachycardia through its inhibition of beta adrenoceptors.Carvedilol's action on alpha- adrenergic receptors relaxes smooth muscle in vasculature, leading to reduced peripheral vascular resistance and an overall reduction in blood pressure.,At higher doses, calcium channel blocking and antioxidant activity can also be seen.The antioxidant activity of carvedilol prevents oxidation of low density lipoprotein and its uptake into coronary circulation.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansAAlpha-A adrenergic receptorantagonistpotentiatorHumansAAlpha- adrenergic receptorsinhibitorHumansUNADH dehydrogenase [ubiquinone] subunit CinhibitorHumansUBeta- adrenergic receptorantagonistHumansUVascular endothelial growth factor AotherHumansUNatriuretic peptides BotherHumansUGap junction alpha- proteinotherHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUVascular cell adhesion protein inhibitorHumansUAlpha-D adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUE-selectininhibitorHumansUHypoxia-inducible factor -alphamodulatorHumansUInward rectifier potassium channel inhibitorHumansUInward rectifier potassium channel inhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Adrenergic beta2-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Alpha and Beta Blocking Agents', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Antioxidants', 'Biological Factors', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Carbazoles', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Indoles', 'Membrane Transport Modulators', 'Negative Inotrope', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Propanolamines', 'Propanols', 'Protective Agents', 'UGT1A1 Substrates', 'UGT2B7 substrates', 'Vasodilating Agents']" +DB00148,Creatine,"An amino acid derivative that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine.","['P06732', 'P12532', 'P12277', 'P17540', 'P48029', 'Q14353']","Creatine is a essential, non-proteinaceous amino acid derivative found in all animals. It is synthesized in the kidney, liver, and pancreas from L-arginine, glycine and L-methionine. Following its biosynthesis, creatine is transported to the skeletal muscle, heart, brain and other tissues. Most of the creatine is metabolized in these tissues to phosphocreatine (creatine phosphate). Phosphocreatine is a major energy storage form in the body. Supplemental creatine may have an energy-generating action during anaerobic exercise and may also have neuroprotective and cardioprotective actions.",CN(CC(O)=O)C(N)=N,"In the muscles, a fraction of the total creatine binds to phosphate - forming creatine phosphate. The reaction is catalysed by creatine kinase, and the result is phosphocreatine (PCr). Phosphocreatine binds with adenosine diphosphate to convert it back to ATP (adenosine triphosphate), an important cellular energy source for short term ATP needs prior to oxidative phosphorylation.TargetActionsOrganismACreatine kinase M-typeligandHumansACreatine kinase U-type, mitochondrialligandHumansACreatine kinase B-typeligandHumansACreatine kinase S-type, mitochondrialligandHumansASodium- and chloride-dependent creatine transporter Not AvailableHumansAGuanidinoacetate N-methyltransferaseproduct ofHumans",[],"['Amidines', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Dietary Supplements', 'Guanidines', 'Supplements']" +DB00583,Levocarnitine,Levocarnitineis a quaternary ammonium compound used to treat carnitine deficiency or to stimulate gastric and pancreatic secretions in hyperlipoproteinemia.,"['P47989', 'P23141', 'P05164', 'P50416', 'Q9H015', 'O76082', 'P43155', 'Q8N8R3', 'O43772', 'Q9UKG9', 'P23786']","Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The ""vitamin BT"" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.",C[N+](C)(C)C[C@H](O)CC([O-])=O,"Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases.TargetActionsOrganismUXanthine dehydrogenase/oxidaseNot AvailableHumansULiver carboxylesterase Not AvailableHumansUMyeloperoxidaseNot AvailableHumansUCarnitine O-palmitoyltransferase , liver isoformactivatorHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUCarnitine O-acetyltransferaseNot AvailableHumansUMitochondrial carnitine/acylcarnitine carrier protein CACLNot AvailableHumansUMitochondrial carnitine/acylcarnitine carrier proteinNot AvailableHumansUPeroxisomal carnitine O-octanoyltransferaseNot AvailableHumansUCarnitine O-palmitoyltransferase , mitochondrialNot AvailableHumans",[],"['Alimentary Tract and Metabolism', 'Amines', 'Amino Acids and Derivatives', 'Caloric Agents', 'Carnitine Analog', 'Dietary Supplements', 'Drugs that are Mainly Renally Excreted', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Inhibitors', 'Quaternary Ammonium Compounds', 'Supplements', 'Trimethyl Ammonium Compounds']" +DB00641,Simvastatin,Simvastatinis an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular events including myocardial infarction and stroke.,"['P04035', 'P20701', 'Q92769']","Simvastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.3,4Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.3Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.6,7,8,9,10Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.3,4Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.11,12Skeletal Muscle EffectsSimvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may also be at increased risk for myopathy. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued.29,30In a clinical trial database of 41,413 patients, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively, while the risk of myopathy with simvastatin 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. It's therefore recommended that the 80mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. As well, patients already stabilized on simvastatin 80mg should be monitored closely for evidence of muscle toxicity; if they need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potential for the drug-drug interaction.29,30The risk of myopathy during treatment with simvastatin may be increased with concurrent administration of interacting drugs such asfenofibrate,niacin,gemfibrozil,cyclosporine, and strong inhibitors of the CYP3A4 enzyme. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered withcolchicine, and caution should therefore be exercised when prescribing these two medications together.29,30Liver Enzyme AbnormalitiesPersistent increases (to more than 3X the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms.29,30In the Scandinavian Simvastatin Survival Study (4S),14the number of patients with more than one transaminase elevation to >3 times the ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14 [0.7%] vs. 12 [0.6%]). The frequency of single elevations of ALT to 3 times the ULN was significantly higher in the simvastatin group in the first year of the study (20 vs. 8, p=0.023), but not thereafter. In the HPS (Heart Protection Study),10in which 20,536 patients were randomized to receive simvastatin 40 mg/day or placebo, the incidences of elevated transaminases (>3X ULN confirmed by repeat test) were 0.21% (n=21) for patients treated with simvastatin and 0.09% (n=9) for patients treated with placebo.29,30Endocrine EffectsIncreases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.29Although cholesterol is the precursor of all steroid hormones, studies with simvastatin have suggested that this agent has no clinical effect on steroidogenesis. Simvastatin caused no increase in biliary lithogenicity and, therefore, would not be expected to increase the incidence of gallstones.30",[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC,"Simvastatin is a prodrug in which the -membered lactone ring of simvastatin is hydrolyzedin vivoto generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis.Simvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Simvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL).,The overall effect is a decrease in plasma LDL and VLDL.At therapeutic doses, the HMG-CoA enzyme is not completely blocked by simvastatin activity, thereby allowing biologically necessary amounts of mevalonate to remain available. As mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with simvastatin would also not be expected to cause any accumulation of potentially toxic sterols. In addition, HMG-CoA is metabolized readily back to acetyl-CoA, which participates in many biosynthetic processes in the body.In vitro and in vivo animal studies also demonstrate that simvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.Statins have also been found to bind allosterically to β integrin function-associated antigen- (LFA-), which plays an important role in leukocyte trafficking and in T cell activation.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUIntegrin alpha-Linhibitory allosteric modulatorHumansUHistone deacetylase inhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Naphthalenes', 'Noxae', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB01181,Ifosfamide,"Ifosfamideis an alkylating and immunosuppressive agent used in chemotherapy for the treatment of cancers, including testicular cancer, ovarian cancer, cervical cancer, osteocarcinoma, bladder cancer, small cell lung cancer, and non-Hodgkin's lymphoma.",['O75469'],"Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase nonspecific.",ClCCNP1(=O)OCCCN1CCCl,"The exact mechanism of ifosfamide has not been determined, but appears to be similar to other alkylating agents. Ifosfamide requires biotransformation in the liver by mixed-function oxidases (cytochrome P system) before it becomes active. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily through the alkylation of DNA, done by attaching the N- position of guanine to its reactive electrophilic groups. The formation of inter and intra strand cross-links in the DNA results in cell death.TargetActionsOrganismADNAother/unknownHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hydrocarbons, Halogenated', 'Immunosuppressive Agents', 'Methemoglobinemia Associated Agents', 'Mustard Compounds', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nitrogen Mustard Analogues', 'Nitrogen Mustard Compounds', 'Noxae', 'Organophosphorus Compounds', 'Oxazines', 'Phosphoramide Mustards', 'Phosphoramides', 'Toxic Actions']" +DB00091,Cyclosporine,"Cyclosporineis a steroid-sparing immunosuppressant used in organ and bone marrow transplants as well as inflammatory conditions such as ulcerative colitis, rheumatoid arthritis, and atopic dermatitis.","['P49069', 'Q96LZ3', 'P62937', 'P30405']","Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants.26This drug prevents and controls serious immune-mediated reactions including allograft rejection, graft versus host disease, and inflammatory autoimmune disease.26Some notable effects of cyclosporine are hypertrichosis, gingival hyperplasia, and hyperlipidemia. There is also some debate about this drug causing nephrotoxicity.9",CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C,"Cyclosporine is a calcineurin inhibitor that inhibits T cell activation.,,Its binding to the receptor cyclophilin- inside cells produces a complex known as cyclosporine-cyclophilin. This complex subsequently inhibits calcineurin, which in turn stops the dephosphorylation as well as the activation of the nuclear factor of activated T cells (NF-AT) that normally cause inflammatory reactions. NF-AT is a transcription factor that promotes the production of cytokines such as IL-, IL-, interferon-gamma and TNF-alpha, all of which are involved in the inflammatory process. Specifically, the inhibition of IL-, which is necessary for T cell activation or proliferation, is believed to be responsible for cyclosporine's immunosuppressive actions.,In addition to the above, the inhibition of NF-AT leads to lower levels of other factors associated with T helper cell function and thymocyte development.TargetActionsOrganismACalcium signal-modulating cyclophilin ligandbinderHumansACalcineurin subunit B type inhibitorHumansAPeptidyl-prolyl cis-trans isomerase AinhibitorbinderHumansAPeptidyl-prolyl cis-trans isomerase F, mitochondrialbinderHumans",[],"['Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Agents that produce hypertension', 'Agents that produce neuromuscular block (indirect)', 'Agents that reduce seizure threshold', 'Amino Acids, Peptides, and Proteins', 'Anti-Inflammatory Agents', 'Antirheumatic Agents', 'BCRP/ABCG2 Inhibitors', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Calcineurin Inhibitor Immunosuppressant', 'Calcineurin Inhibitors', 'Cyclosporins', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Immunologic Factors', 'Immunosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'Neurotoxic agents', 'NTCP Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 inhibitors', 'Ophthalmologicals', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Peptides', 'Peptides, Cyclic']" +DB00635,Prednisone,Prednisoneis a corticosteroid used to treat inflammation or immune-mediated reactions and to treat endocrine or neoplastic diseases.,['P04150'],"Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.1Prednisone has a short duration of action as the half life is 2-3 hours.9Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces.1Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.1",[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Prednisone is first metabolized in the liver to its active form, prednisolone, a glucocorticoid agonist corticosteroid.The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",['Palliative Treatment'],"['Adrenal Cortex Hormones', 'Adrenals', 'Alimentary Tract and Metabolism', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids Acting Locally', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Prednisolone and Prodrugs', 'Pregnadienediols', 'Pregnadienes', 'Pregnanes', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroxine-binding globulin inhibitors']" +DB01080,Vigabatrin,Vigabatrinis an irreversible GABA transaminase inhibitor used as an adjunct therapy to treat refractory complex partial seizures in patients ≥2 years unresponsive to alternatives. May also be used as monotherapy to treat infantile spasms in infants 1 month to 2 years.,['P80404'],"Vigabatrin is an antiepileptic agent chemically unrelated to other anticonvulsants. Vigabatrin prevents the metabolism of GABA by irreversibly inhibiting GABA transaminase (GABA-T). As vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), its duration of effect is thought to be dependent on the rate of GABA-T re-synthesis rather than on the rate of drug elimination.7",NC(CCC(O)=O)C=C,"Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter throughout the central nervous system, and the potentiation of GABAergic neurotransmission is therefore a crucial mechanism through which antiepileptic agents may combat the pathologic excitatory neurotransmission seen in epilepsy.Vigabatrin increases concentrations of GABA in the central nervous system by irreversibly inhibiting the enzymes responsible for its metabolism to succinic semialdehyde: gamma-aminobutyric acid transaminase (GABA-T).TargetActionsOrganismA-aminobutyrate aminotransferase, mitochondrialinhibitorHumans",[],"['Acids, Acyclic', 'Aminobutyrates', 'Anti-epileptic Agent', 'Anticonvulsants', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Enzyme Inhibitors', 'Fatty Acid Derivatives', 'Fatty Acids', 'GABA Agents', 'Lipids', 'Miscellaneous Anticonvulsants', 'Nervous System', 'Neurotransmitter Agents']" +DB01440,gamma-Hydroxybutyric acid,"Gamma hydroxybutyric acid, commonly abbreviated GHB, is a therapeutic drug which is illegal in multiple countries. It is currently regulated in the US and sold by Jazz Pharmaceuticals under the name Xyrem. However, it is important to note that GHB is a designated Orphan drug (in 1985). Today Xyrem is a Schedule III drug; however GHB remains a Schedule I drug and the illicit use of Xyrem falls under penalties of Schedule I. GHB is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits and almost all other living creatures in small amounts. It is used illegally under the street names Juice, Liquid Ecstasy or simply G, either as an intoxicant, or as a date rape drug. Xyrem is a central nervous system depressant that reduces excessive daytime sleepiness and cataplexy in patients with narcolepsy.","['Q9HAB3', 'P18505']","GHB predominantly works at two distinct binding sites in the central nervous system: it works as an agonist at the newly-characterized excitatory GHB receptor, while acting as a weak agonist at the inhibitory GABAB receptor. Since it is a naturally occurring substance, its physiological action is similar to that of some endogenous neurotransmitters in mammalian brain. GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire.",OCCCC(O)=O,"GHB is present at much higher concentrations in the brain, where it activates GABA-B receptors to exert its sedative effects. With high affinity, GHB binds to excitatory GHB receptors that are densely expressed throughout the brain, including the cotex and hippocampus. There is some evidence in research that upon activation of GHB receptors in some brain areas, the excitatory neurotransmitter glutamate is released. GHB stimulates dopamin release at low concentrations by acting on the GHB receptor, and the release of dopamine occurs in a biphasic manner. At higher concentrations, GHB inhibits dopamine release by acting on the GABA-B receptors, which is followed by GHB receptor signaling and increased release of dopamine. This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called ""rebound"" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. It is proposed that overtime, the level of GHB in the brain decreases below the threshold for significant GABA-B receptor activation, leading to preferential activation of GHB receptor over GABA-B receptors and enhanced wakefulness.TargetActionsOrganismAGamma-hydroxybutyrate (GHB) receptoragonistHumansAGamma-aminobutyric acid receptor subunit beta-agonistHumans",[],"['Acids, Acyclic', 'Adjuvants, Anesthesia', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Central Nervous System Depression', 'Decreased Central Nervous System Organized Electrical Activity', 'Fatty Acids', 'Fatty Acids, Volatile', 'Hydroxy Acids', 'Hydroxybutyrates', 'Lipids']" +DB00937,Diethylpropion,Diethylpropionis an appetite suppressant used for the short term treatment of exogenous obesity in addition to calorie restriction.,"['P23975', 'Q01959']","Diethylpropion is a sympathomimetic stimulant drug marketed as an appetite suppressant. Chemically, it is the N,N-diethyl analog of cathinone. Its mechanism of action is similar to other appetite suppressants such as sibutramine, phentermine and dextroamphetamine.",CCN(CC)C(C)C(=O)C1=CC=CC=C1,"Diethylpropion is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. Diethylpropion (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that diethylpropion can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent dopamine transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Amines', 'Amphetamines', 'Anti-Obesity Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Appetite Depressants', 'Appetite Suppression', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Ethylamines', 'Increased Sympathetic Activity', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Stimulants', 'Sympathomimetic Amine Anorectic', 'Sympathomimetics']" +DB00574,Fenfluramine,"Fenfluramineis fenfluramine is a phenethylamine that is structurally similar to serotonin. Due to its ability to increase extracellular serotonin levels, modulate serotonergic and other neurologic receptors, and control neurotransmission, it is effective in treating pharmacoresistant seizures.","['P31645', 'P28221', 'P28335', 'Q99720', 'P28223', 'P41595', 'P08908']","Fenfluramine increases extracellular serotonin levels, and also acts as both a serotonergic 5-HT2receptor agonist and σ1 receptor antagonist. These activities, through an incompletely understood mechanism, lead to anti-epileptiform activity and therapeutic benefit.1,2,3,4,5,6,7,8,16This modulation has other effects such as decreased appetite, weight loss, sedation, lethargy, increased blood pressure, and mood alteration including possible suicidal ideation. There is a risk of glaucoma and potentially fatal serotonin syndrome. Fenfluramine should be gradually withdrawn following treatment alteration or cessation.16",CCNC(C)CC1=CC=CC(=C1)C(F)(F)F,"Dravet syndrome is a complex pediatric encephalopathy characterized by recurrent pharmacoresistant seizures of variable type, delayed development, and in many cases, impairment in speech, language, gait, and other neurocognitive functions.,,,Despite substantial variation in presentation and severity, roughly % of patients with Dravet syndrome have mutations in theSCNAgene, which encodes the alpha subunit of a voltage-gated sodium channel (Nav.).,,,,,This channel is predominantly localized in inhibitory GABAergic interneurons as well as in excitatory pyramidal neurons; it is thought that dysfunction of neurotransmission regulation results in the seizures and other corresponding symptoms of Dravet syndrome.,Variousin vitroandin vivostudies have demonstrated that fenfluramine is capable of acting as an agonist of multiple serotonin receptors including -HTA, -HTD, -HTA, -HTB, and -HTC, as well as a σ receptor antagonist.,,,,,,,,This is at least partly because fenfluramine, as well as its active metabolite norfenfluramine, can act on sodium-dependent serotonin transporters (SERTs) to reverse transport direction and thereby increase extracellular serotonin levels.,However, work in animal models of Dravet syndrome suggest that only the modulation of -HTD, -HTC, σ, and possibly -HTAreceptors of fenfluramine result in the anti-epileptiform activity.,,Interestingly, -HTBreceptor agonism, which had previously been associated with cardiac valvulopathy,,is not anticipated to have any therapeutic value in Dravet syndrome.Although the exact mechanism by which stimulation/inhibition of various receptors leads to the observed therapeutic benefit is unclear, it is hypothesized to be two-fold. Stimulation of -HTDand -HTCmay result in increased GABAergic neurotransmission, while σ receptor antagonism may help to modulate responses toN-methyl-D-aspartate (NMDA).TargetActionsOrganismASodium-dependent serotonin transportersubstrateinhibitorHumansA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor CagonistHumansASigma non-opioid intracellular receptor antagonistHumansU-hydroxytryptamine receptor AagonistHumansN-hydroxytryptamine receptor BagonistHumansN-hydroxytryptamine receptor AagonistHumans",[],"['Alimentary Tract and Metabolism', 'Amines', 'Anticonvulsants', 'Antidepressive Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ethylamines', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Phenethylamines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Stimulants']" +DB01586,Ursodeoxycholic acid,Ursodeoxycholic acidis a bile acid used for the treatment of primary biliary cirrhosis (PBC).,"['P52895', 'Q96RI1']","Ursodeoxycholic acid (UDCA) is a secondary bile acid with cytoprotectant, immunomodulating, and choleretic effects. It reduces the cholesterol fraction of biliary lipids.1UDCA inhibits the absorption of cholesterol in the intestine and the secretion of cholesterol into bile, decreasing biliary cholesterol saturation.1UDCA increases bile acid flow and promotes the secretion of bile acids.1,3,6",[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O,"Endogenous hydrophobic bile acids such as deoxycholic acid and chenodeoxycholic acid can exert hepatotoxic effects. Ursodeoxycholic acid is a hydrophilic bile acid that mediates its biological effects via several mechanisms. Ursodeoxycholic acid (UDCA) protects hepatocytes and cholangiocytes from bile acid-induced damage, such as reactive oxygen species (ROS)-induced inflammation and mitochondrial dysfunction.UDCA was shown to reserve hepatocyte cell structures and stimulate anti-apoptotic pathways.,,,It was also shown to prevent the production of ROS by Kupffer cells and resident macrophages in the liver, thus attenuating oxidative stress in the liver.UDCA can also change the hydrophobicity index of the bile acid pool: following oral administration, UDCA forms a major fraction of the human bile acid pool and competitively displaces the hydrophobic or more toxic bile acids.,It increases the absorption of hydrophilic bile acids.There are several proposed mechanisms of choleretic actions of UDCA: UDCA increases intracellular calcium levels, stimulating transport proteins and vesicular exocytosis in cholestatic hepatocytes.UDCA may also upregulate the expression of membrane transport proteins like the chloride-bicarbonate anion exchanger (AE),,which is involved in biliary secretion and is often observed to be defective in primary biliary cholangitis.In rats, UDCA reduced hepatic expression of major histocompatibility complex (MHC) class I antigens, suggesting immunomodulating effects.UDCA acts as a partial agonist at the bile acid receptor, also known as the farnesoid X receptor (FXR), and has negligible effects on cholesterol and lipid synthesis.TargetActionsOrganismAAldo-keto reductase family member CinhibitorHumansUBile acid receptorpartial agonistHumans",[],"['Alimentary Tract and Metabolism', 'Bile Acid Preparations', 'Bile acids and derivatives', 'Bile Acids and Salts', 'Bile and Liver Therapy', 'Bile Therapy', 'BSEP/ABCB11 inducers', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cholagogues and Choleretics', 'Cholanes', 'Cholelitholytic Agents', 'Cholic Acids', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 Enzyme Inducers', 'Fused-Ring Compounds', 'Gastrointestinal Agents', 'Steroids']" +DB00851,Dacarbazine,Dacarbazineis an antineoplastic agent used to treat malignant melanoma and Hodgkin's disease.,"['Q14181', 'P52209']","Dacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.",CN(C)\N=N\C1=C(N=CN1)C(N)=O,"The mechanism of action is not known, but appears to exert cytotoxic effects via its action as an alkylating agent. Other theories include DNA synthesis inhibition by its action as a purine analog, and interaction with SH groups. Dacarbazine is not cell cycle-phase specific.TargetActionsOrganismADNAcross-linking/alkylationHumansUDNA polymerase alpha subunit Bother/unknownHumansU-phosphogluconate dehydrogenase, decarboxylatinginhibitorHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Imidazoles', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Toxic Actions', 'Triazenes']" +DB09130,Copper,"Copperis a transition metal found in a variety of supplements and vitamins, including intravenous solutions for total parenteral nutrition (TPN).","['P05067', 'P23526', 'P62807', 'P04406', 'P15531', 'P10412', 'Q06830', 'P05109', 'P08865', 'P63261', 'P06733', 'P68104', 'P05787', 'P07237', 'P30101', 'P10809', 'P48723', 'P11021', 'P14625', 'P02787', 'Q08288', 'P15880', 'Q07955', 'P22626', 'P31943', 'P31942', 'P61987', 'P14866', 'P23246', 'Q15428', 'P63244', 'P12814', 'Q03154', 'P09525', 'P08758', 'P27797', 'P14618', 'P14550', 'P00387', 'P00390', 'P29401', 'P32119', 'P30041', 'P62937', 'P11142', 'P07900', 'Q15185', 'P31948', 'Q96RE1', 'P56537', 'P60842', 'P06744', 'P00338', 'P00558', 'Q13748', 'P07437', 'P23528', 'P31946', 'P17174', 'P48637', 'P51858', 'P50213', 'O00299', 'Q06323', 'P30086', 'P18669', 'P43487', 'O60701', 'P61769', 'O75880', 'F7VJQ1', 'P23415', 'P42858', 'Q96FI4', 'Q969S2', 'Q6MZM0', 'P05121', 'P29034', 'P26447', 'P37840', 'P23560', 'Q99497', 'P10997', 'Q9UHF0', 'P04217', 'P43652', 'P01019', 'P02765', 'P02743', 'P02647', 'P02652', 'P06727', 'Q0VD83', 'P02655', 'P02656', 'P05090', 'P02649', 'P02749', 'P25311', 'P02747', 'P09871', 'P01024', 'P0C0L5', 'P04003', 'P01031', 'P07358', 'P02748', 'P08603', 'P05156', 'P05452', 'P10909', 'P00734', 'Q07021', 'P06396', 'P69905', 'P68871', 'P45973', 'P00739', 'P35858', 'P01857', 'P01861', 'P01619', 'P15814', 'P19823', 'P01042', 'P04264', 'P13645', 'P35908', 'P35527', 'P02750', 'P51884', 'Q96PD5', 'P00747', 'P27169', 'P02775', 'P01009', 'P29622', 'P08185', 'P05543', 'P01008', 'P05546', 'P36955', 'P08697', 'P05155', 'P02766', 'P04004', 'P51693']",Copper is incorporated into many enzymes throughout the body as an essential part of their function2. Copper ions are known to reduce fertility when released from copper-containing IUDs3.,[Cu],"Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-. It is believed that copper is reduced to the Cu+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX which shuttles the ion to copper transporting ATPase- on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (-%), albumin (%), and alpha -macroglobulin (%).Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor. It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine--oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor.Copper appears to reduce the viabilty and motility of spermatozoa. This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect. The exact mechanism of copper's effect on sperm are unknown.TargetActionsOrganismUAmyloid beta A proteinbinderHumansUAdenosylhomocysteinaseallosteric modulatorHumansUHistone HB type -C/E/F/G/INot AvailableHumansUGlyceraldehyde--phosphate dehydrogenaseNot AvailableHumansUNucleoside diphosphate kinase ANot AvailableHumansUHistone H.Not AvailableHumansUPeroxiredoxin-Not AvailableHumansUProtein S-ANot AvailableHumansUS ribosomal protein SANot AvailableHumansUActin, cytoplasmic Not AvailableHumansUAlpha-enolaseNot AvailableHumansUElongation factor -alpha Not AvailableHumansUKeratin, type II cytoskeletal Not AvailableHumansUProtein disulfide-isomeraseNot AvailableHumansUProtein disulfide-isomerase ANot AvailableHumansU kDa heat shock protein, mitochondrialNot AvailableHumansUHeat shock kDa protein Not AvailableHumansU kDa glucose-regulated proteinNot AvailableHumansUEndoplasminNot AvailableHumansUSerotransferrinNot AvailableHumansUCell growth-regulating nucleolar proteinNot AvailableMouseUS ribosomal protein SNot AvailableHumansUSerine/arginine-rich splicing factor Not AvailableHumansUHeterogeneous nuclear ribonucleoproteins A/BNot AvailableHumansUHeterogeneous nuclear ribonucleoprotein HNot AvailableHumansUHeterogeneous nuclear ribonucleoprotein HNot AvailableHumansUCobalt-precorrin-B C()-methyltransferaseNot AvailableTreponema denticola (strain ATCC / CIP / DSM )UHeterogeneous nuclear ribonucleoprotein LNot AvailableHumansUSplicing factor, proline- and glutamine-richNot AvailableHumansUSplicing factor A subunit Not AvailableHumansUReceptor of activated protein C kinase Not AvailableHumansUAlpha-actinin-Not AvailableHumansUAminoacylase-Not AvailableHumansUAnnexin ANot AvailableHumansUAnnexin ANot AvailableHumansUCalreticulinNot AvailableHumansUPyruvate kinase PKMNot AvailableHumansUAlcohol dehydrogenase [NADP(+)]Not AvailableHumansUNADH-cytochrome b reductase Not AvailableHumansUGlutathione reductase, mitochondrialNot AvailableHumansUTransketolaseNot AvailableHumansUPeroxiredoxin-Not AvailableHumansUPeroxiredoxin-Not AvailableHumansUPeptidyl-prolyl cis-trans isomerase ANot AvailableHumansUHeat shock cognate kDa proteinNot AvailableHumansUHeat shock protein HSP -alphaNot AvailableHumansUProstaglandin E synthase Not AvailableHumansUStress-induced-phosphoprotein Not AvailableHumansUTranslation elongation factor alpha -like Not AvailableHumansUEukaryotic translation initiation factor Not AvailableHumansUEukaryotic initiation factor A-INot AvailableHumansUGlucose--phosphate isomeraseNot AvailableHumansUL-lactate dehydrogenase A chainNot AvailableHumansUPhosphoglycerate kinase Not AvailableHumansUTubulin alpha C/D chainNot AvailableHumansUTubulin beta chainNot AvailableHumansUCofilin-Not AvailableHumansU-- protein beta/alphaNot AvailableHumansUAspartate aminotransferase, cytoplasmicNot AvailableHumansUGlutathione synthetaseNot AvailableHumansUHepatoma-derived growth factorNot AvailableHumansUIsocitrate dehydrogenase [NAD] subunit alpha, mitochondrialNot AvailableHumansUChloride intracellular channel protein Not AvailableHumansUProteasome activator complex subunit Not AvailableHumansUPhosphatidylethanolamine-binding protein Not AvailableHumansUPhosphoglycerate mutase Not AvailableHumansURan-specific GTPase-activating proteinNot AvailableHumansUUDP-glucose -dehydrogenaseNot AvailableHumansUBeta--microglobulinNot AvailableHumansUProtein SCO homolog, mitochondrialNot AvailableHumansUAlternative prion proteinNot AvailableHumansUGlycine receptor subunit alpha-Not AvailableHumansUHuntingtinNot AvailableHumansUEndonuclease -like Not AvailableHumansUEndonuclease -like Not AvailableHumansUHephaestin-like protein cofactorHumansUPlasminogen activator inhibitor Not AvailableHumansUProtein S-ANot AvailableHumansUProtein S-ANot AvailableHumansUAlpha-synucleinNot AvailableHumansUBrain-derived neurotrophic factorcofactorHumansUProtein DJ-Not AvailableHumansUIslet amyloid polypeptideNot AvailableHumansUTachykinin-Not AvailableHumansUAlpha-B-glycoproteinNot AvailableHumansUAfaminNot AvailableHumansUAngiotensinogenNot AvailableHumansUAlpha--HS-glycoproteinNot AvailableHumansUSerum amyloid P-componentNot AvailableHumansUApolipoprotein A-INot AvailableHumansUApolipoprotein A-IINot AvailableHumansUApolipoprotein A-IVNot AvailableHumansUApolipoprotein B receptorNot AvailableHumansUApolipoprotein C-IINot AvailableHumansUApolipoprotein C-IIINot AvailableHumansUApolipoprotein DNot AvailableHumansUApolipoprotein ENot AvailableHumansUBeta--glycoprotein Not AvailableHumansUZinc-alpha--glycoproteinNot AvailableHumansUComplement Cq subcomponent subunit CNot AvailableHumansUComplement Cs subcomponentNot AvailableHumansUComplement CNot AvailableHumansUComplement C-BNot AvailableHumansUCb-binding protein alpha chainNot AvailableHumansUComplement CNot AvailableHumansUComplement component C beta chainNot AvailableHumansUComplement component CNot AvailableHumansUComplement factor HNot AvailableHumansUComplement factor INot AvailableHumansUTetranectinNot AvailableHumansUClusterinNot AvailableHumansUProthrombinNot AvailableHumansUComplement component Q subcomponent-binding protein, mitochondrialNot AvailableHumansUGelsolinNot AvailableHumansUHemoglobin subunit alphaNot AvailableHumansUHemoglobin subunit betaNot AvailableHumansUChromobox protein homolog Not AvailableHumansUHaptoglobin-related proteinNot AvailableHumansUInsulin-like growth factor-binding protein complex acid labile subunitNot AvailableHumansUIg gamma- chain C regionNot AvailableHumansUIg gamma- chain C regionNot AvailableHumansUIg kappa chain V-III region GOLNot AvailableHumansUImmunoglobulin lambda-like polypeptide Not AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUKininogen-Not AvailableHumansUKeratin, type II cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type II cytoskeletal epidermalNot AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansULeucine-rich alpha--glycoproteinNot AvailableHumansULumicanNot AvailableHumansUN-acetylmuramoyl-L-alanine amidaseNot AvailableHumansUPlasminogenNot AvailableHumansUSerum paraoxonase/arylesterase Not AvailableHumansUPlatelet basic proteinNot AvailableHumansUAlpha--antitrypsinNot AvailableHumansUKallistatinNot AvailableHumansUCorticosteroid-binding globulinNot AvailableHumansUThyroxine-binding globulinNot AvailableHumansUAntithrombin-IIINot AvailableHumansUHeparin cofactor Not AvailableHumansUPigment epithelium-derived factorNot AvailableHumansUAlpha--antiplasminNot AvailableHumansUPlasma protease C inhibitorNot AvailableHumansUTransthyretinNot AvailableHumansUVitronectinNot AvailableHumansUAmyloid-like protein cofactorHumans","['Emergency Contraception', 'IUD therapy', 'Trace Element Deficiency', 'Dietary supplementation']","['Copper-containing Intrauterine Device', 'Decreased Embryonic Implantation', 'Decreased Sperm Motility', 'Diet, Food, and Nutrition', 'Elements', 'Food', 'Inhibit Ovum Fertilization', 'Metals', 'Metals, Heavy', 'Micronutrients', 'Minerals', 'Physiological Phenomena', 'Replacement Preparations', 'Trace Elements', 'Transition Elements']" +DB01592,Iron,Ironis an essential element commonly used for the treatment of patients with documented iron deficiency.,"['P02786', 'Q9GZT9', 'Q9BY41', 'Q9NZD4', 'P69905', 'Q16595', 'P02794', 'P39748', 'Q96FI4', 'Q969S2', 'P06746', 'P00450', 'P02787']","The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities.",[Fe],"Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.TargetActionsOrganismUTransferrin receptor protein Not AvailableHumansUEgl nine homolog Not AvailableHumansUHistone deacetylase cofactorHumansUAlpha-hemoglobin-stabilizing proteinNot AvailableHumansUHemoglobin subunit alphaNot AvailableHumansUFrataxin, mitochondrialNot AvailableHumansUFerritin heavy chainNot AvailableHumansUFlap endonuclease Not AvailableHumansUEndonuclease -like Not AvailableHumansUEndonuclease -like Not AvailableHumansUDNA polymerase betaNot AvailableHumansUCeruloplasminNot AvailableHumansUSerotransferrinNot AvailableHumans","['Nutritional supplementation', 'Dietary supplementation']","['Alimentary Tract and Metabolism', 'Antianemia Drugs', 'Antianemic Preparations', 'Blood and Blood Forming Organs', 'Diet, Food, and Nutrition', 'Elements', 'Food', 'Iron Compounds', 'Iron Preparations', 'Metals', 'Metals, Heavy', 'Micronutrients', 'Minerals', 'Physiological Phenomena', 'Supplements', 'Trace Elements', 'Transition Elements']" +DB00358,Mefloquine,Mefloquineis an antimalarial agent used in the prophylaxis and treatment of malaria caused by Plasmodium falciparum and Plasmodium vivax.,['P29274'],"Sporozoites located in the salivary glands of mosquitoes infected with malaria parasites are introduced into the bloodstream of a human host during mosquito feeding. These sporozoites rapidly invade the liver, where they mature into liver-stage schizonts, rupturing and releasing 2,000 - 40,000 merozoites that invade red blood cells.19Mefloquine is an antimalarial drug acting as a blood schizonticide, preventing and treating malaria.1,3",OC(C1CCCCN1)C1=CC(=NC2=C1C=CC=C2C(F)(F)F)C(F)(F)F,"The mechanism of action of mefloquine is not completely understood. Some studies suggest that mefloquine specifically targets the S ribosome of the Plasmodium falciparum, inhibiting protein synthesis and causing subsequent schizonticidal effects.There are other studies in the literature with limited in vitro data on mefloquine's mechanism of action.,TargetActionsOrganismAFe(II)-protoporphyrin IXbinderPlasmodium falciparumAS ribosomal subunitbinderPlasmodium falciparumUAdenosine receptor AaantagonistHumans",[],"['Agents Causing Muscle Toxicity', 'Agents that reduce seizure threshold', 'Aminoquinolines', 'Anti-Infective Agents', 'Antimalarial methanolquinolines', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines']" +DB00282,Pamidronic acid,"Pamidronic acidis a bisphosphonate used to treat Paget's disease, to treat hypercalcemia of malignancy, and to treat osteolytic bone lesions.","['P14324', 'O95749', 'P42574', 'P55211']","Pamidronic acid is a second generation, nitrogen containing bisphosphonate that inhibits osteoclast mediated bone loss2,3,11It has a wide therapeutic index and a long duration of action as it can be given every 3-4 weeks for certain indications.11Patients should be counselled regarding the risk of elevated blood urea nitrogen, renal tubular necrosis, and nephrotoxicity.11",NCCC(O)(P(O)(O)=O)P(O)(O)=O,"Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis.Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.Osteoclasts mediate resorption of bone.When osteoclasts bind to bone they form podosomes, ring structures of F-actin.Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.Nitrogen containing bisphosphonates such as pamidronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate.,,These components are essential for post-translational prenylation of GTP-binding proteins like Rap.,The lack of prenylation of these proteins interferes with their function, and in the case of Rap, leads to apoptosis.,pamidronate also activated caspases and which further contribute to apoptosis.,,TargetActionsOrganismAFarnesyl pyrophosphate synthaseinhibitorHumansAHydroxylapatiteantagonistHumansUGeranylgeranyl pyrophosphate synthaseinhibitorHumansUCaspase-activatorHumansUCaspase-activatorHumans",[],"['Agents Causing Muscle Toxicity', 'Antineoplastic Agents', 'Bisphosphonates', 'Bone Density Conservation Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Organophosphonates', 'Organophosphorus Compounds']" +DB01026,Ketoconazole,Ketoconazoleis a broad spectrum antifungal used to treat seborrheic dermatitis and fungal skin infections.,"['P50859', 'P05093', 'P10275', 'P08686', 'Q12809', 'O75469', 'Q14994']","Ketoconazole, similarly to other azole antifungals, is a fungistatic agent which causes growth arrest in fungal cells thereby preventing growth and spread of the fungus throughout the body.11",CC(=O)N1CCN(CC1)C1=CC=C(OCC2COC(CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1,"Ketoconazole interacts with -α-sterol demethylase, a cytochrome P- enzyme necessary for the conversion of lanosterol to ergosterol.,This results in inhibition of ergosterol synthesis and increased fungal cellular permeability due to reduced amounts of ergosterol present in the fungal cell membrane. This metabolic inhibition also results in accumulation of α-methyl-,-diol, a toxic metabolite. The increase in membrane fluidity is also thought to produce impairment of membrane-bound enzyme systems as components become less closely packed.TargetActionsOrganismALanosterol -alpha demethylaseinhibitorASteroid -alpha-hydroxylase/, lyaseinhibitorHumansUAndrogen receptorbinderHumansUSteroid -hydroxylaseinhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUNuclear receptor subfamily group I member antagonistHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['14-alpha Demethylase Inhibitors', 'Agents causing hyperkalemia', 'Anti-Infective Agents', 'Antiadrenal Preparations', 'Anticorticosteroids', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Azole Antifungals', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Gynecological Antiinfectives and Antiseptics', 'Hepatotoxic Agents', 'Imidazole and Triazole Derivatives', 'Imidazole Derivatives', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Piperazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Steroid Synthesis Inhibitors', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'UGT1A1 Inhibitors', 'UGT2B7 Inhibitors']" +DB01115,Nifedipine,"Nifedipineis a dihydropyridine calcium channel blocker indicated for the management of several subtypes of angina pectoris, and hypertension.","['Q13936', 'Q01668', 'Q08289', 'O75469', 'P0DP23', 'Q13698', 'Q9UK17', 'O43497', 'O95180', 'Q9P0X4']","Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart.1Immediate release nifedipine's duration of action requires dosing 3 times daily.13Nifedipine dosing is generally 10-120mg daily.13Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.13",COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OC,"Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells.This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries.These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansUNuclear receptor subfamily group I member agonistHumansUCalmodulininhibitorHumansUVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansUPotassium voltage-gated channel subfamily D member inhibitorHumansUVoltage-dependent T-type calcium channelinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Beta blocking agents and calcium channel blockers', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium Channel Blockers and Diuretics', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Negative Inotrope', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Pyridines', 'QTc Prolonging Agents', 'Reproductive Control Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Tocolytic Agents', 'Vasodilating Agents']" +DB00661,Verapamil,"Verapamilis a non-dihydropyridine calcium channel blocker used in the treatment of angina, arrhythmia, and hypertension.","['Q13936', 'Q00975', 'O00555', 'Q14654', 'O43497', 'O95180', 'Q12809', 'P31645', 'P35348', 'P35368', 'P25100', 'Q06432', 'Q9Y698', 'O60359', 'Q9UBN1', 'Q9UF02', 'Q9BXT2', 'P62955', 'Q8WXS5', 'P54289', 'Q9NY47', 'Q8IZS8', 'Q7Z3S7', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'Q00975', 'O00555', 'Q15878', 'O43497', 'O95180', 'Q9P0X4', 'P08183']","Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity.19Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times daily,19but extended-release formulations are available that allow for once-daily dosing.17,22As verapamil is a negative inotropic medication (i.e. it decreases the strength of myocardial contraction), it should not be used in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy as the decrease in contractility caused by verapamil may increase the risk of exacerbating these pre-existing conditions.17",COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1,"Verapamil inhibits L-type calcium channels by binding to a specific area of their alpha- subunit,Cav., which is highly expressed on L-type calcium channels in vascular smooth muscle and myocardial tissue where these channels are responsible for the control of peripheral vascular resistance and heart contractility.Calcium influx through these channels allows for the propagation of action potentials necessary for the contraction of muscle tissue and the heart's electrical pacemaker activity. Verapamil binds to these channels in a voltage- and frequency-dependent manner, meaning affinity is increased ) as vascular smooth muscle membrane potential is reduced, and ) with excessive depolarizing stimulus.Verapamil's mechanism of action in the treatment of angina and hypertension is likely due to the mechanism described above. Inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation - this lowers systemic vascular resistance (i.e. afterload) and thus blood pressure. This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina.Electrical activity through the AV node is responsible for determining heart rate, and this activity is dependent upon calcium influx through L-type calcium channels. By inhibiting these channels and decreasing the influx of calcium, verapamil prolongs the refractory period of the AV node and slows conduction, thereby slowing and controlling the heart rate in patients with arrhythmia.Verapamil's mechanism of action in the treatment of cluster headaches is unclear, but is thought to result from an effect on other calcium channels (e.g. N-, P-, Q-, or T-type).Verapamil is known to interact with other targets, including other calcium channels,,,,potassium channels,,,and adrenergic receptors.,TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansUVoltage-dependent N-type calcium channel subunit alpha-BinhibitorHumansUVoltage-dependent P/Q-type calcium channel subunit alpha-AinhibitorHumansUATP-sensitive inward rectifier potassium channel inhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUSodium-dependent serotonin transporterunknownHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumansUVoltage-dependent calcium channelinhibitorHumansUP-glycoprotein inhibitorblockerHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Amines', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Nondihydropyridine)', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'MATE 1 Inhibitors', 'MATE 2 Inhibitors', 'MATE inhibitors', 'Membrane Transport Modulators', 'Miscellaneous Calcium-channel Blocking Agents', 'Negative Inotrope', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT1 substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phenylalkylamine Derivatives', 'Selective Calcium Channel Blockers With Direct Cardiac Effects', 'Vasodilating Agents', 'Verapamil and analogues']" +DB00818,Propofol,Propofolis a medication used in general anesthesia and for sedation.,"['P47870', 'P28472', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P35499', 'Q99250']","Propofol is a sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of propofol produces hypnosis rapidly with minimal excitation, usually within 40 seconds from the start of an injection (the time for one arm-brain circulation).",CC(C)C1=CC=CC(C(C)C)=C1O,The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit beta-potentiatorHumansAGamma-aminobutyric acid receptor subunit beta-potentiatorHumansAGABA(A) Receptorpositive allosteric modulatorHumansUSodium channel protein type subunit alphainhibitorHumansUSodium channel protein type subunit alphainhibitorHumans,"['Induction of anesthesia therapy', 'Maintenance of anesthesia therapy', 'Monitored anesthesia care sedation', 'Sedative therapy']","['Agents Causing Muscle Toxicity', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Benzene Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hypnotics and Sedatives', 'Hypotensive Agents', 'Miscellaneous General Anesthetics', 'Nervous System', 'P-glycoprotein inducers', 'Phenols', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'UGT1A1 Inhibitors', 'UGT1A1 Substrates', 'UGT1A6 substrate', 'UGT1A9 Substrates']" +DB00252,Phenytoin,Phenytoinis an anticonvulsant drug used in the prophylaxis and control of various types of seizures.,"['Q14524', 'P35498', 'Q12809', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555', 'Q99250', 'Q9UQD0', 'O75469', 'Q07699', 'Q9NY46', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","Phenytoin is an anticonvulsant with a narrow therapeutic index.5Although the recommended therapeutic range is cited to be between 10-20 mg/L, differences in albumin levels, genetics, comorbidities, and body composition can make achieving an ideal phenytoin dose challenging.5For example, studies have confirmed that phenytoin metabolism is impacted by CYP2C9 genotype polymorphisms and possibly by CYP2C19 genotype polymorphisms (the latter has not been as extensively studied).5It is worth nothing that although phenytoin is highly protein bound, only the fraction unbound is able to exert a pharmacological effect.17Therefore, factors that reduce or increase the percentage of protein bound phenytoin (for example: concomitant administration of drugs that can cause displacement from protein binding sites) can have a marked impact on phenytoin therapy.4,17",O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1,"Although phenytoin first appeared in the literature in , it has taken decades for the mechanism of action to be more specifically elucidated.Although several scientists were convinced that phenytoin altered sodium permeability, it wasn’t until the ’s that this phenomenon was linked to voltage-gated sodium channels.Phenytoin is often described as a non-specific sodium channel blocker and targets almost all voltage-gated sodium channel subtypes.More specifically, phenytoin prevents seizures by inhibiting the positive feedback loop that results in neuronal propagation of high frequency action potentials.,,TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansAPotassium voltage-gated channel subfamily H member inhibitorHumansAVoltage-dependent L-type calcium channelinhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansUNuclear receptor subfamily group I member Not AvailableHumansUSodium channel subunit beta-Not AvailableHumansUSodium channel protein type subunit alphaNot AvailableHumansUGABA(A) ReceptorNot AvailableHumans",[],"['Agents Causing Muscle Toxicity', 'Anti-epileptic Agent', 'Anticonvulsants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'COMT Substrates', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers (strong)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (moderate)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strong)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (weak)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Enzyme Inducing Antiepileptic Drugs', 'Hydantoins', 'Hyperglycemia-Associated Agents', 'Imidazoles', 'Imidazolidines', 'Inducers of Drug Clearance', 'Membrane Transport Modulators', 'Methemoglobinemia Associated Agents', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Phenytoin and Prodrugs', 'Sodium Channel Blockers', 'Thyroxine-binding globulin substrates', 'UGT1A1 Inducers', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index', 'UGT1A4 substrates', 'UGT1A6 Inhibitors', 'UGT1A6 substrate', 'UGT1A6 Substrates with a Narrow Therapeutic Index', 'UGT1A9 Inhibitors', 'UGT1A9 Substrates', 'UGT1A9 Substrates with a Narrow Therapeutic Index', 'Voltage-Gated Sodium Channel Blockers']" +DB00500,Tolmetin,"Tolmetinis an NSAID used to treat acute flares of various painful conditions and used for the long term management of osteoarthritis, rheumatoid arthritis, and juvenile arthritis.","['P35354', 'P23219']","Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions. tolmetin has produced additional therapeutic benefit when added to a regimen of gold salts and, to a lesser extent, with corticosteroids. Tolmetin should not be used in conjunction with salicylates since greater benefit from the combination is not likely, but the potential for adverse reactions is increased.",CN1C(CC(O)=O)=CC=C1C(=O)C1=CC=C(C)C=C1,"The mode of action of tolmetin is not known. However, studies in laboratory animals and man have demonstrated that the anti-inflammatory action of tolmetin is not due to pituitary-adrenal stimulation. Tolmetin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in man. This reduction in prostaglandin synthesis may be responsible for the anti-inflammatory action. Tolmetin does not appear to alter the course of the underlying disease in man.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain']" +DB00788,Naproxen,"Naproxenis an NSAID used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, tendinitis, bursitis, acute gout, primary dysmenorrhea, and mild to moderate pain.","['P23219', 'P35354', 'Q51911']","Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic.5Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood.5Although naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control.10A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use.10Further, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs.11Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers.11",COC1=CC2=C(C=C1)C=C(C=C2)[C@H](C)C(O)=O,"As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX- and COX- enzymes leading to decreased prostaglandin synthesis.Although both enzymes contribute to prostaglandin production, they have unique functional differences.The COX- enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX- enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation.The COX- enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX- enzyme.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansUPeptostreptococcal albumin-binding proteinNot AvailablePeptostreptococcus magnus",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antigout Preparations', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antiinflammatory Products for Vaginal Administration', 'Antirheumatic Agents', 'BSEP/ABCB11 Substrates', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Musculo-Skeletal System', 'Naphthaleneacetic Acids', 'Naphthalenes', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Propionates', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A6 substrate', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB08889,Carfilzomib,Carfilzomibis a proteasome inhibitor used either alone or in conjunction with a chemotherapy regimen to treat patients with relapsed or refractory multiple myeloma.,"['P28074', 'P28062', 'P20618', 'P28065', 'P49721', 'P40306']","Intravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib.",CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1,"Carfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the S proteasome, the proteolytic core particle within the S proteasome. This S core has catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (β and βi subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites.TargetActionsOrganismAProteasome subunit beta type-inhibitorHumansAProteasome subunit beta type-inhibitorHumansAProteasome subunit beta type-inhibitorHumansAProteasome subunit beta type-inhibitorHumansAProteasome subunit beta type-inhibitorHumansAProteasome subunit beta type-inhibitorHumans",[],"['Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Peptides', 'Proteasome Inhibitors']" +DB00388,Phenylephrine,"Phenylephrineis an alpha-1 adrenergic agonist used in the management of hypotension, generally in the surgical setting associated with the use of anesthetics.","['P35348', 'P35368', 'P25100']","Phenylephrine is an alpha-1 adrenergic agonist that raises blood pressure,6,8dilates the pupils,7and causes local vasoconstriction.1Ophthalmic formulations of phenylephrine act for 3-8 hours7while intravenous solutions have an effective half life of 5 minutes and an elimination half life of 2.5 hours.3,6Patients taking ophthalmic formulations of phenylephrine should be counselled about the risk of arrhythmia, hypertension, and rebound miosis.7Patients taking an intravenous formulation should be counselled regarding the risk of bradycardia, allergic reactions, extravasation causing necrosis or tissue sloughing, and the concomitant use of oxytocic drugs.6,8",CNC[C@H](O)C1=CC(O)=CC=C1,"Phenylephrine is an alpha- adrenergic agonist that mediates vasoconstrictionand mydriasisdepending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha- adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance.,Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia.,TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-D adrenergic receptoragonistHumans","['Airway secretion clearance therapy', 'Mydriasis', 'Antihistamine', 'Vasoconstrictor in regional analgesia therapy']","['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Autonomic Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Decongestants and Antiallergics', 'Ethanolamines', 'Monoamine Oxidase A Substrates', 'Mydriatics', 'Mydriatics and Cycloplegics', 'Nasal Decongestants', 'Nasal Decongestants for Systemic Use', 'Nasal Preparations', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Protective Agents', 'Respiratory System Agents', 'Sensory Organs', 'Sympathomimetic (Adrenergic) Agents', 'Sympathomimetics', 'Sympathomimetics Excl. Antiglaucoma Preparations', 'Sympathomimetics Used as Decongestants', 'Sympathomimetics, Plain', 'Vasoconstrictor Agents']" +DB00489,Sotalol,Sotalolis a methane sulfonanilide beta adrenergic antagonist used to treat life-threatening ventricular arrhythmias and to maintain sinus rhythm in atrial fibrillation or flutter.,"['P08588', 'P07550', 'Q12809']","Sotalol is a competitive inhibitor of the rapid potassium channel.2This inhibition lengthens the duration of action potentials and the refractory period in the atria and ventricles.3,4The inhibition of rapid potassium channels is increases as heart rate decreases, which is why adverse effects like torsades de points is more likely to be seen at lower heart rates.6L-sotalol also has beta adrenergic receptor blocking activity seen above plasma concentrations of 800ng/L.6The beta blocking ability of sotalol further prolongs action potentials.6D-sotalol does not have beta blocking activity but also reduces a patient's heart rate while standing or exercising.6These actions combine to produce a negative inotropic effect that reduces the strength of contractility of muscle cells in the heart.2Extension of the QT interval is also adversely associated with the induction of arrhythmia in patients.4Hyperglycemia is a greater risk for non insulin dependant diabetics than insulin dependant diabetics.7Beta blockers inhibit insulin secretion which may cause hyperglycemia in type II diabetes mellitus.7The risk of hypoglycemia is higher in insulin dependant diabetes than non insulin dependant diabetics.7Beta blockers decrease secretion of insulin, which may mask hypoglycemia in an insulin dependant patient.7Beta blockers also increase glucose uptake into cells which may prolong or potentiate hypoglycemia.7Further information regarding adverse reactions can be found here.11",CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1,"Sotalol inhibits beta- adrenoceptors in the myocardium as well as rapid potassium channels to slow repolarization, lengthen the QT interval, and slow and shorten conduction of action potentials through the atria.,,,The action of sotalol on beta adrenergic receptors lengthens the sinus node cycle, conduction time through the atrioventricular node, refractory period, and duration of action potentials.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumansAPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Autonomic Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Non-Selective', 'Beta Blocking Agents, Non-Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cardiac Rhythm Alteration', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Ethanolamines', 'Highest Risk QTc-Prolonging Agents', 'Hypotensive Agents', 'Narrow Therapeutic Index Drugs', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'QTc Prolonging Agents', 'Sympatholytics']" +DB01393,Bezafibrate,"Bezafibrateis a lipid-lowering fibrate used in the management of primary and secondary hyperlipidaemia, when there is a lack of clinical improvement following lifestyle modifications or correction of the underlying disorder.","['Q03181', 'P37231', 'Q07869', 'O75469', 'P19793', 'P28702', 'P48443']","Bezafibrate is an antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol). Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoproteinlipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL) precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor-mediated lipoprotein catabolism. Elevated fibrinogen appears to be an important risk-factor, alongside the lipids, smoking and hypertension, in the development of atheroma. Fibrinogen plays an important role in viscosity, and therefore blood flow, and also appears to play an important role in thrombus development and lysability. Bezafibrate exerts an effect on thrombogenic factors. A significant decrease in elevated plasma fibrinogen levels can be achieved. This may lead, amongst other things, to a reduction in both blood and plasma viscosity. Inhibition of platelet aggregation has also been observed. A reduction in blood glucose concentration due to an increase in glucose tolerance has been reported in diabetic patients. In the same patients, the concentration of fasting and postprandial free fatty acids was reduced by bezafibrate.",CC(C)(OC1=CC=C(CCNC(=O)C2=CC=C(Cl)C=C2)C=C1)C(O)=O,"It is generally accepted that bezafibrate is likely an agonist of PPAR-alpha. However, certain other investigations have also suggested that the substance might also elicit some effects on PPAR-gamma and PPAR-delta too.TargetActionsOrganismAPeroxisome proliferator-activated receptor deltaagonistHumansAPeroxisome proliferator-activated receptor gammaagonistHumansAPeroxisome proliferator-activated receptor alphaagonistHumansUNuclear receptor subfamily group I member partial agonistHumansURetinoic acid receptor RXR-alphaagonistHumansURetinoic acid receptor RXR-betaagonistHumansURetinoic acid receptor RXR-gammaagonistHumans",[],"['Acids, Acyclic', 'Acids, Carbocyclic', 'Agents Causing Muscle Toxicity', 'Amides', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Butyrates', 'Chlorobenzoates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ethers', 'Fibric Acid Derivatives', 'Fibric Acids', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Isobutyrates', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia', 'OATP1B1/SLCO1B1 Inhibitors', 'Phenols', 'Phenyl Ethers']" +DB00178,Ramipril,Ramiprilis an ACE inhibitor used for the management of hypertension and the reduction of cardiovascular mortality following myocardial infarction in hemodynamically stable patients with clinical signs of congestive heart failure.,"['P12821', 'P46663']","Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril.5It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure.",[H][C@@]12CCC[C@]1([H])N([C@@H](C2)C(O)=O)C(=O)[C@H](C)N[C@@H](CCC1=CC=CC=C1)C(=O)OCC,"Ramipril inhibits the RAAS system by binding to and inhibiting ACE thereby preventing the conversion of angiotensin I to angiotensin II.As plasma levels of angiotensin II fall, less activation of the G-protein coupled receptors angiotensin receptor I (ATR) and angiotensin receptor II (ATR) occurs.ATR mediates vasoconstriction, inflammation, fibrosis, and oxidative stress through a variety of signaling pathways.These include Gqcoupling to the inositol triphosphate pathway, activation of phospholipases C, A, and D which contribute to eicosanoid production, activation of Ca+-dependent and MAP kinases, Giand G/, and eventual activation of the Jak/STAT pathway leading to cell growth and production of extracellular matrix components. ATR activation also leads to increased activity of membrane-bound NADH/NADPH oxidase which contributes to production of reactive oxygen species. Decreased activation of this receptor mediates the renoprotective, antihypertensive, and cardioprotective effects of ramipril by reducing inflammation and vasoconstriction.ATR acts in opposition to the effects of ATR by activating phosphotyrosine phosphatases which inhibit MAP kinases, inhibiting Ca+channel opening, and stimulating cGMP and nitric oxide production leading to vasodilation.These counteracting effects are shared by the Mas receptor which is activated by Ang(-), a subtype of angiotensin produced by plasma esterases from AngI or by ACE from AngII produced through a secondary pathway by tonin and cathepsin G. Ang(-) also activates ATR although the bulk of its effect is mediated by MasR.ACE is also responsible for the breakdown of bradykinin.The resulting buildup of bradykinin due to ACE inhibition is thought to mediate the characteristic dry-cough as a side effect of ACE inhibitor medications.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumansUB bradykinin receptorNot AvailableHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Cholinesterase Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Lipid Modifying Agents', 'Photosensitizing Agents', 'Protease Inhibitors']" +DB00945,Aspirin,"Aspirinis a salicylate used to treat pain, fever, inflammation, migraines, and reducing the risk of major adverse cardiovascular events.","['P23219', 'P35354', 'Q04828', 'Q13131', 'P54646', 'Q9Y478', 'O43741', 'P54619', 'Q9UGJ0', 'Q9UGI9', 'P25101', 'P04637', 'P11021', 'P51812', 'P25963', 'P98066', 'P29466', 'P42574', 'O14920', 'P28482', 'Q8TD08', 'P27361', 'P31152', 'Q16659', 'Q13164', 'P24385', 'P01106', 'P12004', 'Q99519']","Effects on pain and feverAcetylsalicylic acid disrupts the production of prostaglandins throughout the body by targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)9,10,11. Prostaglandins are potent, irritating substances that have been shown to cause headaches and pain upon injection into humans. Prostaglandins increase the sensitivity of pain receptors and substances such as histamine and bradykinin. Through the disruption of the production and prevention of release of prostaglandins in inflammation, this drug may stop their action at pain receptors, preventing symptoms of pain. Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere with the production of brain prostaglandin E1. Prostaglandin E1 is known to be an extremely powerful fever-inducing agentLabel.Effects on platelet aggregationThe inhibition of platelet aggregation by ASA occurs because of its interference with thromboxane A2 in platelets, caused by COX-1 inhibition. Thromboxane A2 is an important lipid responsible for platelet aggregation, which can lead to clot formation and future risk of heart attack or strokeLabel.A note on cancer preventionASA has been studied in recent years to determine its effect on the prevention of various malignancies15. In general, acetylsalicylic acid is involved in the interference of various cancer signaling pathways, sometimes inducing or upregulating tumor suppressor genes15,17. Results of various studies suggest that there are beneficial effects of long-term ASA use in the prevention of several types of cancer, including stomach, colorectal, pancreatic, and liver cancers16. Research is ongoing.",CC(=O)OC1=CC=CC=C1C(O)=O,"Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX- and COX- enzymes,,. Inhibition of COX- results in the inhibition of platelet aggregation for about - days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of the cyclooxygenase- (COX-) enzyme, leading to irreversible inhibition. This prevents the production of pain-causing prostaglandins. This process also stops the conversion of arachidonic acid to thromboxane A (TXA), which is a potent inducer of platelet aggregationLabel. Platelet aggregation can result in clots and harmful venous and arterial thromboembolism, leading to conditions such as pulmonary embolism and stroke.It is important to note that there is % homology between the protein structures of COX- and COX-. ASA binds to serine residue on the active site of COX- in the same fashion as its binding to the serine residue located on the active site of COX-. The active site of COX- is, however, slightly larger than the active site of COX-, so that arachidonic acid (which later becomes prostaglandins) manages to bypass the aspirin molecule inactivating COX-,. ASA, therefore, exerts more action on the COX- receptor rather than on the COX- receptor. A higher dose of acetylsalicylic acid is required for COX- inhibition.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansUAldo-keto reductase family member CinhibitorHumansU'-AMP-activated protein kinaseactivatorHumansUEndothelin- receptorinhibitorHumansUCellular tumor antigen pinducerHumansU kDa glucose-regulated proteininhibitorbinderHumansURibosomal protein S kinase alpha-inhibitorHumansUNF-kappa-B inhibitor alphainhibitorHumansUTumor necrosis factor-inducible gene proteininhibitordownregulatorHumansUCaspase-inhibitordownregulatorHumansUCaspase-inhibitordownregulatorHumansUInhibitor of nuclear factor kappa-B kinase subunit betaNot AvailableHumansUExtracellular signal-regulated kinase (ERK)Not AvailableHumansUG/S-specific cyclin-DdownregulatorHumansUMyc proto-oncogene proteindownregulatorHumansUProliferating cell nuclear antigendownregulatorHumansUCyclin AdownregulatorUSialidase-inhibitorHumans","['Anti-platelet Therapy', 'Hemodialysis Treatment', 'Secondary Prevention']","['Acids, Carbocyclic', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiplatelet agents', 'Antipyretics', 'Benzene Derivatives', 'Blood and Blood Forming Organs', 'Cardiovascular Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Decreased Platelet Aggregation', 'Decreased Prostaglandin Production', 'Drugs that are Mainly Renally Excreted', 'Hematologic Agents', 'Hydroxybenzoates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Salicylates', 'Salicylic Acid and Derivatives', 'Sensory System Agents', 'Stomatological Preparations', 'UGT1A6 substrate']" +DB00487,Pefloxacin,Pefloxacinis an antibiotic used to treat a variety of bacterial infections.,"['P43702', 'P43700', 'P11388', 'Q06AK7']","Pefloxacin is a fluoroquinolone antibiotic. Flouroquinolones such as pefloxacin possess excellent activity against gram-negative aerobic bacteria such asE.coliandNeisseria gonorrhoeaas well as gram-positive bacteria includingS. pneumoniaeandStaphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.",CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCN(C)CC1,"The bactericidal action of pefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.TargetActionsOrganismADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumansUDNA topoisomerase inhibitorStaphylococcus aureus",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00215,Citalopram,Citalopramis a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression.,"['P31645', 'P35367']","Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It has been found to relieve or manage symptoms of depression, anxiety, eating disorders and obsessive-compulsive disorder among other mood disorders. The antidepressant, anti-anxiety, and other actions of citalopram are linked to its inhibition of CNS central uptake of serotonin.19Serotonergic abnormalities have been reported in patients with mood disorders. Behavioral and neuropsychological effects of serotonin include the regulation of mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, as examples. The onset of action for depression is approximately 1 to 4 weeks. The complete response may take 8-12 weeks after initiation of citalopram.16In vitrostudies demonstrate that citalopram is a strong and selective inhibitor of neuronal serotonin reuptake and has weak effects on norepinephrine and dopamine central reuptake. The chronic administration of citalopram has been shown to downregulate central norepinephrine receptors, similar to other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase.4",CN(C)CCCC1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1,"The mechanism of action of citalopram is unclear but is presumed to be related to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (-HT), potentially through the inhibition of the serotonin transporter (solute carrier family member ,SLCA).,Citalopram binds with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. Particularly, citalopram has no or very low affinity for -HTA, -HTA, dopamine Dand D, α-, α-, and β-adrenergic, histamine H, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansNHistamine H receptorbinderHumans",[],"['Amines', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Benzofurans', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Hypoglycemia-Associated Agents', 'Monoamine Oxidase A Substrates', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Nitriles', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Propylamines', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Vasodilating Agents']" +DB00699,Nicergoline,Nicergolineis an ergot derivative use for the treatment of symptoms associated with cerebrovascular abnormalities.,['P35348'],"Nicergoline is a potent vasodilator (improves brain blood flow). On the cerebral level it prompts a lowering of vascular resistance, an increase in arterial flow and stimulates the use of oxygen and glucose. Nicergoline also improves blood circulation in the lungs and limbs and has been shown to inhibit blood platelet aggregation.",[H][C@@]12CC3=CN(C)C4=CC=CC(=C34)[C@]1(C[C@@H](COC(=O)C1=CN=CC(Br)=C1)CN2C)OC,"Nicergoline acts by inhibiting the postsynaptic alpha()-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation. Therefore the mechanism of Nicergoline is to increase vascular circulation in the brain, thereby enhancing the transmission of nerve signals across the nerve fibres, which secrete acetylcholine as a neural transmitter.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumans",['Peripheral vasodilatation'],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Alkaloids', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Heterocyclic Compounds, Fused-Ring', 'Neurotransmitter Agents', 'Nootropic Agents', 'Peripheral Vasodilators', 'Vasodilating Agents']" +DB00320,Dihydroergotamine,Dihydroergotamineis an ergot alkaloid used in the acute treatment of migraine headache and cluster headache.,"['P28222', 'P28221', 'P30939', 'P08913', 'P08908', 'P28566', 'P28223', 'P41595', 'P28335', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P14416', 'P35462', 'P21917', 'Q13639', 'P13945']","DHE is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.8,9,10It is thought to exert its therapeutic effect through both neurological and vascular mechanisms.3Its serotonin agonist activity may contribute to decreasing glutamatergic activity of the trigeminal system and subsequent cortical depolarization which is thought to participate in the neurological pathophysiology of migraine.2The same serotonin agonist activity also contributes to vasoconstriction, producing both the characteristic side effect of chest tightness and potentially contributing to a therapeutic effect by counteracting the vasodilation due to calcitonin gene-related peptide (CGRP) release in migraine attacks.3",[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O,"DHE has several proposed mechanisms which may contribute to its therapeutic efficacy as an abortive therapy in migraines. Firstly, DHE's s agonist action on -hydroxytryptamine (HT) b receptors in the smooth muscle of the cranial vasculature may provide relief via vasoconstriction of the blood vessels which typically become dilated due to the release of CGRP during migraine attacks.,DHE's off-target action at alpha-adrenergic receptors may further contribute via this mechanism. The remaining mechanisms are thought to provide relief through the effects on the neurogenic causes of migraine symptoms. Agonist action by DHE on -HTband -HTdreceptors inhibits nociceptive signalling through the ventroposteromedial thalamus to the trigeminal sensory neurons. Further action on -HTband -HTdreceptors with the addition of agonist activity on -HTfin the trigeminal nucleus caudalis decreases afferent signalling to trigeminal sensory neurons which contributes to central sensitization. The success of experimental compounds selectively targetting the -HTfreceptor lends support to this mechanism. Lastly, action at -HTdreceptors on trigeminal nerve terminals inhibits the release of vasoactive neuropeptides thought to contribute to pain and inflammation during a migraine attack. DHE is known to have -fold less potency at the -HTbreceptor than its predecessor ergotamine which reduces the incidence of vascular side effects.Notably, DHE slowly diffuses from receptors resulting in unreliable prediction of effects from plasma concentration.TargetActionsOrganismA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor FagonistHumansUAlpha-A adrenergic receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor EagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor CagonistHumansUAlpha- adrenergic receptorsagonistHumansUAlpha- adrenergic receptorsagonistHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansU-hydroxytryptamine receptor agonistHumansUBeta- adrenergic receptoragonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Alkaloids', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Ergot Alkaloids and Derivatives', 'Ergot-derivative Dopamine Receptor Agonists', 'Ergotamine Derivative', 'Ergotamines', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Sympatholytic (Adrenergic Blocking) Agents', 'Vasoconstrictor Agents']" +DB00604,Cisapride,Cisaprideis a medication used to treat heartburn associated with GERD.,"['Q13639', 'P46098', 'P28223', 'Q12809']","Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4agonist; upon activation of the receptor signaling pathway, cisapride promotes the release of acetylcholine neurotransmitters in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity.",CO[C@H]1CN(CCCOC2=CC=C(F)C=C2)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)C=C1OC,"Cisapride acts through the stimulation of the serotonin -HTreceptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit.TargetActionsOrganismA-hydroxytryptamine receptor agonistHumansA-hydroxytryptamine receptor AagonistHumansA-hydroxytryptamine receptor AagonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Acids, Carbocyclic', 'Alimentary Tract and Metabolism', 'Amides', 'Aminobenzoates', 'Anti-Ulcer Agents', 'Antidepressive Agents', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Depressants', 'Chlorobenzoates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Functional Gastrointestinal Disorders', 'Gastrointestinal Agents', 'Highest Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'para-Aminobenzoates', 'Piperidines', 'Propulsives', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Receptor Agonists']" +DB00335,Atenolol,"Atenololis a synthetic beta-1 selective blocker used in the management of hypertension and chronic angina, and to reduce mortality in known or suspected myocardial infarction in hemodynamically stable patients.","['P08588', 'P07550']","Atenolol is a cardio-selective beta-blocker and as such exerts most of its effects on the heart.LabelIt acts as an antagonist to sympathetic innervation and prevents increases in heart rate, electrical conductivity, and contractility in the heart due to increased release of norepinephrine from the peripheral nervous system.Label,24,14Together the decreases in contractility and rate produce a reduction in cardiac output resulting in a compensatory increase in peripheral vascular resistance in the short-term. This response later declines to baseline with long-term use of atenolol. More importantly, this reduction in the work demanded of the myocardium also reduces oxygen demand which provides therapeutic benefit by reducing the mismatch of oxygen supply and demand in settings where coronary blood flow is limited, such as in coronary atherosclerosis. Reducing oxygen demand, particularly due to exercise, can reduce the frequency of angina pectoris symptoms and potentially improve survival of the remaining myocardium after myocardial infarction. The decrease in rate of sinoatrial node potentials, electrical conduction, slowing of potentials traveling through the atrioventricular node, and reduced frequency of ectopic potentials due to blockade of adrenergic beta receptors has led to benefit in arrhythmic conditions such as atrial fibrillation by controlling the rate of action potential generation and allowing for more effective coordinated contractions. Since a degree of sympathetic activity is necessary to maintain cardiac function, the reduced contractility induced by atenolol may precipitate or worsen heart failure, especially during volume overload.LabelThe effects of atenolol on blood pressure have been established, although it is less effective than alternative beta-blockers, but the mechanism has not yet been characterized.Label,24As a β1 selective drug, it does not act via the vasodilation produced by non-selective agents.24Despite this there is a sustained reduction in peripheral vascular resistance, and consequently blood pressure, alongside a decrease in cardiac output. It is thought that atenolol's antihypertensive activity may be related to action on the central nervous system (CNS) or it's inhibition of the renin-aldosterone-angiotensin system rather than direct effects on the vasculature.LabelAtenolol produces CNS effects similar to other beta-blockers, but does so to a lesser extent due to reduces ability to cross the blood-brain barrier.24It has the potential to produce fatigue, depression, and sleep disturbances such as nightmares or insomnia.Label,24The exact mechanisms behind these have not been characterized but their occurrence must be considered as they represent clinically relevant adverse effects.Atenolol exerts some effects on the respiratory system although to a much lesser extent than non-selective beta-blockers.LabelInteraction with β2 receptors in the airways can produce bronchoconstriction by blocking the relaxation of bronchial smooth muscle mediated by the sympathetic nervous system.24The same action can interfere with β-agonist therapies used in asthma and chronic obstructive pulmonary disease.Label,14,24Unlike some other beta-blocker drugs, atenolol does not have intrinsic sympathomimetic or membrane stabilizing activity nor does it produce changes in glycemic control.Label",CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1,"Atenolol is a cardioselective beta-blocker, called such because it selectively binds to the β-adrenergic receptor as an antagonist up to a reported fold more than β receptors.Selective activity at the β receptor produces cardioselectivity due to the higher population of this receptor in cardiac tissue. Some binding to β and possibly β receptors can still occur at therapeutic dosages but the effects mediated by antagonizing these are significantly reduced from those of non-selective agents. β and β receptors are Gscoupled therefore antagonism of their activation reduces activity of adenylyl cyclase and its downstream signalling via cyclic adenosime monophosphate and protein kinase A (PKA).In cardiomyocytes PKA is thought to mediate activation of L-type calcium channels and ryanodine receptors through their phosphorylation.L-type calcium channels can then provide an initial rise in intracellular calcium and trigger the ryanodine receptors to release calcium stored in the sarcoplasmic reticulum (SR) and increased contractility. PKA also plays a role in the cessation of contraction by phosphorylating phospholamban which in turn increases the affinity of SR Ca+ATPase to increase reuptake of calcium into the SR. It also phophorylates troponin I to reduce affinity of the protein for calcium. Both of these events lead to a reduction in contraction which, when coupled with the initial increase in contraction, allows for faster cycling and consequently higher heart rate with increased contractility. L-type calcium channels are also a major contributor to cardiac depolarization and their activation can increase frequency of action potentials and possibly the incidence of ectopic potentials.Similar inihibitory events occur in the bronchial smooth muscle to mediate relaxation including phosphorylation of myosin light-chain kinase, reducing its affinity for calcium.PKA also inhibits the excitatory Gqcoupled pathway by phosphorylating the inositol trisphosphate receptor and phospholipase C resulting in inhibition of intracellular calcium release. Antagonism of this activity by beta-blocker agents like atenolol can thus cause increased bronchoconstriction.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Beta blocking agents and calcium channel blockers', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Selective', 'Beta Blocking Agents, Selective, and Thiazides', 'Beta-Blockers (Beta1 Selective)', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Peripheral Nervous System Agents', 'QTc shortening agents', 'Sympatholytics']" +DB00531,Cyclophosphamide,"Cyclophosphamideis a nitrogen mustard used to treat lymphomas, myelomas, leukemia, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma.",['O75469'],"Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.",ClCCN(CCCl)P1(=O)NCCCO1,"Alkylating agents work by three different mechanisms: ) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, ) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and ) the induction of mispairing of the nucleotides leading to mutations.TargetActionsOrganismADNAcross-linking/alkylationHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Hydrocarbons, Halogenated', 'Immunologic Factors', 'Immunosuppressive Agents', 'Methemoglobinemia Associated Agents', 'Mustard Compounds', 'Mutagens', 'Myeloablative Agonists', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Neurotoxic agents', 'Nitrogen Mustard Analogues', 'Nitrogen Mustard Compounds', 'Noxae', 'Organophosphorus Compounds', 'Phosphoramide Mustards', 'Phosphoramides', 'Toxic Actions']" +DB00315,Zolmitriptan,Zolmitriptanis a member of the triptan class of 5-HT(1B/1D/1F) receptor agonist drugs used for the acute treatment of migraine with or without aura in adults.,"['P28222', 'P28221', 'P30939', 'P28566', 'P34969', 'P08908', 'P28223', 'P41595']","Zolmitriptan, like other triptans, is a serotonin (5-hydroxytryptamine; 5-HT) receptor agonist, with enhanced specificity for the 5-HT1Band 5-HT1Dreceptor subtypes. It is through the downstream effects of 5-HT1B/1Dactivation that triptans are proposed to provide acute relief of migraines.14,1,2Zolmitriptan is also a vasoconstrictor,5leading to possible adverse cardiovascular effects such as myocardial ischemia/infarction, arrhythmias, cerebral and subarachnoid hemorrhage, stroke, gastrointestinal ischemia, and peripheral vasospastic reactions. In addition, chest/throat/neck/jaw pain, tightness, and/or pressure has been reported, along with the possibility of medication overuse headaches and serotonin syndrome. Patients with phenylketonuria should be advised that ZOMIG-ZMT contains phenylalanine.14",CN(C)CCC1=CNC2=CC=C(C[C@H]3COC(=O)N3)C=C12,"Migraines are complex physiological events characterized by unilateral throbbing headaches combined with photophobia and other aversions to sensory input. Migraine attacks are generally divided into phases: the premonitory phase, which typically involves irritability, fatigue, yawning, and stiff neck; the headache phase, which lasts for between four and hours; and the postdrome phase, which lasts for up to a day following resolution of pain and whose symptoms are similar to those of the premonitory phase. In addition, neurological deficits, collectively termed migraine aura, may precede the headache phase.,The underlying pathophysiology of migraines is a matter of active research but involves both neurological and vascular components. The head pain associated with migraine is thought to be a consequence of activation of the nociceptive nerves comprising the trigeminocervical complex (TCC).Terminals of nociceptive nerves that innervate the dura matter release vasoactive peptides, such as calcitonin gene-related peptide (CGRP), resulting in cranial vasodilation. Finally, when present, migraine aura appears to correlate with a transient wave(s) of cortical depolarization, termed cortical spreading depression (CSD).,Triptans, including zolmitriptan, are proposed to act in three ways. The main mechanism is through modulation of nociceptive nerve signalling in the central nervous system through -HTB/Dreceptors throughout the TCC and associated areas of the brain. In addition, triptans can enhance vasoconstriction, both through direct -HTB-mediated dilation of cranial blood vessels,,as well as through -HTD-mediated suppression of CGRP release.,Although triptans are classically described solely in terms of their effects on -HTB/Dreceptors, they also act as -HTFagonists as well. This -HT subtype is also found throughout the TCC, but is not present appreciably in cerebral vasculature; the significance of triptan-mediated -HTFactivation is currently not well described.Additionally, CSD that initiates in the ipsilateral parietal region may exert its effects in a manner that relies on -HTB/Dreceptor activation, suggesting that triptans may have some effect on CSD-mediated symptoms.,TargetActionsOrganismA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor FagonistHumansU-hydroxytryptamine receptor EagonistHumansN-hydroxytryptamine receptor agonistHumansN-hydroxytryptamine receptor AagonistHumansN-hydroxytryptamine receptor AagonistHumansN-hydroxytryptamine receptor BagonistHumans",[],"['Agents that produce hypertension', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Biogenic Amines', 'Biogenic Monoamines', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Monoamine Oxidase A Substrates', 'Nervous System', 'Neurotransmitter Agents', 'Oxazoles', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Triptans']" +DB00343,Diltiazem,Diltiazemis a calcium channel blocker used to treat hypertension and to manage chronic stable angina.,"['Q13936', 'Q06432']","Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.12Diltiazem inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Diltiazem is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate).9It is also considered a rate-control drug as it reduces heart rate.2,8Diltiazem is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow.10Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations.12In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.10As the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension. In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo.12In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed.2When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients.2",COC1=CC=C(C=C1)[C@@H]1SC2=C(C=CC=C2)N(CCN(C)C)C(=O)[C@@H]1OC(C)=O,"Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channelsassociated with a high activation threshold and slow inactivation profile.L-type calcium channels are the main current responsible for the late phase of the pacemaker potential.Acting as the main Ca+ source for contraction in smooth and cardiac muscle, activation of L-type calcium channels allows the influx of calcium ions into the muscles upon depolarization and excitation of the channel.It is proposed that this cation influx may also trigger the release of additional calcium ions from intracellular storage sites.Diltiazem is a slow calcium channel blocker that binds to the extracellular site of the alpha-C subunit of the channel, which is thought to be the S- linker region of the transmembrane domain IV and/or S segment of domain III.Diltiazem can get access to this binding site from either the intracellular or extracellular side, but it requires a voltage-induced conformational changes in the membrane.Diltiazem inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes.In isolated human atrial and ventricular myocardium, diltiazem suppressed tension over the range of membrane potentials associated with calcium channel activity but had little effect on the tension-voltage relations at more positive potentials.This effect is thought to be mediated by the voltage-dependent block of the L-type calcium channels and inhibition of calcium ion release from the ER stores, without altering the sodium-calcium coupled transport or calcium sensitivity of myofilaments.Through inhibition of inward calcium current, diltiazem exerts a direct ionotropic and energy sparing effect on the myocardium.Diltiazem fslows atrioventricular nodal conduction, which is due to its ability to impede slow channel function.Reduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and therefore, decreased blood pressure.The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.,Through its actions on reducing calcium levels in cardiac and vascular smooth muscles, diltiazem causes a reduction in the contractile processes of the myocardial smooth muscle cells and vasodilation of the coronary and systemic arteries, including epicardial and subendocardial. This subsequently leads to increased oxygen delivery to the myocardial tissue, improved cardiac output due to increased stroke volume, decreased total peripheral resistance, decreased systemic blood pressure and heart rate, and decreased afterload.,Diltiazem lowers myocardial oxygen demand through a reduction in heart rate, blood pressure, and cardiac contractility; this leads to a therapeutic effect in improving exercise tolerance in chronic stable angina.,TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CblockerHumansAVoltage-dependent calcium channel gamma- subunitblockerHumans",[],"['Agents causing hyperkalemia', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzazepines', 'Benzothiazepine Derivatives', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Nondihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Miscellaneous Calcium-channel Blocking Agents', 'Moderate Risk QTc-Prolonging Agents', 'Negative Inotrope', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Direct Cardiac Effects', 'Vasodilating Agents', 'Vasoprotectives']" +DB00544,Fluorouracil,"Fluorouracilis a pyrimidine analog used to treat basal cell carcinomas, and as an injection in palliative cancer treatment.",['P04818'],"Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the ""S"" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.",FC1=CNC(=O)NC1=O,"The precise mechanism of action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N–-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.TargetActionsOrganismADNAincorporation into and destabilizationHumansARNAincorporation into and destabilizationHumansAThymidylate synthaseother/unknownHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Fluoropyrimidines', 'Fluorouracil and prodrugs', 'Immunologic Factors', 'Immunosuppressive Agents', 'Misc. Skin and Mucous Membrane Agents', 'Moderate Risk QTc-Prolonging Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleoside Metabolic Inhibitor', 'Photosensitizing Agents', 'Pyrimidine Analogues', 'Pyrimidines', 'Pyrimidinones', 'QTc Prolonging Agents', 'Thyroxine-binding globulin inducers', 'Toxic Actions']" +DB01169,Arsenic trioxide,Arsenic trioxideis a chemotherapeutic agent used in the treatment of refractory or relapsed acute promyelocytic leukemia in patients with prior retinoid and anthracycline chemotherapy.,"['O14920', 'Q16881', 'P05412', 'P24385', 'P27361', 'P28482', 'P31749', 'P38936', 'Q13547', 'P29590']","Arsenic Trioxide is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy.",O=[As]O[As]=O,"The mechanism of action of Arsenic Trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB human promyelocytic leukemia cellsin vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR-alpha. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis.TargetActionsOrganismAInhibitor of nuclear factor kappa-B kinase subunit betainducerHumansAThioredoxin reductase , cytoplasmicinhibitorHumansATranscription factor AP-inducerHumansAG/S-specific cyclin-DantagonistHumansAMitogen-activated protein kinase inducerHumansAMitogen-activated protein kinase inducerHumansURAC-alpha serine/threonine-protein kinaseinducerHumansUCyclin-dependent kinase inhibitor Not AvailableHumansUHistone deacetylase Not AvailableHumansUProtein PMLNot AvailableHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Arsenicals', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Highest Risk QTc-Prolonging Agents', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Oxides', 'Oxygen Compounds', 'P-glycoprotein inhibitors', 'QTc Prolonging Agents']" +DB01394,Colchicine,Colchicineis an alkaloid used to treat gout and Familial Mediterranean Fever as well as prevent major cardiovascular events.,['P07437'],"Colchicine ameliorates the symptoms of gout and Familial Mediterranean fever.1,9It possesses anti-inflammatory, anti-fibrotic, and cardiovascular protective effects. Colchicine was shown to exhibit anticancer properties, such as the inhibition of cancer cell migration and angiogenesis. Colchicine has a narrow therapeutic window.1",COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1[C@H](CC2)NC(C)=O,"The exact mechanism of action of colchicine has not been fully established; however, colchicine likely interferes with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-β, an inflammatory mediator.,,Colchicine also attenuates neutrophil adhesion and recruitment, as well as superoxide production.Clinical data demonstrate that colchicine reduces high-sensitivity C- reactive protein (hs-CRP).Colchicine is an anti-mitotic drug that disrupts cytoskeletal functions by inhibiting β-tubulin polymerization into microtubules. Consequently, it prevents the activation, degranulation, and migration of neutrophils. This pharmacological action is thought to be related to colchicine ameliorating gout symptoms and preventing major cardiovascular events.,Colchicine blocks microtubule growth at low concentrations and causes the depolymerization of microtubules at high concentrations.TargetActionsOrganismATubulin beta chaininhibitorbinderHumans",[],"['Agents Causing Muscle Toxicity', 'Alkaloids', 'Antigout Preparations', 'Antimitotic Agents', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Experimental Unapproved Treatments for COVID-19', 'Mitosis Modulators', 'Musculo-Skeletal System', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Preparations With No Effect on Uric Acid Metabolism', 'Tubulin Modulators']" +DB00608,Chloroquine,"Chloroquineis an antimalarial drug used to treat susceptible infections with P. vivax, P. malariae, P. ovale, and P. falciparum. It is also used for second line treatment for rheumatoid arthritis.","['P09210', 'P01375', 'Q9NR96', 'Q8ILQ7', 'P09429', 'P09488', 'Q9BYF1']","Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme inPlasmodiumspecies.11It has a long duration of action as the half life is 20-60 days.10Patients should be counselled regarding the risk of retinopathy with long term usage or high dosage, muscle weakness, and toxicity in children.19",CCN(CC)CCCC(C)NC1=CC=NC2=CC(Cl)=CC=C12,"Chloroquine inhibits the action of heme polymerase in malarial trophozoites, preventing the conversion of heme to hemazoin.,,Plasmodiumspecies continue to accumulate toxic heme, killing the parasite.Chloroquine passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH.,The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell.Chloroquine does not affect the level of ACE expression on cell surfaces, but inhibits terminal glycosylation of ACE, the receptor that SARS-CoV and SARS-CoV- target for cell entry.,ACE that is not in the glycosylated state may less efficiently interact with the SARS-CoV- spike protein, further inhibiting viral entry.TargetActionsOrganismUGlutathione S-transferase AinhibitorHumansUTumor necrosis factorinhibitorHumansUToll-like receptor inhibitorHumansUGlutathione S-transferaseinhibitorPlasmodium falciparumUHigh mobility group protein BinhibitorHumansUGlutathione S-transferase Mu inhibitorHumansUAngiotensin-converting enzyme modulatorHumans",[],"['Agents Causing Muscle Toxicity', 'Agents that produce neuromuscular block (indirect)', 'Agents that reduce seizure threshold', 'alpha-Galactosidase, antagonists & inhibitors', 'Amebicides', 'Aminoquinolines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Infective Agents', 'Anti-Inflammatory Agents', 'Antimalarials', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Antirheumatic Agents', 'Biguanides', 'Central Nervous System Agents', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Experimental Unapproved Treatments for COVID-19', 'Filaricides', 'Heterocyclic Compounds, Fused-Ring', 'Methemoglobinemia Associated Agents', 'Moderate Risk QTc-Prolonging Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Quinolines', 'Sensory System Agents', 'Tumor Necrosis Factor Blockers']" +DB00313,Valproic acid,Valproic acidis an anticonvulsant used to control complex partial seizures and both simple and complex absence seizures.,"['Q9UKV0', 'P45954', 'Q02218', 'P51649', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q07699', 'O60939', 'Q9NY72', 'Q8IWT1', 'Q92769', 'Q07869', 'Q03181', 'P37231', 'Q13547', 'Q969S8', 'Q96DB2', 'Q92769', 'O15379', 'P56524', 'Q9UQL6', 'Q9UBN7', 'Q8WUI4', 'Q9BY41', 'Q9UKV0', 'P38936', 'P14210', 'P11926', 'Q9NZQ7']","Valproate has been shown to reduce the incidence of complex partial seizures and migraine headaches.Label,5It also improves symptom control in bipolar mania.23Although the exact mechanisms responsible are unknown, it is thought that valproate produces increased cortical inhibition to contribute to control of neural synchrony. It is also thought that valproate exerts a neuroprotective effect preventing damage and neural degeneration in epilepsy, migraines, and bipolar disorder.Valproate is hepatotoxic and teratogenic. The reasons for this are unclear but have been attributed to the genomic effects of the drug.1A small proof-of concept study found that valproate increases clearance of human immunodeficiency virus (HIV) when combined with highly active antiretroviral therapy (HAART) by reactivating the virus to allow clearance, however, a larger multicentre trial failed to show a significant effect on HIV reservoirs when added to HAART.2,6The FDA labeling contains a warning regarding HIV reactivation during valproate use.Label.",CCCC(CCC)C(O)=O,"The exact mechanisms by which valproate exerts it's effects on epilepsy, migraine headaches, and bipolar disorder are unknown however several pathways exist which may contribute to the drug's action.Valproate is known to inhibit succinic semialdehyde dehydrogenase.This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase ultimately reducing GABA metabolism and increasing GABAergic neurotransmission. As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity.A possible secondary contributor to cortical inhibition is a direct suppression of voltage gated sodium channel activity and indirect suppression through effects on GABA.It has also been suggested that valproate impacts the extracellular signal-related kinase pathway (ERK).These effects appear to be dependent on mitogen-activated protein kinase (MEK) and result in the phosphorylation of ERK/. This activation increases expression of several downstream targets including ELK- with subsequent increases in c-fos, growth cone-associated protein- which contributes to neural plasticity, B-cell lymphoma/leukaemia- which is an anti-apoptotic protein, and brain-derived neurotrophic factor (BDNF) which is also involved in neural plasticity and growth. Increased neurogenesis and neurite growth due to valproate are attributed to the effects of this pathway. An additional downstream effect of increased BDNF expression appears to be an increase in GABAAreceptors which contribute further to increased GABAergic activity.Valproate exerts a non-competitive indirect inhibitory effect on myo-inosital--phophate synthetase.This results in reduced de novo synthesis of inositol monophosphatase and subsequent inositol depletion. It is unknown how this contributed to valproate's effects on bipolar disorder but [lithium] is known to exert a similar inositol-depleting effect.Valproate exposure also appears to produce down-regulation of protein kinase C proteins (PKC)-α and -ε which are potentially related to bipolar disorder as PKC is unregulated in the frontal cortex of bipolar patients. This is further supported by a similar reduction in PKC with lithium.The inhibition of the PKC pathway may also be a contributor to migraine prophylaxis.Myristoylated alanine-rich C kinase substrate, a PKC substrate, is also downregulated by valproate and may contribute to changes in synaptic remodeling through effects on the cytoskeleton.Valproate also appears to impact fatty acid metabolism.Less incorporation of fatty acid substrates in sterols and glycerolipids is thought to impact membrane fluidity and result in increased action potential threshold potentially contributing to valproate's antiepileptic action.Valproate has been found to be a non-competitive direct inhibitor of brain microsomal long-chain fatty acyl-CoA synthetase.Inhibition of this enzyme decreases available arichidonyl-CoA, a substrate in the production of inflammatory prostaglandins. It is thought that this may be a mechanism behind valproate's efficacy in migraine prophylaxis as migraines are routinely treated with non-steroidal anti-inflammatory drugs which also inhibit prostaglandin production.Finally, valproate acts as a direct histone deactylase (HDAC) inhibitor.Hyperacetylation of lysine residues on histones promoted DNA relaxation and allows for increased gene transcription. The scope of valproate's genomic effects is wide with genes being up or down-regulated.The relation of these genomic effects to therapeutic value is not fully characterized however H and H hyperacetylation correlates with improvement of symptoms in bipolar patients.Histone hyperacetylation at the BDNF gene, increasing BDNF expression, post-seizure is known to occur and is thought to be a neuroprotective mechanism which valproate may strengthen or prolong.H hyperacetylation is associated with a reduction in glyceraldehyde--phosphate dehydrogenase, a pro-apoptotic enzyme, contributing further to valproate's neuroprotective effects.TargetActionsOrganismAHistone deacetylase inhibitorHumansUShort/branched chain specific acyl-CoA dehydrogenase, mitochondrialinhibitorHumansU-oxoglutarate dehydrogenase, mitochondrialinhibitorHumansUSuccinate-semialdehyde dehydrogenase, mitochondrialinhibitorHumansUSodium channel proteininhibitorHumansUHistone deacetylase inhibitorHumansUPeroxisome proliferator-activated receptor alphaNot AvailableHumansUPeroxisome proliferator-activated receptor deltaNot AvailableHumansUPeroxisome proliferator-activated receptor gammaNot AvailableHumansUHistone deacetylaseinhibitorHumansUCyclin-dependent kinase inhibitor regulatorHumansUHepatocyte growth factorinhibitorHumansUOrnithine decarboxylasedownregulatorHumansUProgrammed cell death ligand downregulatorHumans",[],"['Acids, Acyclic', 'Anti-epileptic Agent', 'Anticonvulsants', 'Antimanic Agents', 'Antineoplastic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Fatty Acid Derivatives', 'Fatty Acids', 'Fatty Acids, Volatile', 'GABA Agents', 'Hepatotoxic Agents', 'Highest Risk QTc-Prolonging Agents', 'Histone Deacetylase Inhibitors', 'Lipids', 'Methemoglobinemia Associated Agents', 'Miscellaneous Anticonvulsants', 'Mood Stabilizer', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Pentanoic Acids', 'Photosensitizing Agents', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Tranquilizing Agents', 'UGT1A1 Inhibitors', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index', 'UGT1A3 substrates', 'UGT1A3 Substrates with a Narrow Therapeutic Index', 'UGT1A4 substrates', 'UGT1A6 substrate', 'UGT1A6 Substrates with a Narrow Therapeutic Index', 'UGT1A9 Substrates', 'UGT1A9 Substrates with a Narrow Therapeutic Index', 'UGT2B7 substrates', 'UGT2B7 Substrates with a Narrow Therapeutic Index', 'Valerates']" +DB00570,Vinblastine,"Vinblastineis a vinca alkaloid used to treat breast cancer, testicular cancer, neuroblastoma, Hodgkin's and non-Hodgkins lymphoma, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.","['Q71U36', 'P07437', 'Q9UJT1', 'P23258', 'Q9UJT0', 'P05412']","Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units: vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effectsin vitro. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.",[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@@](CC)([C@@H](OC(C)=O)[C@]2(O)C(=O)OC)[C@@]13[H])[C@]1(C[C@@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=C2C=CC=C1)C(=O)OC,"The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.TargetActionsOrganismATubulin alpha-A chainbinderHumansATubulin beta chainbinderHumansATubulin delta chainbinderHumansATubulin gamma- chainbinderHumansATubulin epsilon chainbinderHumansNTranscription factor AP-other/unknownHumans",[],"['Alkaloids', 'Antimitotic Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Mitosis Modulators', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Secologanin Tryptamine Alkaloids', 'Tubulin Modulators', 'Vinca Alkaloids']" +DB00501,Cimetidine,"Cimetidineis a histamine H2 receptor antagonist used to manage GERD, peptic ulcer disease, and indigestion.",['P25021'],"Cimetidine is a histamine H2-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms.",CN\C(NCCSCC1=C(C)NC=N1)=N\C#N,"Cimetidine binds to an H-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Acid Reducers', 'Adjuvants', 'Agents Causing Muscle Toxicity', 'Alimentary Tract and Metabolism', 'Amidines', 'Anti-Ulcer Agents', 'BSEP/ABCB11 Inhibitors', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Guanidines', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H2 Antagonists', 'Imidazoles', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 2 Inhibitors', 'MATE 2 Substrates', 'MATE inhibitors', 'MATE substrates', 'Neurotransmitter Agents', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'P-glycoprotein inducers', 'P-glycoprotein substrates']" +DB00563,Methotrexate,"Methotrexateis an antineoplastic agent used the treatment of a wide variety of cancers as well as severe psoriasis, severe rheumatoid arthritis, and juvenile rheumatoid arthritis.","['P04818', 'P31939', 'P00374']","Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions.1It has a long duration of action and is generally given to patients once weekly.1,4,5,6Methotrexate has a narrow therapeutic index.2Do not take methotrexate daily.5,6",CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O,"Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate.Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase.Inhibtion of nucleotide synthesis prevents cell division.In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate.This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.TargetActionsOrganismAThymidylate synthaseinhibitorHumansABifunctional purine biosynthesis protein PURHinhibitorHumansADihydrofolate reductaseinhibitorHumans",['Medically induced abortion'],"['Abortifacient Agents', 'Abortifacient Agents, Nonsteroidal', 'Agents Causing Muscle Toxicity', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'BCRP/ABCG2 Substrates', 'Biological Factors', 'Cancer immunotherapy', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Folic Acid Analogues', 'Folic Acid Antagonists', 'Hepatotoxic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Immunosuppressive Agents', 'Immunotherapy', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Pigments, Biological', 'Pteridines', 'Pterins', 'Reproductive Control Agents', 'Toxic Actions']" +DB02709,Resveratrol,"Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic phytoalexin. It is a stilbenoid, a derivate of stilbene, and is produced in plants with the help of the enzyme stilbene synthase. It exists as cis-(Z) and trans-(E) isomers. The trans- form can undergo isomerisation to the cis- form when heated or exposed to ultraviolet irradiation. In a 2004 issue of Science, Dr. Sinclair of Harvard University said resveratrol is not an easy molecule to protect from oxidation. It has been claimed that it is readily degraded by exposure to light, heat, and oxygen. However, studies find that Trans-resveratrol undergoes negligible oxidation in normal atmosphere at room temperature.","['P16083', 'P68400', 'P23219', 'P35354', 'P16050', 'P09917', 'P35869', 'Q8TCG2', 'P08648', 'P05106', 'P05067', 'P37840', 'Q96EB6', 'P03372', 'P48039', 'P49286', 'Q86T13', 'O75469', 'Q14994', 'P11166', 'P16152', 'Q07869', 'P37231', 'P31749', 'Q92945', 'P54577']","Resveratrol, a phytoalexin, has been found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner, although this is only one of its many pharmaceutical properties. In some countries where there is higher consumption of red wine, there appears to be a lower incidence of heart disease. Other benefits of resveratrol include its anti-inflammatory and antioxidant effects. In preclinical studies, Resveratrol has been found to have potential anticancer properties.",OC1=CC=C(\C=C\C2=CC(O)=CC(O)=C2)C=C1,"Resveratrol suppresses NF-kappaB (NF-kappaB) activation in HSV infected cells. Reports have indicated that HSV activates NF-kappaB during productive infection and this may be an essential aspect of its replication scheme [PMID: ].TargetActionsOrganismURibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHumansUCasein kinase II subunit alphaNot AvailableHumansUProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumansUArachidonate -lipoxygenaseNot AvailableHumansUArachidonate -lipoxygenaseNot AvailableHumansUAryl hydrocarbon receptorNot AvailableHumansUPhosphatidylinositol -kinase type -betaNot AvailableHumansUIntegrin alpha-Not AvailableHumansUIntegrin beta-Not AvailableHumansUAmyloid beta A proteinNot AvailableHumansUAlpha-synucleinNot AvailableHumansUNAD-dependent protein deacetylase sirtuin-Not AvailableHumansUEstrogen receptor alphaNot AvailableHumansUMelatonin receptor type ANot AvailableHumansUMelatonin receptor type BNot AvailableHumansUC-type lectin domain family member ANot AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumansUSolute carrier family , facilitated glucose transporter member Not AvailableHumansUCarbonyl reductase [NADPH] inhibitorHumansUPeroxisome proliferator-activated receptor alphaNot AvailableHumansUPeroxisome proliferator-activated receptor gammaNot AvailableHumansURAC-alpha serine/threonine-protein kinaseinhibitorHumansUFar upstream element-binding protein Not AvailableHumansUTyrosine--tRNA ligase, cytoplasmicinhibitorHumans",[],"['Angiogenesis Inhibitors', 'Anticarcinogenic Agents', 'Antioxidants', 'Antiplatelet agents', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzylidene Compounds', 'Biological Factors', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Hematologic Agents', 'Phenols', 'Polyphenols', 'Protective Agents', 'Stilbenes', 'Stilbestrols', 'Vasodilating Agents']" +DB00437,Allopurinol,"Allopurinolis a xanthine oxidase inhibitor used to reduce urinary and serum uric acid concentrations in patients with gout, recurrent calcium oxalate calculi, and various malignancies.",['P47989'],"Allopurinol decreases the production of uric acid by stopping the biochemical reactions that precede its formationLabel. This process decreases urate and relieves the symptoms of gout, which may include painful tophi, joint pain, inflammation, redness, decreased range of motion, and swelling2.",OC1=NC=NC2=C1C=NN2,"Allopurinol is a structural analog of the natural purine base, hypoxanthine. After ingestion, allopurinol is metabolized to its active metabolite, oxypurinol (alloxanthine) in the liver, which acts as an inhibitor of xanthine oxidase enzymeLabel.Allopurinol and its active metabolite inhibit xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Inhibition of this enzyme is responsible for the effects of allopurinol. This drug increases the reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis by a process that involves the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). This process results in an increased nucleotide concentration, which causes feedback inhibition of de novo purine synthesis. The end result is decreased urine and serum uric acid concentrations, which decreases the incidence of gout symptoms.Accompanying the reduction of serum uric acid by allopurinol is an increase in the serum and urine concentrations of hypoxanthine and xanthine (due to inhibition of xanthine oxidase). In the absence of allopurinol, regular urinary excretion of oxypurines almost entirely occurs in the form of uric acid. After the ingestion of allopurinol, the contents of excreted urine are hypoxanthine, xanthine, and uric acid. Because each substance has its own individual solubility, the concentration of uric acid in plasma is decreased without exposing the renal tissues to a high load of uric acid, thereby decreasing the risk of crystalluria. By lowering the uric acid concentration in the plasma below its limits of solubility, allopurinol encourages the dissolution of gout tophi. Although the levels of hypoxanthine and xanthine are found to be increased after allopurinol ingestion, the risk of deposition in renal tissues is less than that of uric acid, as they become more soluble and are rapidly excreted by the kidney.TargetActionsOrganismAXanthine dehydrogenase/oxidaseinhibitorHumans",[],"['Antigout Preparations', 'Antimetabolites', 'Antioxidants', 'BCRP/ABCG2 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Free Radical Scavengers', 'Heterocyclic Compounds, Fused-Ring', 'Musculo-Skeletal System', 'OAT3/SLC22A8 Substrates', 'Preparations Inhibiting Uric Acid Production', 'Protective Agents', 'Purines', 'Uricosuric Agents', 'Xanthine Oxidase Inhibitors']" +DB00541,Vincristine,"Vincristineis a vinca alkaloid used to treat acute leukemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, and acute panmyelosis.","['P07437', 'P68366']","Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effectsin vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.",[H][C@@]12N3CC[C@@]11C4=C(C=C(OC)C(=C4)[C@]4(C[C@H]5C[N@](C[C@](O)(CC)C5)CCC5=C4NC4=CC=CC=C54)C(=O)OC)N(C=O)[C@@]1([H])[C@](O)([C@H](OC(C)=O)[C@]2(CC)C=CC3)C(=O)OC,"The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: ) amino acid, cyclic AMP, and glutathione metabolism, ) calmodulin-dependent Ca+-transport ATPase activity, ) cellular respiration, and ) nucleic acid and lipid biosynthesis.TargetActionsOrganismATubulin beta chaininhibitorHumansUTubulin alpha-A chaininhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Alkaloids', 'Antimitotic Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Mitosis Modulators', 'Narrow Therapeutic Index Drugs', 'Neurotoxic agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Secologanin Tryptamine Alkaloids', 'Tubulin Modulators', 'Vinca Alkaloids']" +DB00682,Warfarin,"Warfarinis a vitamin K antagonist used to treat venous thromboembolism, pulmonary embolism, thromboembolism with atrial fibrillation, thromboembolism with cardiac valve replacement, and thromboembolic events post myocardial infarction.","['Q9BQB6', 'O75469']","Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and extent of thrombus formation.Label,17In patients with deep vein thrombosis or atrial fibrillation there is an increased risk of thrombus formation due to the reduced movement of blood.15For patients with cardiac valve disease or valve replacements this increased coagulability is due to tissue damage. Thrombi due to venous thrombosis can travel to the lungs and become pulmonary emboli, blocking circulation to a portion of lung tissue. Thrombi which form in the heart can travel to the brain and cause ischemic strokes. Prevention of these events is the primary goal of warfarin therapy.Limitation of thrombus formation is also a source of adverse effects. In patients with atheroscelotic plaques rupture typically results in thrombus formation.11When these patients are anticoagulated plaque rupture can allow the escape of cholesterol from the lipid core in the form of atheroemboli or cholesterol microemboli. These emboli are smaller than thrombi and block smaller vessels, usually less than 200 μm in diameter. The consequences of this are varied and depend on the location of the blockage. Effects include visual disturbances, acute kidney injury or worsening of chronic kidney disease, central nervous system ischemia, and purple or blue toe syndrome.Label,11Blue toe syndrome can be reversed if it has not progressed to tissue necrosis but the other effects of microemboli are often permanent.Antocoagulation appears to mediate warfarin-related nephropathy, a seemingly spontaneous kidney injury or worsening of chronic kidney disease associated with warfarin therapy.12Nephropathy in this case appears to be due to increased passage of red blood cells through the glomerulus and subsequent blockage of renal tubules with red blood cell casts. This is worsened or possibly triggered by pre-existing kidney damage. Increased risk of warfarin-related nephropathy occurs at INRs over 3.0 but risk does not increase as a function of INR beyond this point.Warfarin has been linked to the development of calciphylaxis.LabelThis is thought to be due to warfarin's inhibition ofvitamin Krecycling as VKA is needed for the carboxylation of matrix Gla protein.13This protein is an anti-calcification factor and its inhibition through preventing the carboxylation step in its production leads to a shift in calcification balance in favor of calciphylaxis.Tissue necrosis can occur early on in warfarin therapy.LabelThis is attributable to half lives of the clotting factors impacted by inhibition of vitamin K recycling.Label,14Proteins C and S are anticoagulation factors with half lives of 8 and 24 hours respectively. The coagulation factors IX, X, VII, and thrombin (factor II) have half lives of 24, 36, 6, and 50 hours respectively. This means proteins C and S are inactivated sooner than pro-coagulation proteins, with the exception of factor VII, resulting in a pro-thrombotic state for the first few days of therapy. Thrombi which form in this time period can occlude arterioles in various locations, blocking blood flow and causing tissue necrosis due to ischemia.",CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2,"Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase.Label,,The reduced form of vitamin K, vitamin KHis a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca+and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KHis converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin Kby vitamin K epoxide reductase then back to vitamin KHby vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of and hours, with the exception of factor VII which has a half life of hours.Factors IX, X, and finally thrombin degrade later with half lives of , , and hours resulting in a dominant anticoagulation effect.In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized.Label,,It takes approximately days for new coagulation factors to be synthesized in the liver. Vitamin K, functionally identical to vitamin K, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin KTargetActionsOrganismAVitamin K epoxide reductase complex subunit inhibitorHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['4-Hydroxycoumarins', 'Agrochemicals', 'Anticoagulants', 'Blood and Blood Forming Organs', 'Compounds used in a research, industrial, or household setting', 'Coumarins', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Pesticides', 'Pyrans', 'Rodenticides', 'Toxic Actions', 'Vitamin K Antagonists', 'Vitamin K Inhibitors']" +DB00413,Pramipexole,Pramipexoleis a non-ergot dopamine agonist used to treat the signs and symptoms of idiopathic Parkinson's disease and Restless Legs Syndrome (RLS).,"['P35462', 'P14416', 'P21917', 'P08908', 'P08913']","Parkinson's DiseaseThrough the stimulation of dopamine receptors, pramipexole is thought to relieve the symptoms of Parkinson's DiseaseLabel. The motor symptoms of Parkinson's disease occur partly due to a reduction of dopamine in the substantia nigra of the brain11. Dopamine is an essential neurotransmitter that has major effects on motor movements in humans.Restless Legs SyndromePramipexole likely restores balance to the dopaminergic system, controlling the symptoms of this condition. Restless legs syndrome is thought to occur, in part, through dysfunction of the dopaminergic system, resulting in unpleasant lower extremity symptoms9,15.Other effectsIn addition to the abovementioned effects, animal studies demonstrate that pramipexole blocks dopamine synthesis, release, and turnover. Additionally, this drug is neuroprotective to dopamine neuron degeneration after ischemia or methamphetamine neurotoxicity15.",CCCN[C@H]1CCC2=C(C1)SC(N)=N2,"The exact mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown at this time. It is thought, however, that the ability of pramipexole to cause stimulation of the dopamine receptors in the striatum of the brain, a region that receives a vast array of neurological input and is responsible for a wide variety of functions, may be involved. Studies performed in animals show that pramipexole influences striatal neuronal transmission rates following activation of dopamine receptorsLabel.Pramipexole is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D subfamily of dopamine receptors in vitro, binding selectively and dopamine D receptors and showing a preference for the dopamine D receptor subtype rather than other subtypes. The clinical significance of this binding specificity is unknownLabel,.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansUAlpha-A adrenergic receptoragonistHumans",[],"['Anti-Dyskinesia Agents', 'Anti-Parkinson Agents (Dopamine Agonist)', 'Anti-Parkinson Drugs', 'Antioxidants', 'Benzothiazoles', 'Biological Factors', 'Central Nervous System Agents', 'Dopamine Agents', 'Dopamine Agonists', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Nervous System', 'Neurotransmitter Agents', 'Nonergot-derivative Dopamine Receptor Agonists', 'OCT1 substrates', 'OCT2 Substrates', 'Restless Legs Syndrome', 'Sulfur Compounds', 'Thiazoles']" +DB01110,Miconazole,"Miconazoleis an azole antifungal with broad-spectrum activity used to treat fungal infections affecting the vagina, mouth and skin, including candidiasis.","['P10613', 'P29474', 'P35228', 'O75469', 'Q12791', 'Q16558', 'Q9Y691', 'Q9NPA1', 'Q86W47', 'O15554', 'Q92952', 'Q9H2S1', 'Q9UGI6', 'Q09470', 'Q16322', 'P16389', 'P22001', 'P22459', 'P22460', 'P17658', 'Q14721', 'Q92953', 'P48547', 'Q96PR1', 'Q14003', 'Q03721', 'Q9NSA2', 'Q9NZV8', 'Q9UK17', 'P15382', 'Q9Y6J6', 'Q9Y6H6', 'Q8WWG9', 'Q9UJ90', 'Q9H3M0', 'Q9UIX4', 'Q9UJ96', 'Q8TAE7', 'Q8TDN1', 'O95259', 'Q12809', 'Q9ULD8', 'Q9UQ05', 'Q8NCM2', 'Q9H252', 'Q9NS40', 'Q96L42', 'P51787', 'O43526', 'O43525', 'P56696', 'Q9NR82', 'Q96KK3', 'Q9BQ31', 'Q6PIU1', 'Q8TDN2', 'Q14722', 'Q13303', 'Q14500', 'Q9UNX9', 'P63252', 'P48050', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305']","Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex.3As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis.13Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.15",ClC1=CC(Cl)=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1,"Miconazole is an azole antifungal used to treat a variety of conditions, including those caused byCandidaovergrowth. Unique among the azoles, miconazole is thought to act through three main mechanisms.The primary mechanism of action is through inhibition of the CYP α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.,In addition, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to increased production of reactive oxygen species (ROS).,,Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis.Lastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing inCandida, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics.,In addition, farnesol is an inhibitor of drug efflux ABC transporters, namelyCandidaCaCdrp and CaCdrp, which may additionally contribute to increased effectiveness of azole drugs.TargetActionsOrganismACytochrome P inhibitorYeastUNitric oxide synthase, endothelialinhibitorHumansUNitric oxide synthase, inducibleinhibitorHumansUNuclear receptor subfamily group I member partial agonistHumansUCalcium-activated potassium channelinhibitorHumansUVoltage-gated Potassium ChannelsinhibitorUInward rectifier potassium channelinhibitorHumansUVoltage gated L-type calcium channelinhibitorHumans",[],"['14-alpha Demethylase Inhibitors', 'Anti-Infective Agents', 'Antifungal Agents', 'Antifungal Agents (Vaginal)', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Azole Antifungals', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strong)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazole and Triazole Derivatives', 'Imidazole Derivatives', 'Imidazoles', 'Intestinal Antiinfectives', 'Otologicals', 'P-glycoprotein inhibitors', 'Sensory Organs', 'Steroid Synthesis Inhibitors', 'Stomatological Preparations', 'Vaginal Creams, Foams, and Jellies']" +DB00582,Voriconazole,Voriconazoleis a triazole compound used to treat fungal infections.,['P10613'],Voriconazole is a fungistatic triazole antifungal used to treat infections by inhibiting fungal growth.13It is known to cause hepatotoxic and photosensitivity reactions in some patients.,C[C@@H](C1=NC=NC=C1F)[C@](O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1,"Voriconazole is used to treat fungal infections caused by a variety of organisms but includingAspergillus spp.andCandida spp. Voriconazole is a triazole antifungal exhibiting fungistatic activity against fungal pathogens.,,Like other triazoles, voriconazole binds to -alpha sterol demethylase, also known as CYP, and inhibits the demethylation of lanosterol as part of the ergosterol synthesis pathway in yeast and other fungi. The lack of sufficient ergosterol disrupts fungal cell membrane function and limits fungal cell growth. With fungal growth limited, the host's immune system is able to clear the invading organism.TargetActionsOrganismACytochrome P antagonistinhibitorYeast",[],"['14-alpha Demethylase Inhibitors', 'Anti-Infective Agents', 'Antifungal Agents', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Azole Antifungals', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Steroid Synthesis Inhibitors', 'Triazole and tetrazole derivatives', 'Triazole Derivatives', 'Triazoles']" +DB01167,Itraconazole,"Itraconazoleis an antifungal agent used for the treatment of various fungal infections in immunocompromised and non-immunocompromised patients, such as pulmonary and extrapulmonary blastomycosis, histoplasmosis, and onychomycosis.","['P50859', 'Q16850']","Itraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibitsin vitroactivity againstCryptococcus neoformansandCandida spp.Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due toCryptococcus neoformansand for systemic infections due toCandida albicans.",CCC(C)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@H]2CO[C@@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1,"Itraconazole interacts with -α demethylase, a cytochrome P- enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.TargetActionsOrganismALanosterol -alpha demethylaseinhibitorALanosterol -alpha demethylaseinhibitorHumans",[],"['14-alpha Demethylase Inhibitors', 'Agents causing hyperkalemia', 'Anti-Infective Agents', 'Antifungal Agents', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Azole Antifungals', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Piperazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Steroid Synthesis Inhibitors', 'Triazole and tetrazole derivatives', 'Triazole Derivatives', 'Triazoles']" +DB00196,Fluconazole,Fluconazoleis a triazole antifungal used to treat various fungal infections including candidiasis.,['P10613'],"Fluconazole has been demonstrated to show fungistatic activity against the majority of strains of the following microorganisms, curing fungal infections27:Candida albicans, Candida glabrata (Many strains are intermediately susceptible), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformansThis is achieved through steroidal inhibition in fungal cells, interfering with cell wall synthesis and growth as well as cell adhesion, thereby treating fungal infections and their symptoms.27,2,5The fungistatic activity of fluconazole has also been shown in normal and immunocompromised animal models with both systemic and intracranial fungal infections caused byCryptococcus neoformansand for systemic infections caused by Candida albicans.27It is important to note that resistant organisms have been found against various strains of organisms treated with fluconazole.11,12,13This further substantiates the need to perform susceptibility testing when fluconazole is considered as an antifungal therapy.14,20A note on steroidal effects of fluconazoleThere has been some concern that fluconazole may interfere with and inactivate human steroids/hormones due to the inhibition of hepatic cytochrome enzymes.26Fluconazole has demonstrated to be more selective forfungalcytochrome P-450 enzymes than for a variety of mammalian cytochrome P-450 enzymes. Fluconazole 50 mg administered daily for up to 28 days in individuals of reproductive age has been show to have no effect on testosterone plasma concentrations of males and plasma concentrations of steroids in females. A 200-400 mg dose of fluconazole showed no clinically relevant effect on steroid levels or on ACTH-stimulated steroid response in healthy males, in one clinical study mentioned on the European Medicines Agency label.26Other studies have shown no significant effects of fluconazole on steroid levels, further confirming these data.10,18",OC(CN1C=NC=N1)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1,"Fluconazole is a very selective inhibitor of fungal cytochrome P dependent enzymelanosterol -α-demethylase. This enzyme normally works to convertlanosteroltoergosterol, which is necessary for fungal cell wall synthesis. The free nitrogen atom located on the azole ring of fluconazole binds with a single iron atom located in the heme group of lanosterol -α-demethylase.This prevents oxygen activation and, as a result, inhibits the demethylation of lanosterol, halting the process of ergosterol biosynthesis.Methylated sterols are then found to accumulate in the fungal cellular membrane, leading to an arrest of fungal growth.These accumulated sterols negatively affect the structure and function of the fungal cell plasma membrane.Fluconazole resistance may arise from an alteration in the amount or function of the target enzyme (lanosterol -α-demethylase), altered access to this enzyme, or a combination of the above.Other mechanisms may also be implicated, and studies are ongoing.TargetActionsOrganismACytochrome P inhibitorYeast",[],"['14-alpha Demethylase Inhibitors', 'Agents causing hyperkalemia', 'Anti-Infective Agents', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Azole Antifungals', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazole and Triazole Derivatives', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Steroid Synthesis Inhibitors', 'Triazole and tetrazole derivatives', 'Triazole Derivatives', 'Triazoles']" +DB00242,Cladribine,"Cladribineis a purine antimetabolite used for the management of relapsing forms of Multiple Sclerosis (MS), used in patients who have not responded to or who were unable to tolerate alternative MS drugs.","['P23921', 'P31350', 'Q7LG56', 'P09884', 'Q07864', 'P56282', 'Q9NRF9', 'Q9NR33', 'P00491']","Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Cladribine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply.",NC1=C2N=CN([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC(Cl)=N1,"Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; -chloro-′-deoxyadenosine ′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established.TargetActionsOrganismARibonucleoside-diphosphate reductase large subunitinhibitorHumansARibonucleoside-diphosphate reductase subunit MinhibitorHumansARibonucleoside-diphosphate reductase subunit M BinhibitorHumansADNAother/unknownHumansADNA polymerase alpha catalytic subunitinhibitorHumansADNA polymerase epsilon catalytic subunit AinhibitorHumansADNA polymerase epsilon subunit inhibitorHumansADNA polymerase epsilon subunit inhibitorHumansADNA polymerase epsilon subunit inhibitorHumansAPurine nucleoside phosphorylaseinducerHumans",[],"['2-Chloroadenosine', 'Agents Causing Muscle Toxicity', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cardiotoxic antineoplastic agents', 'Deoxyadenosines', 'Deoxyribonucleosides', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Purine Analogues', 'Purine Antimetabolite', 'Purine Nucleosides', 'Purines', 'Ribonucleosides', 'Selective Immunosuppressants']" +DB01373,Calcium,Calciumis a mineral found in over-the-counter supplements or prescription formulations used for the treatment of specific medical conditions related to calcium deficiency.,"['Q13936', 'P98194', 'P02585', 'P63316', 'Q01082', 'P04271', 'P20810', 'P49747', 'P0DP23', 'P19801', 'Q99584', 'P05187', 'P05109', 'P06702', 'P29034', 'P00450', 'P12644', 'P08493', 'Q8TAB3', 'O75340']","Calcium (Ca2+) plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many enzymes require calcium ions as a cofactor, those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.",[Ca],"Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains % of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is , milligrams per day for women not taking estrogen and milligrams per day for women on estrogen. There is close to milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CligandHumansACalcium-transporting ATPase type C member agonistHumansATroponin C, skeletal muscleagonistHumansATroponin C, slow skeletal and cardiac musclesagonistHumansUSpectrin beta chain, non-erythrocytic agonistHumansUProtein S-BNot AvailableHumansUCalpastatinNot AvailableHumansUCartilage oligomeric matrix proteinNot AvailableHumansUCalmodulinNot AvailableHumansUAmiloride-sensitive amine oxidase [copper-containing]Not AvailableHumansUProtein S-ANot AvailableHumansUAlkaline phosphatase, placental typeNot AvailableHumansUProtein S-ANot AvailableHumansUProtein S-ANot AvailableHumansUProtein S-ANot AvailableHumansUCeruloplasminNot AvailableHumansUBone morphogenetic protein Not AvailableHumansUMatrix Gla proteinNot AvailableHumansUProtocadherin-Not AvailableHumansUProgrammed cell death protein Not AvailableHumans","['Care of the Joint', 'Mineral supplementation therapy', 'Nutritional supplementation']","['Alimentary Tract and Metabolism', 'Antacids and Adsorbents', 'Biological Factors', 'Blood Coagulation Factors', 'Calcium Salts', 'Calcium-Regulating Hormones and Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Elements', 'Metals', 'Metals, Alkaline Earth', 'Minerals', 'Musculo-Skeletal System', 'Phosphate Binder', 'Phosphate Chelating Activity', 'Replacement Preparations']" +DB00300,Tenofovir disoproxil,Tenofovir disoproxilis a nucleotide analog reverse transcriptase inhibitor used in the treatment of Hepatitis B infection and used in the management of HIV-1 infection.,"['Q72547', 'P24024']","This drug prevents viral DNA chain elongation through inhibition of enzymes necessary for host cell infection viral replication in HIV-1 and Hepatitis B infections9,10.In vitro effectsThe antiviral activity of tenofovir against in laboratory and clinical isolates of HIV-1 was studied in lymphoblastoid cell lines, primary monocyte/macrophage cells, in addition to peripheral blood lymphocytes. The EC50 (50% effective concentration) values of tenofovir against HIV-1 virus ranged between 0.04 μM to 8.5 μM.Combination of tenofovir disoproxil with other drugsIn drug combination studies of tenofovir with nucleoside reverse transcriptase inhibitors (abacavir, didanosine, lamivudine, stavudine, zalcitabine, zidovudine), non-nucleoside reverse transcriptase inhibitors (delavirdine, efavirenz, nevirapine), and protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir, saquinavir), additive and synergistic effects were seen. Tenofovir demonstrated antiviral activities in cell cultures against HIV-1Label.",[H][C@@](C)(CN1C=NC2=C(N)N=CN=C12)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C,"Tenofovir belongs to a class of antiretroviral drugs known as nucleotide analog reverse transcriptase inhibitors (NtRTIs), which block reverse transcriptase, an enzyme necessary for viral production in HIV-infected individuals. This enables the management of HIV viral load through decreased viral replicationLabel.Tenofovir disoproxil fumarate is the fumarate salt of the prodrugtenofovir disoproxil. Tenofovir disoproxil is absorbed and converted to its active form,tenofovir, a nucleoside monophosphate (nucleotide) analog. Tenofovir is then converted to the active metabolite,tenofovir diphosphate, a chain terminator, by constitutively expressed enzymes in the cell. Tenofovir diphosphate inhibits HIV- reverse transcriptase and the Hepatitis B polymerase by direct binding competition with the natural deoxyribonucleotide substrate (deoxyadenosine ’-triphosphate) and, after integration into DNA, causes viral DNA chain termination,Label.A note on resistanceHIV- isolates with decreased susceptibility to tenofovir have been identified in cell culture studies. These viruses expressed aKRsubstitution in reverse transcriptase and showed a – fold decrease in susceptibility to treatment with tenofovirLabel.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus UDNA polymerase/reverse transcriptaseinhibitorHBV-D",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Nephrotoxic agents', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Substrates', 'Organophosphorus Compounds', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Purines', 'Reverse Transcriptase Inhibitors', 'Tenofovir and prodrugs']" +DB01601,Lopinavir,Lopinaviris an HIV-1 protease inhibitor used in combination with ritonavir to treat human immunodeficiency virus (HIV) infection.,['Q72874'],"Lopinavir inhibits the activity of an enzyme critical for the HIV viral lifecycle.7It has a moderate duration of action necessitating once or twice daily dosing.7Lopinavir, like other protease inhibitors, has a propensity for participating in drug interactions - use caution when administering lopinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common. Fatal hepatotoxicity and pancreatitis have been noted in patients undergoing therapy with lopinavir and patients with an increased baseline risk of these events should be monitored closely throughout therapy.7",CC(C)[C@H](N1CCCNC1=O)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)COC1=C(C)C=CC=C1C)CC1=CC=CC=C1,"The HIV lifecycle is comprised of distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious.At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV- protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle.Lopinavir is an inhibitor of the HIV- protease enzyme.Its design is based on the ""peptidomimetic"" principle, wherein the molecule contains a hydroxyethylene scaffold which mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved.By preventing HIV- protease activity, and thus the proteolysis of the Gag polyprotein, lopinavir results in the production of immature, non-infectious viral particles.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'BSEP/ABCB11 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Experimental Unapproved Treatments for COVID-19', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'Nephrotoxic agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Protease Inhibitors', 'Pyrimidinones', 'QTc Prolonging Agents', 'Viral Protease Inhibitors']" +DB00900,Didanosine,Didanosineis a reverse transcriptase inhibitor used to treat HIV.,"['Q72547', 'P00491']","Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine is a hypoxanthine attached to the sugar ring, unlike other nucleoside analogues. Didanosine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid.",OC[C@@H]1CC[C@@H](O1)N1C=NC2=C1NC=NC2=O,"Didanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as the lack of a '-OH group in the incorporated nucleoside analogue prevents the formation of the ' to ' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus UPurine nucleoside phosphorylasesubstrateHumans",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Deoxyribonucleosides', 'Dideoxynucleosides', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Neurotoxic agents', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'OAT1/SLC22A6 Substrates', 'Purine Nucleosides', 'Purines', 'Reverse Transcriptase Inhibitors', 'Ribonucleosides', 'Toxic Actions']" +DB04743,Nimesulide,Nimesulideis a cyclooxygenase 2 inhibitor used to treat acute pain and primary dysmenorrhea.,"['P35354', 'Q9NZK7', 'P02788']","Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.",CS(=O)(=O)NC1=C(OC2=CC=CC=C2)C=C(C=C1)[N+]([O-])=O,"The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX- mediated prostaglandins, free radicals, proteolytic enzymes and histamine.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUGroup IIE secretory phospholipase ANot AvailableHumansULactotransferrinNot AvailableHumans",['NSAIDs'],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amides', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiarrhythmic agents', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antiplatelet agents', 'Antirheumatic Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Peripheral Nervous System Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Sulfones', 'Sulfur Compounds', 'Topical Products for Joint and Muscular Pain']" +DB09140,Oxygen,"Oxygenis an essential element for human survival used in clinical conditions in which there is a lack of oxygen, such as, but not limited to, anoxia, hypoxia or dyspnea.","['P00395', 'Q9Y5S8']","Oxygen therapy improves effective cellular oxygenation, even at a low rate of tissue perfusion. Oxygen molecules adjust hypoxic ventilatory drive by acting on chemoreceptors on carotid bodies that sequentially relay sensory information to the higher processing centers in brainstem. It also attenuates hypoxia-induced mitochondrial depolarization that generates reactive oxygen species and/or apoptosis. +Studies investigating on hyperbaric oxygen therapy has shown that oxygen supplementation can induce neural stem cell proliferation in neonatal rats thus promoting neurological regeneration after injuries3. CD34+, CD45-dim leukocytes are also potential targets for hyperbaric oxygen therapy benefit as their mobilization was increased in vitro which could facilitate the acceleration of recovery at peripheral sites1.",O=O,"Oxygen therapy increases the arterial pressure of oxygen and is effective in improving gas exchange and oxygen delivery to tissues, provided that there are functional alveolar units. Oxygen plays a critical role as an electron acceptor during oxidative phosphorylation in the electron transport chain through activation of cytochrome c oxidase (terminal enzyme of the electron transport chain). This process achieves successful aerobic respiration in organisms to generate ATP molecules as an energy source in many tissues. Oxygen supplementation acts to restore normal cellular activity at the mitochondrial level and reduce metabolic acidosis. There is also evidence that oxygen may interact with O-sensitive voltage-gated potassium channels in glomus cells and cause hyperpolarization of mitochondrial membrane.TargetActionsOrganismUCytochrome c oxidase subunit agonistactivatorHumansUNADPH oxidase agonistactivatorHumans",[],"['Chalcogens', 'Elements', 'Gases', 'Medical Gases', 'Miscellaneous Therapeutic Agents', 'Other Miscellaneous Therapeutic Agents']" +DB00907,Cocaine,Cocaineis an ester local anesthetic used during diagnostic procedures and surgeries in or through the nasal cavities.,"['Q01959', 'P23975', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q07699', 'O60939', 'Q9NY72', 'Q8IWT1', 'P31645', 'P11229', 'P08172', 'Q99720', 'P23141']","Cocaine is a local anesthetic indicated for the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.",[H][C@]12CC[C@]([H])([C@H]([C@H](C1)OC(=O)C1=CC=CC=C1)C(=O)OC)N2C,"Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Its effect on dopamine levels is most responsible for the addictive property of cocaine.TargetActionsOrganismASodium-dependent dopamine transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumansASodium channel proteininhibitorHumansASodium-dependent serotonin transporterinhibitorHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUSigma non-opioid intracellular receptor agonistHumansULiver carboxylesterase binderHumans",[],"['Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Alkaloids', 'Analgesics and Anesthetics', 'Anesthetics', 'Anesthetics, Local', 'Anticholinergic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Cholinesterase substrates', 'Cocaine, antagonists & inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Esters of Benzoic Acid', 'Highest Risk QTc-Prolonging Agents', 'Local Anesthetics (Ester)', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'OCT2 Inhibitors', 'Ophthalmologicals', 'QTc Prolonging Agents', 'Sensory Organs', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Throat Preparations', 'Tropanes', 'Vasoconstrictor Agents']" +DB00620,Triamcinolone,Triamcinoloneis a glucocorticoid used to treat a wide variety of inflammatory conditions of organ systems and tissues.,['P04150'],"Triamcinolone is a corticosteroid with anti-inflammatory properties.8These properties are used to treat inflammation in conditions that affect various organs and tissues.15Triamcinolone should not be administered as an epidural injection.10,12,13,15,16",[H][C@@]12C[C@@H](O)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Corticosteroids like triamcinolone inhibit phospholipase A on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes, which in turn prevent the formation of arachidonic acid, which decrease expression of cyclooxygenase and lipoxygenase, inhibiting synthesis of prostaglandins and leukotrienes.Anti-inflammatory activity occurs via reversal of vascular dilation and reducing permeability, which prevents macrophage and leukocyte migration.Triamcinolone also inhibits nuclear factor kappa-B, which decreases the production of pro-inflammatory signals such as interleukin-, interleukin-, and monocyte chemoattractant protein-.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents Causing Muscle Toxicity', 'Agents to Treat Airway Disease', 'Alimentary Tract and Metabolism', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids for Local Oral Treatment', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Moderately Potent (Group II)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs for Obstructive Airway Diseases', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunologic Factors', 'Immunosuppressive Agents', 'Nasal Preparations', 'Ophthalmologicals', 'Pregnadienes', 'Pregnanes', 'Protein-Lysine 6-Oxidase, antagonists & inhibitors', 'Sensory Organs', 'Steroids', 'Steroids, Fluorinated', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroxine-binding globulin inhibitors', 'Vasoprotectives']" +DB01217,Anastrozole,"Anastrozoleis a competitive, selective, non-steroidal aromatase inhibitor used as adjuvant therapy for the treatment of hormone receptor-positive breast cancer in postmenopausal women.",['P11511'],"Anastrozole prevents the conversion of adrenal androgens (e.g.testosterone) to estrogen in peripheral and tumour tissues. As the growth of many breast cancers is stimulated and/or maintained by the presence of estrogen, anastrozole helps to treat these cancers by decreasing the levels of circulating estrogens.12,9Anastrozole has a relatively long duration of action allowing for once daily dosing - serum estradiol is reduced by approximately 70% within 24 hours of beginning therapy with 1mg once daily, and levels remain suppressed for up to 6 days following cessation of therapy.10The incidence of ischemic cardiovascular events was increased during anastrozole therapy and patients with pre-existing ischemic heart disease should consider the risks and benefits of anastrozole before beginning therapy. Anastrozole has also been reported to decrease spine and hip bone mineral density (BMD), so consideration should be given to monitoring of BMD in patients receiving long-term therapy.10,8",CC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N,"Anastrazole exerts its anti-estrogenic effects via selective and competitive inhibition of the aromatase enzyme found predominantly in the adrenal glands, liver, and fatty tissues.Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone.In postmenopausal women, estrogen is primarily derived from the conversion of adrenally-produced androgens into estrogens by the aromatase enzyme - by competitively inhibiting the biosynthesis of estrogen at these enzymes, anastrozole effectively suppresses circulating estrogen levels and, subsequently, the growth of hormone receptor-positive tumours.,TargetActionsOrganismACytochrome P AinhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Aromatase Inhibitors', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Enzyme Inhibitors', 'Estrogen Antagonists', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Nitriles', 'P-glycoprotein substrates', 'Steroid Synthesis Inhibitors', 'Triazoles', 'UGT1A3 substrates', 'UGT1A4 substrates', 'UGT2B7 substrates']" +DB00624,Testosterone,"Testosteroneis a hormone used to treat hypogonadism, breast carcinoma in women, or the vasomotor symptoms of menopause.","['P10275', 'P03372', 'P08235']","Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics.5,14,15,16,17,18,19,20The duration of action of testosterone is variable from patient to patient with a half life of 10-100 minutes.14,15,16,17,18,19,20The therapeutic index is wide considering the normal testosterone levels in an adult man range from 300-1000ng/dL.14,16,17,18,19,20Counsel patients regarding the risk of secondary exposure of testosterone topical products to children.14,16,17,18,19",[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The androgen receptor exists in the cytoplasm bound to the heat shock proteins HSP, HSP, and other chaperones.After binding to an androgen, the androgen receptor dissociates from HSP and undergoes a conformational change to slow the rate of dissociation from the androgen receptor.The androgen-receptor complex is transported into the nucleus where it binds to DNA and recruits other transcriptional regulators to form a pre-initiation complex and eventually induce expression of specific genes.Testosterone and its active metabolite dihydrotestosterone (DHT) antagonize the androgen receptor to develop masculine sex organs including the prostate, seminal vesicles, penis, and scrotum.,,,,,,,Antagonism of the androgen receptor is also responsible for the development of secondary sexual characteristics including facial and body hair, enlargement of the larynx, thickening of the vocal cords, and changes in muscle and fat distribution.,,,,,,,TargetActionsOrganismAAndrogen receptoragonistHumansUEstrogen receptor alphainhibitorHumansUMineralocorticoid receptorligandHumans",[],"['3-Oxoandrosten (4) Derivatives', 'Anabolic Steroids', 'Androgens', 'Androgens and Estrogens', 'Androstanes', 'Androstenes', 'Androstenols', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OAT3/SLC22A8 Inducers', 'OATP1B3 substrates', 'P-glycoprotein inhibitors', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Testosterone and derivatives', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors']" +DB00794,Primidone,"Primidoneis an antiepileptic used to treat grand mal, psychomotor, and focal epileptic seizures.","['P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P43681', 'P36544', 'P42262', 'Q13002']","Primidone alters sodium and calcium channel transport, reducing the frequency of nerve firing, which may be responsible for its effect on convulsions and essential tremor.4Primidone has a wide therapeutic window as doses of 50-1000mg/day were effective.4Patients should be counselled regarding the risk of status epilepticus with abrupt cessation of primidone.15",CCC1(C(=O)NCNC1=O)C1=CC=CC=C1,"Primidone and its metabolites, phenobarbital and phenylethylmalonamide (PEMA), are active anticonvulsants.Primidone does not directly interact with GABA-A receptors or chloride channels but phenobarbital does.Primidone alters transmembrane sodium and calcium channel transport, reducing the frequency of nerve firing, which may be responsible for the primidone’s effect on convulsions and essential tremor.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGABA(A) Receptorpositive allosteric modulatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumans",[],"['Anti-epileptic Agent', 'Anticholinergic Agents', 'Anticonvulsants', 'Barbiturates', 'Barbiturates and Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inducers (strong)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Enzyme Inducing Antiepileptic Drugs', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Phenobarbital and similars', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones', 'UGT1A1 Inducers']" +DB08895,Tofacitinib,"Tofacitinibis a Janus kinase (JAK) inhibitor used to treat rheumatic conditions, such as rheumatoid arthritis and ankylosing spondylitis, and ulcerative colitis.","['P23458', 'O60674', 'P52333', 'P29597']","Tofacitinib targets inflammation present in rheumatoid arthritis by inhibiting the janus kinases involved in the inflammatory response pathway.In placebo controlled trials of rheumatoid arthritis patients receiving 5mg or 10mg of tofacitinib twice daily, higher ACR20 responses were observed within 2 weeks in some patients (with ACR20 being defined as a minimum 20% reduction in joint pain or tenderness and 20% reduction in arthritis pain, patient disability, inflammatory markers, or global assessments of arthritis by patients or by doctors, according to the American College of Rheumatology (ACR) response criteria list), and improvements in physical functioning greater than placebo were also noted.Common known adverse effects of tofacitinib include headaches, diarrhea, nausea, nasopharyngitis and upper respiratory tract infection. More serious immunologic and hematological adverse effects have also been noted resulting in lymphopenia, neutropenia, anemia, and increased risk of cancer and infection.Before initiations of tofacitinib patients should be tested for latent infections of tuberculosis, and should be closely monitored for signs and symptoms of infection (fungal, viral, bacterial, or mycobacterial) during therapy. Therapy is not to be started in the presence of active infection, systemic or localized, and is to be interrupted if a serious infection occurs.Tofacitinib has been associated with an increased risk of lymphomas, such as Epstein-Barr virus associated lymphomas, and other malignancies (including lung, breast, gastric, and colorectal cancers). It is recommended to monitor lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids.Tofacitinib use is associated with a rapid decrease in C-reactive protein (CRP), dose dependent decreases in natural killer cells, and dose dependent increases in B cells. Depression in C-reactive protein levels continue after 2 weeks of tofacitinib discontinuation and suggest that pharmacodynamic activity last longer than pharmacokinetic half life.",C[C@@H]1CCN(C[C@@H]1N(C)C1=NC=NC2=C1C=CN2)C(=O)CC#N,"Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL, IL, IL, IL, IFN-alpha, and IFN-beta. () Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.Tofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.TargetActionsOrganismATyrosine-protein kinase JAKinhibitorHumansATyrosine-protein kinase JAKantagonistinhibitorHumansATyrosine-protein kinase JAKinhibitorHumansUNon-receptor tyrosine-protein kinase TYKNot AvailableHumans",[],"['Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'Biologics for Rheumatoid Arthritis Treatment', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Disease-modifying Antirheumatic Agents', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Janus Kinase 3, antagonists & inhibitors', 'Janus Kinase Inhibitor', 'Janus Kinase Inhibitors', 'Janus Kinases, antagonists & inhibitors', 'Myelosuppressive Agents', 'Protein Kinase Inhibitors', 'Selective Immunosuppressants']" +DB01200,Bromocriptine,"Bromocriptineis a dopamine D2 receptor agonist used for the treatment of galactorrhea due to hyperprolactinemia and other prolactin-related conditions, as well as in early Parkinsonian Syndrome.","['P14416', 'P35462', 'P28221', 'P08913', 'P08908', 'P18825', 'P18089', 'P41595', 'P21917', 'P28223', 'P28222', 'P28335', 'P21918', 'P21728', 'P35348', 'P35368', 'P25100', 'P34969']","Bromocriptine stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1and D5subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3and D4subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2and D3receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2-receptors. It also exhibits agonist activity (in order of decreasing binding affinity) on 5-hydroxytryptamine (5-HT)1D, dopamine D3, 5-HT1A, 5-HT2A, 5-HT1B, and 5-HT2Creceptors, antagonist activity on α2A-adrenergic, α2C, α2B, and dopamine D1receptors, partial agonist activity at receptor 5-HT2B, and inactivates dopamine D4and 5-HT7receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2Aagonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion making bromocriptine an effective agent for treating disorders associated with hypersecretion of prolactin. Pulmonary fibrosis may be associated bromocriptine’s agonist activity at 5-HT1Band 5-HT2Breceptors.",[H][C@@]12CCCN1C(=O)[C@H](CC(C)C)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=C(Br)NC6=CC=CC(=C56)C4=C3)(O[C@@]21O)C(C)C,"The dopamine Dreceptor is a -transmembrane G-protein coupled receptor associated with Giproteins. In lactotrophs, stimulation of dopamine Dreceptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP-dependent release of Ca+from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p/p MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine Dreceptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansU-hydroxytryptamine receptor DagonistHumansUAlpha-A adrenergic receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansUAlpha-C adrenergic receptoragonistHumansUAlpha-B adrenergic receptoragonistHumansU-hydroxytryptamine receptor BagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor CagonistHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansUAlpha-A adrenergic receptorantagonistagonistHumansUAlpha-B adrenergic receptorantagonistagonistHumansUAlpha-D adrenergic receptoragonistHumansU-hydroxytryptamine receptor antagonistHumans",[],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alkaloids', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Agents (Dopamine Agonist)', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Blood Glucose Lowering Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Ergot-derivative Dopamine Receptor Agonists', 'Ergotamines', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypotensive Agents', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Prolactine Inhibitors', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists']" +DB00381,Amlodipine,Amlodipineis a calcium channel blocker used to treat hypertension and angina.,"['Q13936', 'Q9P0X4', 'Q00975', 'Q02641', 'Q8IZS8', 'P00915', 'P17405', 'A0A024R8I1', 'Q00975']","General pharmacodynamic effectsAmlodipine has a strong affinity for cell membranes, modulating calcium influx by inhibiting selected membrane calcium channels. This drug's unique binding properties allow for its long-acting action and less frequent dosing regimen1,Label.Hemodynamic effectsAfter the administration of therapeutic doses of amlodipine to patients diagnosed with hypertension, amlodipine causes vasodilation, which results in a reduction of supine and standing blood pressure. During these blood pressure reductions, there are no clinically significant changes in heart rate or plasma catecholamine levels with long-term use. Acute intravenous administration of amlodipine reduces arterial blood pressure and increases heart rate in patients with chronic stable angina, however, chronic oral administration of amlodipine in clinical studies did not cause clinically significant alterations in heart rate or blood pressures in patients diagnosed with angina and normal blood pressure. With long-term, once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hoursLabel.Electrophysiologic effectsAmlodipine does not change sinoatrial (SA) nodal function or atrioventricular (AV) conduction in animals or humans. In patients who were diagnosed with chronic stable angina, the intravenous administration of 10 mg of amlodipine did not cause clinically significant alterations A-H and H-V conduction and sinus node recovery time after cardiac pacing. Patients administered amlodipine with concomitant beta-blockers produced similar results. In clinical trials in which amlodipine was given in combination with beta-blockers to patients diagnosed with hypertension or angina, no adverse effects on electrocardiographic parameters were noted. In clinical studies comprised of angina patients alone, amlodipine did not change electrocardiographic intervals or produce high degrees of AV blockLabel.Effects on anginaAmlodipine relieves the symptoms of chest pain associated with angina. In patients diagnosed with angina, daily administration of a single amlodipine dose increases total exercise time, the time to angina onset, and the time to 1 mm ST-segment depression on ECG studies, decreases anginal attack frequency, and decreases the requirement for nitroglycerin tablets9.",CCOC(=O)C1=C(COCCN)NC(C)=C(C1C1=CC=CC=C1Cl)C(=O)OC,"Mechanism of action on blood pressureAmlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to bothdihydropyridineandnondihydropyridinebinding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cellsLabel. Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure.Mechanism of action in anginaThe exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements.Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansUVoltage-dependent N-type calcium channel subunit alpha-BinhibitorHumansUVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansUVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUCarbonic anhydrase inhibitorHumansUSphingomyelin phosphodiesteraseinhibitorHumansUVoltage-dependent N-type calcium channelinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Agents causing hyperkalemia', 'Angiotensin II Antagonists and Calcium Channel Blockers', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Antianginal Agents', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium Channel Blockers and Diuretics', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Pyridines', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00264,Metoprolol,"Metoprololis a beta-blocker used in the treatment of hypertension and angina, and used to reduce mortality due to myocardial infarction.","['P08588', 'P07550', 'P08588', 'P07550', 'P13945']","Administration of metoprolol in normal subjects is widely reported to produce a dose-dependent reduction on heart rate and cardiac output.1This effect is generated due to a decreased cardiac excitability, cardiac output, and myocardial oxygen demand.6In the case of arrhythmias, metoprolol produces its effect by reducing the slope of the pacemaker potential as well as suppressing the rate of atrioventricular conduction.7The Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed a significant improvement in sudden cardiac death and myocardial infarction when patients were given with metoprolol as compared with diuretics. As well, in clinical trials performed in 1990, metoprolol reduces mortality and re-infarction in 17% of the individuals when administered chronically after an episode of myocardial infarction.1",COCCC1=CC=C(OCC(O)CNC(C)C)C=C1,Metoprolol is a beta--adrenergic receptor inhibitor specific to cardiac cells with negligible effect on beta- receptors. This inhibition decreases cardiac output by producing negative chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic sympathomimetics.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansNBeta- adrenergic receptorantagonistHumansUBeta adrenergic receptorinhibitorHumans,[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Beta blocking agents and calcium channel blockers', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Selective', 'Beta Blocking Agents, Selective, and Thiazides', 'Beta-Blockers (Beta1 Selective)', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'OCT2 Inhibitors', 'Photosensitizing Agents', 'Propanolamines']" +DB01119,Diazoxide,Diazoxideis a non diuretic benzothiadiazine indicated for the management of hypoglycemia in patients who produce an excess of insulin caused by a variety of conditions.,"['Q14654', 'P25705', 'P06576', 'P30049', 'P56381', 'P36542', 'P48047']","Diazoxide is a potassium channel activator that enhances cell membrane permeability to potassium ions. By promoting a vasodilatory effect on the smooth muscle in peripheral arterioles, diazoxide lowers blood pressure and peripheral vascular resistance. Diazoxide-induced decreases in blood pressure lead to reflex increases in heart rate and cardiac output.9The oral administration of diazoxide increases blood glucose in a dose-dependent manner. In patients with normal renal function, this effect is observed within an hour and lasts no more than eight hours. The hypotensive effects of diazoxide are usually not detected when administered orally.7Diazoxide administered intravenously may lead to sodium and water retention, severe hypotension, transient myocardial or cerebral ischaemia and gastrointestinal upsets such as nausea, vomiting and abdominal discomfort.9Diazoxide administered orally may cause ketoacidosis and nonketotic hyperosmolar coma, especially in patients with other concurrent conditions.7The use of intravenous or oral diazoxide may lead to the development of pulmonary hypertension in infants and neonates.7,9",CC1=NS(=O)(=O)C2=C(N1)C=CC(Cl)=C2,"Diazoxide is a nondiuretic benzothiadiazine derivative used for the management of symptomatic hypoglycemia. By binding to the sulfonylurea receptor (SUR) subunit of the ATP-sensitive potassium channel (KATP) channel on the membrane of pancreatic beta‐cells, diazoxide promotes a potassium efflux from beta-cells. This hyperpolarizes the cell membrane and prevents the influx of calcium to the pancreatic beta‐cells. Without a sufficient amount of calcium in the cell, insulin release is inhibited.Therefore, the use of diazoxide produces an increase in glucose levels.Diazoxide is chemically related to thiazide diuretics but does not inhibit carbonic anhydrase and does not have chloriuretic or natriuretic activity.It also exhibits hypotensive activity by reducing arteriolar smooth muscle and vascular resistance.The mechanism of action of its hypotensive effect has not been fully elucidated; however, it is possible that it involves the antagonism of calcium.TargetActionsOrganismAATP-sensitive inward rectifier potassium channel inducerHumansUMitochondrial ATP synthase F domaininhibitorHumans",[],"['Antihypertensive Agents', 'Arteriolar Smooth Muscle, Agents Acting On', 'Benzothiadiazines', 'Cardiovascular Agents', 'Direct Vasodilators', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypoglycemia-Treating Agents', 'Hypotensive Agents', 'Potassium Channel Opener', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazide Derivatives', 'Vasodilating Agents']" +DB00594,Amiloride,Amilorideis a pyrizine compound used to treat hypertension and congestive heart failure.,"['P37088', 'P51168', 'P51170', 'P51172', 'P19801', 'Q16515', 'P78348', 'P19634', 'P00749']","Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.",NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N,"Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amiloride exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.TargetActionsOrganismAAmiloride-sensitive sodium channel subunit alphainhibitorHumansAAmiloride-sensitive sodium channel subunit betainhibitorHumansAAmiloride-sensitive sodium channel subunit gammainhibitorHumansAAmiloride-sensitive sodium channel subunit deltainhibitorHumansUAmiloride-sensitive amine oxidase [copper-containing]inhibitorHumansUAcid-sensing ion channel inhibitorHumansUAcid-sensing ion channel inhibitorHumansUSodium/hydrogen exchanger inhibitorHumansUUrokinase-type plasminogen activatorinhibitorHumans",[],"['Acid Sensing Ion Channel Blockers', 'Agents causing hyperkalemia', 'Cardiovascular Agents', 'Decreased Renal K+ Excretion', 'Diuretics', 'Epithelial Sodium Channel Blockers', 'Hypotensive Agents', 'Increased Diuresis', 'Membrane Transport Modulators', 'Natriuretic Agents', 'OCT2 Inhibitors', 'Potassium-Sparing Diuretics', 'Pyrazines', 'Sodium Channel Blockers']" +DB00479,Amikacin,Amikacinis an aminoglycoside used to treat infections caused by more resistant strains of Gram negative bacteria and some Gram positive bacteria.,['P0A7S3'],"Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, however, other antibiotics may be more potent and less toxic to humans.Label,7",NCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O,"The primary mechanism of action of amikacin is the same as that for all aminoglycosides. It binds to bacterial S ribosomal subunits and interferes with mRNA binding and tRNA acceptor sites, interfering with bacterial growth. This leads to disruption of normal protein synthesis and production of non-functional or toxic peptides. Other actions have been postulated for drugs of this class.Label,,Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal against gram-positive and gram-negative bacteria.,TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)",[],"['Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Glycosides', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents']" +DB00314,Capreomycin,Capreomycinis an aminoglycoside antibiotic used as an adjunct drug in tuberculosis.,['P9WJ63'],"Capreomycin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria, including bacteria responsible for causing tuberculosis (TB).",[H][C@@]1(CCN=C(N)N1)[C@]1([H])NC(=O)\C(NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](C)NC(=O)[C@@H](N)CNC1=O)=C/NC(N)=O.[H][C@@]1(CCN=C(N)N1)[C@]1([H])NC(=O)\C(NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CNC1=O)=C/NC(N)=O,"Little is known about capreomycin's exact mechanism of action, but it is thought to inhibit protein synthesis by binding to the S ribosomal unit. Capreomycin also binds to components in the bacterial cell which result in the production of abnormal proteins. These proteins are necessary for the bacteria's survival. Therefore the production of these abnormal proteins is ultimately fatal to the bacteria.TargetActionsOrganismAS/S rRNA (cytidine-'-O)-methyltransferase TlyAinhibitorMycobacterium tuberculosis (strain ATCC / HRv)",[],"['Agents that produce neuromuscular block (indirect)', 'Amino Acids, Peptides, and Proteins', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics, Antitubercular', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inhibitors', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'Peptides', 'Peptides, Cyclic', 'Protein Synthesis Inhibitors']" +DB00864,Tacrolimus,Tacrolimusis a calcineurin inhibitor used to prevent organ transplant rejection and to treat moderate to severe atopic dermatitis.,['P62942'],"Tacrolimus acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Tacrolimus has similar activity to cyclosporine but rates of rejection are lower with tacrolimus. Tacrolimus has also been shown to be effective in the topical treatment of eczema, particularly atopic eczema. It suppresses inflammation in a similar way to steroids, but is not as powerful. An important dermatological advantage of tacrolimus is that it can be used directly on the face; topical steroids cannot be used on the face, as they thin the skin dramatically there. On other parts of the body, topical steroid are generally a better treatment.",CO[C@@H]1C[C@@H](CC[C@H]1O)\C=C(/C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC=C)C(=O)C[C@H](O)[C@H]1C)OC,"The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-. A complex of tacrolimus-FKBP-, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines. Tacrolimus also inhibits the transcription for genes which encode IL-, IL-, IL-, GM-CSF, and TNF-, all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to downregulate the expression of FceRI on Langerhans cells.TargetActionsOrganismAPeptidyl-prolyl cis-trans isomerase FKBPAinhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Agents for Dermatitis, Excluding Corticosteroids', 'Antineoplastic and Immunomodulating Agents', 'Calcineurin Inhibitor Immunosuppressant', 'Calcineurin Inhibitors', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hyperglycemia-Associated Agents', 'Immunologic Factors', 'Immunosuppressive Agents', 'Lactones', 'Misc. Skin and Mucous Membrane Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Polyketides', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00653,Magnesium sulfate,"Magnesium sulfateis a drug used to treat convulsions during pregnancy, nephritis in children, magnesium deficiency, and tetany.","['Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555']","Magnesium sulfate is a small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Magnesium sulfate is gaining popularity as an initial treatment in the management of various dysrhythmias, particularly torsades de pointes, and dyrhythmias secondary to TCA overdose or digitalis toxicity.",[Mg++].[O-]S([O-])(=O)=O,"Magnesium is the second most plentiful cation of the intracellular fluids. It is essential for the activity of many enzyme systems and plays an important role with regard to neurochemical transmission and muscular excitability. Magnesium sulfate reduces striated muscle contractions and blocks peripheral neuromuscular transmission by reducing acetylcholine release at the myoneural junction. Additionally, Magnesium inhibits Ca+influx through dihydropyridine-sensitive, voltage-dependent channels. This accounts for much of its relaxant action on vascular smooth muscle.TargetActionsOrganismAVoltage-dependent L-type calcium channelinhibitorblockerHumans","['Bowel preparation therapy', 'Soaking aid for minor sprains and bruises']","['Agents causing hyperkalemia', 'Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Analgesics', 'Anesthetics', 'Antiarrhythmic agents', 'Anticonvulsants', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dermatologicals', 'Diagnostic Agents', 'Drugs for Constipation', 'Electrolyte Solutions', 'I.V. Solution Additives', 'Laxatives', 'Laxatives, magnesium containing', 'Magnesium Compounds', 'Magnesium Salts', 'Membrane Transport Modulators', 'Metal cations', 'Metal divalent cations', 'Mineral Supplements', 'Miscellaneous Anticonvulsants', 'Osmotic Laxatives', 'Peripheral Nervous System Agents', 'Replacement Preparations', 'Reproductive Control Agents', 'Sensory System Agents', 'Sulfates', 'Sulfur Acids', 'Sulfur Compounds', 'Sulfuric Acids', 'Tests for Bile Duct Patency', 'Tocolytic Agents', 'Vasodilating Agents']" +DB00448,Lansoprazole,"Lansoprazoleis a proton pump inhibitor used to help gastrointestinal ulcers heal, to treat symptoms of gastroesophageal reflux disease (GERD), to eradicate Helicobacter pylori, and to treat hypersecretory conditions such as Zollinger-Ellison Syndrome.","['P20648', 'P10636']","Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells.6Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion.6The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn6Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.76",CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1,"As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated.Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys and Cys, on parietal H+,K+-ATPase resulting in stable disulfides.PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.TargetActionsOrganismAPotassium-transporting ATPase alpha chain inhibitorHumansUMicrotubule-associated protein tauNot AvailableHumans",[],"['Acid Reducers', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'BCRP/ABCG2 Inhibitors', 'Benzimidazoles', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Inhibition Gastric Acid Secretion', 'OAT3/SLC22A8 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Proton Pump Inhibitors', 'Proton-pump Inhibitors', 'Pyridines', 'Sulfoxides', 'Sulfur Compounds']" +DB14500,Potassium,Potassiumis a medication used to treat hypokalemic conditions and to clear the colon prior to colonoscopy.,['P05023'],"Potassium maintains an electrolyte gradient on cell surfaces, keeping at specific concentrations inside and outside of the cell; this impacts fluid and electrolyte balance, nerve transmission, muscle contraction, as well as cardiac and kidney function. Clinical evidence has associated potassium intake with lower blood pressure in adults, reducing the risk stroke and heart disease. Dietary potassium may exert beneficial effects on bone loss in the elderly and kidney stones. Consumption of white vegetables, which are normally high in potassium, is associated with a lower risk of stroke.9A note on gastrointestinal lesionsPotassium in solid oral preparations (for example, tablets) can cause ulcerative or stenotic lesions in the esophagus and stomach. Use diluted liquid potassium preparations or injection preparations if there are concerns about gastrointestinal health.13",[KH],"Potassium ion is the primary intracellular cation found in virtually all body tissues.The total amount of body potassium in adults is estimated at millimole (mmol)/kg body weight (about g for an adult weighing pounds; mmol = milliequivalent or . mg of potassium). Potassium mainly stays in cells, and a small amount can be found in the extracellular fluid. The amount of potassium that stays in the cell (intracellular) is times that of extracellular concentration, creating a transmembrane gradient, regulated by the sodium-potassium (Na+/K+) ATPase transporter. This is an important gradient for nerve conduction, muscle contractions, and renal function.Vomiting, diarrhea, renal disease, medications, and other conditions that alter potassium excretion or shift it inside or outside of cells. In healthy patients individuals with normal renal function, markedly high or low potassium levels are rare.Effect on blood pressurePotassium decreases reduces intravascular volume, by reducing sodium reabsorption through an increase in urinary sodium excretion. This short-term effect, however, does not explain the long-term effects of potassium on blood pressure. Increased plasma potassium levels that occur through intake are associated with vasodilation occurring via stimulation of the sodium-potassium adenosine triphosphatase pump (Na+/-K+ATPase) and opening of potassium channels of the sodium-potassium adenosine triphosphatase pump. Other possible mechanisms of action for potassium may include alterations in barroreflex sensitivity and hormone sensitivity in vascular smooth muscle and cells of the sympathetic nervous system.Effect on electrolyte balance and body systemsThe potassium gradient across the membrane of a cell regulates cell membrane potential, maintained predominantly by the sodium-potassium (Na+/-K+ ATPase pump). Transmembrane electro-chemical gradients encourage diffusion of Na+ extracellularly and K+ intracellularly. Potassium supplementation prevents hypokalemia to maintain this balance and is often used in an oral solution or injection form in the clinical setting, preventing harmful effects such as arrhythmias, abnormal muscle function, and neurological disturbances.When activated, the Na+/-K+ ATPase pump exchanges two extracellular K+ ions for three intracellular sodium (Na+) ions, impacting membrane potential via either excitation or inhibition. This is especially important in the homeostasis of the nervous system, kidney, and cardiac muscle tissue. The body and cell distributions of potassium in normal conditions are known as internal and external balance, respectively.Reduced serum potassium (or imbalance) increases the risk of ventricular arrhythmia, heart failure and left ventricular hypertrophy (LVH).TargetActionsOrganismUSodium/potassium-transporting ATPase subunit alpha-regulatorHumans",[],"['Agents causing hyperkalemia', 'Diuretics', 'Elements', 'High-Ceiling Diuretics', 'Low-Ceiling Diuretics, Excl. Thiazides', 'Metals', 'Metals, Alkali', 'Metals, Light', 'Minerals', 'Potassium Salt', 'Replacement Preparations']" +DB00695,Furosemide,"Furosemideis a loop diuretic used to treat hypertension and edema in congestive heart failure, liver cirrhosis, renal disease, and hypertension.","['Q13621', 'P00918', 'Q9HC97']","Furosemide manages hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide is a potent loop diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption from the proximal and distal tubules, as well as the loop of Henle.9It works directly acts on the cells of the nephron and indirectly modifies the content of the renal filtrate.8Ultimately, furosemide increases the urine output by the kidney. Protein-bound furosemide is delivered to its site of action in the kidneys and secreted via active secretion by nonspecific organic transporters expressed at the luminal site of action.4,9Following oral administration, the onset of the diuretic effect is about 1 and 1.5 hours9, and the peak effect is reached within the first 2 hours.10The duration of effect following oral administration is about 4-6 hours but may last up to 8 hours.12Following intravenous administration, the onset of effect is within 5 minutes, and the peak effect is reached within 30 minutes. The duration of action following intravenous administration is approximately 2 hours. Following intramuscular administration, the onset of action is somewhat delayed.9",NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O,"Furosemide promotes diuresis by blocking tubular reabsorption of sodium and chloride in the proximal and distal tubules, as well as in the thick ascending loop of Henle. This diuretic effect is achieved through the competitive inhibition of sodium-potassium-chloride cotransporters (NKCC) expressed along these tubules in the nephron, preventing the transport of sodium ions from the lumenal side into the basolateral side for reabsorption. This inhibition results in increased excretion of water along with sodium, chloride, magnesium, calcium, hydrogen, and potassium ions.As with other loop diuretics, furosemide decreases the excretion of uric acid.Furosemide exerts direct vasodilatory effects, which results in its therapeutic effectiveness in the treatment of acute pulmonary edema. Vasodilation leads to reduced responsiveness to vasoconstrictors, such as angiotensin II and noradrenaline, and decreased production of endogenous natriuretic hormones with vasoconstricting properties. It also leads to increased production of prostaglandins with vasodilating properties. Furosemide may also open potassium channels in resistance arteries.The main mechanism of action of furosemide is independent of its inhibitory effect on carbonic anhydrase and aldosterone.TargetActionsOrganismASolute carrier family member inhibitorHumansNCarbonic anhydrase inhibitorHumansUG-protein coupled receptor agonistHumans",[],"['Acids, Carbocyclic', 'Amides', 'Amines', 'Aminobenzoates', 'Aniline Compounds', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzene Derivatives', 'Benzoates', 'Cardiovascular Agents', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'High-Ceiling Diuretics', 'High-Ceiling Diuretics and Potassium-Sparing Agents', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis at Loop of Henle', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Nephrotoxic agents', 'Non Potassium Sparing Diuretics', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Ototoxic agents', 'Photosensitizing Agents', 'Sodium Potassium Chloride Symporter Inhibitors', 'Sulfanilamides', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thyroxine-binding globulin substrates', 'UGT1A1 Substrates']" +DB01436,Alfacalcidol,"Alfacalcidolis a vitamin D analogue used for the management of hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in patients with chronic renal failure, as well as some types of rickets and osteomalacia.","['P11473', 'O15528', 'P19793']","Alfacalcidol works to increase serum levels of calcium by stimulating intestinal calcium absorption, reabsorption of calcium from bone, and possibly the renal reabsorption of calcium. It also modestly promotes intestinal phosphorus absorption.9In patients with renal failure, alfacalcidol increased intestinal calcium and phosphorus absorption in a dose-related manner. This increase in calcium and phosphorus levels occurs within three days following drug administration: this effect was reversed within three days of drug discontinuation. In patients with chronic renal failure, serum calcium levels were elevated while parathyroid hormone and alkaline phosphatase levels returned to normal levels within five days following alfacalcidol administration.12Since alfacalcidol suppresses parathyroid hormone, a reduction in parathyroid hormone levels is achieved more rapidly in patients on intermittent intravenous therapy, with significant reductions occurring within three months of therapy. In patients receiving daily oral therapy of alfacalcidol, the time it takes alfacalcidol to normalize plasma calcium levels may be up to several months, possibly reflecting calcium being utilized for bone mineralization.9In patients with nutritional osteomalacia, alfacalcidol increased calcium absorption with six hours of oral administration and the effects peaked at 24 hours.12",CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C,"In conditions like chronic renal failure, renal bone disease, hypoparathyroidism, and vitamin D dependent rickets, the kidneys' capacity for α-hydroxylation is impaired, leading to reduced production of endogenous ,-dihydroxyvitamin D and aberrated mineral metabolism. As an active and potent analog of vitamin D, alfacalcidol works to restore the functions and activities of endogenous ,-dihydroxyvitamin D.TargetActionsOrganismAVitamin D receptoragonistHumansU-hydroxyvitamin D- alpha hydroxylase, mitochondrialNot AvailableHumansURetinoic acid receptor RXR-alphaNot AvailableHumans",[],"['Alimentary Tract and Metabolism', 'Bone Density Conservation Agents', 'Cholestanes', 'Cholestenes', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Fused-Ring Compounds', 'Lipids', 'Membrane Lipids', 'Musculo-Skeletal System', 'Secosteroids', 'Steroids', 'Sterols', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB01223,Aminophylline,"Aminophyllineis a bronchodilator consisting of theophylline that is used for the treatment of bronchospasm due to asthma, emphysema and chronic bronchitis.","['Q14432', 'P30542', 'P0DMS8', 'Q92769']","Aminophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi, produces diuresis, and causes an increase in gastric secretion.",NCCN.CN1C2=C(NC=N2)C(=O)N(C)C1=O.CN1C2=C(NC=N2)C(=O)N(C)C1=O,"Aminophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine AB receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.TargetActionsOrganismAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumansAAdenosine receptor AantagonistHumansAAdenosine receptor AantagonistHumansAHistone deacetylase activatorHumans",[],"['Agents that reduce seizure threshold', 'Amines', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Diamines', 'Drugs for Obstructive Airway Diseases', 'Enzyme Inhibitors', 'Ethylenediamines', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Pharmaceutical Preparations', 'Phosphodiesterase Inhibitors', 'Polyamines', 'Protective Agents', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P1 Receptor Antagonists', 'Purines', 'Purinones', 'Respiratory Smooth Muscle Relaxants', 'Respiratory System Agents', 'Xanthine derivatives', 'Xanthines and Adrenergics']" +DB00201,Caffeine,"Caffeineis a stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. It is also used in to prevent and treat pulmonary complications of premature birth.","['P30542', 'P29274', 'P29275', 'P0DMS8', 'Q01064', 'Q08499', 'Q13370', 'O76074', 'Q07343', 'P21817', 'P54750', 'Q01064', 'Q14123', 'Q9Y233', 'P27815', 'Q07343', 'Q08493', 'Q08499', 'Q9NP56', 'O00408', 'Q14432', 'Q13370', 'O76074', 'P51160', 'Q9HCR9', 'Q13946', 'O60658', 'O95263', 'O76083', 'P16499', 'P35913', 'P78527', 'O00329', 'P42336', 'P42338', 'Q14643', 'Q14571', 'Q14573', 'Q13315']","Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance.1,12,18Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.12",CN1C=NC2=C1C(=O)N(C)C(=O)N2C,"The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows:General and cellular actionsCaffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism.,Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP.This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol.RespiratoryThe exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others.The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm.Central nervous systemCaffeine demonstrates antagonism of all adenosine receptor subtypes (A, Aa, Ab, A) in the central nervous system.,Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the Aa receptor.Renal systemCaffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion.Cardiovascular systemAdenosine receptor antagonism at the A receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by to mmHg when it is not taken regularly, versus no effect in those who consume it regularly.The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain.,TargetActionsOrganismAAdenosine receptor AantagonistHumansAAdenosine receptor AaantagonistHumansAAdenosine receptor AbantagonistHumansAAdenosine receptor AantagonistHumansAPhosphodiesterase enzymesinhibitorHumansUcAMP-specific ','-cyclic phosphodiesterase BinhibitorHumansURyanodine receptor Not AvailableHumansUCyclic nucleotide phosphodiesteraseinhibitorHumansUDNA-dependent protein kinase catalytic subunitinhibitorHumansUPhosphatidylinositol ,-bisphosphate -kinase catalytic subunit delta isoforminhibitorHumansUPhosphatidylinositol ,-bisphosphate -kinase catalytic subunit alpha isoforminhibitorHumansUPhosphatidylinositol ,-bisphosphate -kinase catalytic subunit beta isoforminhibitorHumansUInositol ,,-trisphosphate receptorinhibitorHumansUSerine-protein kinase ATMinhibitorHumans","['Analgesia', 'Antacid therapy', 'Athletic Performance']","['Alkaloids', 'Anorexigenic Agents & Respiratory and CNS Stimulants', 'BCRP/ABCG2 Inhibitors', 'Caffeine and Caffeine Containing Products', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Diagnostic Agents', 'Drugs for Obstructive Airway Diseases', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Phosphodiesterase Inhibitors', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Purinergic Agents', 'Purinergic Antagonists', 'Purines', 'Purinones', 'Respiratory and CNS Stimulants', 'Tests for Gastric Secretion', 'Tricarboxylic Acids', 'Xanthine derivatives']" +DB00755,Tretinoin,"Tretinoinis a vitamin A derivative used to treat acne vulgaris and certain types of promyelocytic leukemia, as well as various skin conditions in over-the-counter medications.","['P10276', 'P10826', 'P13631', 'P19793', 'P28702', 'P48443', 'P29762', 'P49788', 'P00352', 'O94788', 'Q8NFJ5', 'P31025', 'Q9NY56', 'P02753', 'Q16654', 'Q14081']","Tretinoin is a vitamin A derivative that promotes cell production, proliferation, and differentiation. When used topically, tretinoin regulates epidermal cell turnover and collagen production. It also prevents collagen loss, reduces inflammation, and blocks the induction of matrix metalloproteinase (MMP), which are enzymes that disrupt collagen and elastic fibres.1,2,3,10In short-term and long-term studies, topical application of tretinoin at doses ranging from 0.001% to 0.1% was associated with improvements in clinical signs of photoaging and fine wrinkles, increased epidermal thickness, compaction of the stratum corneum, and decreased melanin content.4,10,11,7It also improved melanocyte differentiation and distribution, promotion of epidermal hyperplasia, and angiogenesis.7Tretinoin exhibits antineoplastic activities when given orally.13Tretinoin was shown to induce differentiation in tumour cells.6It induced cytodifferentiation and decreased acute promyelocytic leukemia (APL) cell proliferation in culture andin vivo. In patients with APL, tretinoin promoted the initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission.13",C\C(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C/C(O)=O,"The exact mechanism of action of tretinoin in skin conditions and acute promyelocytic leukemia (APL) has not been fully elucidated; however, several proposed mechanisms exist. Tretinoin is believed to exert its pharmacological actions by binding to and activating two types of nuclear receptors - retinoic acid receptors (RARs) alpha, beta, and gamma and retinoid X receptors (RXRs). In the human skin, RARs (especially RAR-alpha) form heterodimers with RXR to act as inducible transcription regulators of genes involved in cell differentiation by binding to retinoic acid response elements.,Tretinoin binds to RXRs to promote epidermal proliferation. It also blocks the actions of inflammatory mediators, enhancing procollagen production and collagen type I and III formations.,,,Some animal and human studies suggest that tretinoin induces the expression of transforming growth factor beta (TGF-β), which stimulates the transcription of several types of collagen messenger RNA. Collagen formation curtails further solar UV-induced skin damage and aging processes.Acne is associated with abnormal follicular formation from excessive keratinization of epithelial cells. Tretinoin promotes cornified cell detachment and enhances keratinocyte shedding. It also stimulates mitotic activity and loosely-adherent corneocyte turnover to expel comedo contents, reducing microcomedo precursor lesions of acne vulgaris.,Tretinoin may reduce epidermal melanin and pigmentation by increasing keratinocyte turnover and reducing tyrosinase activity.,RAR-alpha and -beta have also been implicated in APL.APL is characterized by a t(;) chromosomal translocation, which fuses the promyelocytic myeloid leukemia (PML) gene with the RAR-alpha gene.,The resulting PML-RAR-alpha fusion protein plays a role in the pathogenesis of APL by aberrating promyelocyte differentiation. The PML-RAR-alpha fusion protein is found to be predominant in leukemic cells, exerting a dominant negative effect on RAR, RXR and PML function.Tretinoin induces terminal differentiation in hemopoietic precursor cell lines and APL cells.Tretinoin is believed to promote caspase-mediated cleavage and proteasome-dependent degradation to cause apoptosis and degradation of the PML-RAR-alpha fusion protein.It may also convert the fusion protein from a transcription repressor to an activator.TargetActionsOrganismARetinoic acid receptor alphaagonistHumansARetinoic acid receptor betaagonistHumansARetinoic acid receptor gammaagonistHumansURetinoic acid receptor RXR-alphaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor RXR-gammaagonistHumansUCellular retinoic acid-binding protein binderHumansURetinoic acid receptor responder protein agonistHumansURetinal dehydrogenase substrateHumansURetinal dehydrogenase substrateHumansURetinoic acid-induced protein regulatorHumansULipocalin-binderHumansUOdorant-binding protein abinderHumansURetinol-binding protein binderHumansU[Pyruvate dehydrogenase [lipoamide]] kinase isozyme , mitochondrialupregulatorHumansUCarcinoembryonic antigendownregulatorHumans",[],"['Agents that produce hypertension', 'Alkenes', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Biological Factors', 'Cardiotoxic antineoplastic agents', 'Carotenoids', 'Cell Stimulants and Proliferants', 'Cyclohexanes', 'Cyclohexenes', 'Cycloparaffins', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Diterpenes', 'Hydrocarbons, Acyclic', 'Hypotensive Agents', 'Immunosuppressive Agents', 'Keratolytic Agents', 'Pigments, Biological', 'Polyenes', 'Retinoids', 'Retinoids for cancer treatment', 'Retinoids for Topical Use in Acne', 'Terpenes', 'UGT2B7 substrates', 'Vitamin A', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00675,Tamoxifen,"Tamoxifenis a selective estrogen receptor modulator used to treat estrogen receptor positive breast cancer, reduce the risk of invasive breast cancer following surgery, or reduce the risk of breast cancer in high risk women.","['P03372', 'Q92731', 'P17252', 'P05771', 'Q05655', 'Q02156', 'P05129', 'P41743', 'Q04759', 'Q05513', 'P04278', 'Q15125', 'P10275', 'Q12809', 'O75469', 'P62508', 'P45983']","Tamoxifen is a selective estrogen receptor modulator that inhibits growth and promotes apoptosis in estrogen receptor positive tumors.1,8It has a long duration of action as the active metabolite N-desmethyltamoxifen has a half life of approximately 2 weeks.15,16It has a narrow therapeutic index as higher doses can lead to breathing difficulty or convulsions.15,16Tamoxifen administration is also associated with an increased incidence of uterine malignancies.15,16",CC\C(=C(/C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1,"Tamoxifen competitively inhibits estrogen binding to its receptor, which is critical for it's activity in breast cancer cells.Tamoxifen leads to a decrease in tumor growth factor α and insulin-like growth factor , and an increase in sex hormone binding globulin.The increase in sex hormon binding globulin limits the amount of freely available estradiol.These changes reduce levels of factors that stimulate tumor growth.Tamoxifen has also been shown to induce apoptosis in estrogen receptor positive cells.This action is thought to be the result of inhibition of protein kinase C, which prevents DNA synthesis.Alternate theories for the apoptotic effect of tamoxifen comes from the approximately fold increase in intracellular and mitochondrial calcium ion levels after administration or the induction of tumor growth factor β.TargetActionsOrganismAEstrogen receptor alphaantagonistagonistHumansAEstrogen receptor betaantagonistagonistHumansAProtein kinase CinhibitorHumansASex hormone-binding globulininducerHumansU-beta-hydroxysteroid-Delta(),Delta()-isomeraseinhibitorHumansUAndrogen receptorNot AvailableHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUNuclear receptor subfamily group I member Not AvailableHumansUEstrogen-related receptor gammaNot AvailableHumansUMitogen-activated protein kinase modulatorHumans",['Ovulation induction therapy'],"['Anti-Estrogens', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'Benzylidene Compounds', 'BSEP/ABCB11 Inhibitors', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Estrogen Agonist/Antagonist', 'Estrogen Antagonists', 'Estrogen Receptor Modulators', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Selective Estrogen Receptor Modulators', 'Stilbenes', 'Thyroxine-binding globulin inducers', 'UGT2B17 substrates', 'UGT2B7 substrates', 'UGT2B7 Substrates with a Narrow Therapeutic Index']" +DB00973,Ezetimibe,"Ezetimibeis a cholesterol absorption inhibitor used to lower total cholesterol, LDL-C, Apo-B, and non-HDL-C in primary hyperlipidemia and familial cholesterolemia.","['Q9UHC9', 'P35610', 'P15144']","Ezetimibe was shown to reduce the levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), and increase high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia.5This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone.5In clinical trials involving patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia, a recommended therapeutic dose of ezetimibe was effective in reducing the LDL levels by 15-20% while increasing HDL-C by 2.5-5%.4The effects of increased exposure to ezetimibe secondary to moderate-severe hepatic impairment have not been assessed - patients meeting these criteria should avoid the use of ezetimibe.5Post-marketing reports indicate the potential for myopathy and rhabdomyolysis in patients taking ezetimibe, and this risk appears to be exacerbated in patients concurrently receiving, or having recently received, statin therapy.5",[H][C@]1(CC[C@H](O)C2=CC=C(F)C=C2)C(=O)N(C2=CC=C(F)C=C2)[C@]1([H])C1=CC=C(O)C=C1,"Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients.The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C-Like (NPCL) protein. NPCL is expressed on enterocytes/gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein (AP) complex and clathrin.Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it binds to the sterol-sensing domain of NPCL and forms a NPCL/cholesterol complex. The complex is then internalized or endocytosed by joining to AP clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment.Ezetimibe does not require exocrine pancreatic function for its pharmacological activity; rather, it localizes and appears to act at the brush border of the small intestine. Ezetimibe selectively blocks the NPCL protein in the jejunal brush border, reducing the uptake of intestinal lumen micelles into the enterocyte.Overall, ezetimibe causes a decrease in the delivery of intestinal cholesterol to the liver and reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. While the full mechanism of action of ezetimibe in reducing the entry of cholesterol into both enterocytes and hepatocytes is not fully understood, one study proposed that ezetimibe prevents the NPCL/sterol complex from interacting with AP in clathrin coated vesicles and induces a conformational change in NPCL, rendering it incapable of binding to sterols.Another study suggested that ezetimibe disrupts the function of other protein complexes involved in regulating cholesterol uptake, including the CAV–annexin heterocomplex.TargetActionsOrganismANiemann-Pick C-like protein inhibitorHumansASterol O-acyltransferase inhibitorHumansUAminopeptidase NotherHumans",[],"['Anticholesteremic Agents', 'Azetines', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Decreased Cholesterol Absorption', 'Dietary Cholesterol Absorption Inhibitor', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein substrates', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB00202,Succinylcholine,"Succinylcholineis a depolarizing skeletal muscle relaxant used adjunctly to anesthesia and for skeletal muscle relaxation during intubation, mechanical ventilation, and surgical procedures.","['Q9GZZ6', 'Q15822', 'P32297', 'P43681', 'P30532', 'Q15825', 'P36544', 'Q9UGM1', 'P17787', 'Q05901', 'P30926', 'P08172', 'P20309']","Succinylcholine's neuromuscular blockade takes effect within 60 seconds of intravenous administration and lasts between four to six minutes.2Similar to acetylcholine, it binds to cholinergic receptors of the motor endplate to induce membrane depolarization and, eventually, muscle paralysis, which may be maintained for as long as an adequate concentration of succinylcholine remains at the receptor site.8Succinylcholine has no direct action on smooth or cardiac muscle, nor does it appear to act on pre-synaptic or ganglionic acetylcholine receptors.5The paralysis induced by succinylcholine has been described as ""progressive"", first involving the muscles of the face and glottis, then the intercostals and diaphragm, then followed by other skeletal muscles.8Succinylcholine has no effect on consciousness or pain threshold, and must therefore be used in conjunction with adequate anesthesia.9There have been rare reports of the development of acute rhabdomyolysis with hyperkalemia - resulting in ventricular dysrhythmias, cardiac arrest, and death - after the intravenous administration of succinylcholine to apparently healthy pediatric patients who were subsequently found to have undiagnosed skeletal myopathy (most frequently Duchenne's muscular dystrophy).9Infants or children experiencing seemingly idiopathic cardiac arrest soon after the administration of succinylcholine should therefore be treated immediately for hyperkalemia. Given that patients may not present with any apparent risk factors, the use of succinylcholine in pediatric patients should be restricted to emergency intubation or other situations in which a suitable alternative is unavailable.9",C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C,"Succinylcholine is a depolarizing neuromuscular blocker, meaning it causes a prolonged period of membrane depolarization in order to exert its therapeutic effects. It binds to the post-synaptic cholinergic receptors found on motor endplates, thereby inducing first transient fasciculations followed by skeletal muscle paralysis.TargetActionsOrganismANeuronal Acetylcholine (nACh) Receptor SubunitsagonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumans",['Tracheal Intubation'],"['Acids, Acyclic', 'Agents causing hyperkalemia', 'Amines', 'Ammonium Compounds', 'Central Nervous System Depressants', 'Choline Derivatives', 'Cholinesterase substrates', 'Dicarboxylic Acids', 'Ethanolamines', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular Depolarizing Agents', 'Neuromuscular Depolarizing Blockade', 'Neurotoxic agents', 'Nitrogen Compounds', 'Onium Compounds', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds', 'Succinates', 'Trimethyl Ammonium Compounds']" +DB01226,Mivacurium,Mivacuriumis a short-acting non-depolarizing neuromuscular blocking agent used to induce anesthesia during intubation and promote skeletal muscle relaxation during surgery or mechanical ventilation.,"['Q15822', 'P08172', 'P20309', 'P06276']","Mivacurium is a short-acting, nondepolarizing skeletal neuromuscular blocking agent which is hydrolyzed by plasma cholinesterase. Mivacurium results in a blockade of neuromuscular transmission by binding competitively with cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine. The neuromuscular block produced by mivacurium is readily antagonized by anticholinesterase agents. The deeper the level of neuromuscular block at reversal, the longer the time required for recovery of neuromuscular function and the greater the dose of anticholinesterase agent required. Because spontaneous recovery after mivacurium is rapid, routine reversal may not always result in a clinical benefit.",COC1=CC(C[C@@H]2C3=CC(OC)=C(OC)C=C3CC[N+]2(C)CCCOC(=O)CC\C=C\CCC(=O)OCCC[N+]2(C)CCC3=CC(OC)=C(OC)C=C3[C@H]2CC2=CC(OC)=C(OC)C(OC)=C2)=CC(OC)=C1OC,"Mivacurium binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in a block of neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumansNMuscarinic acetylcholine receptor Mantagonistpartial agonistHumansNMuscarinic acetylcholine receptor MantagonistHumansUCholinesteraseNot AvailableHumans","['Curarization therapy', 'General Anesthesia', 'Neuromuscular blocking therapy', 'Facilitation of small bowel intubation therapy', 'Smooth muscle relaxation prior to radiological procedures therapy']","['Agents producing tachycardia', 'Anticholinergic Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Cholinesterase substrates', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Muscarinic Antagonists', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Nicotinic Antagonists', 'Peripheral Nervous System Agents']" +DB01011,Metyrapone,Metyraponeis a steroid 11-beta-monooxygenase inhibitor used to test hypothalamic-pituitary ACTH function.,"['P15538', 'P00183']",Metopirone is an inhibitor of endogenous adrenal corticosteroid synthesis.,CC(C)(C(=O)C1=CN=CC=C1)C1=CC=CN=C1,"The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the -ß-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary. With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, -desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine. These metabolites are readily determined by measuring urinary -hydroxycorticosteroids (-OHCS) or -ketogenic steroids (-KGS). Because of these actions, metopirone is used as a diagnostic test, with urinary -OHCS measured as an index of pituitary ACTH responsiveness. Metopirone may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.TargetActionsOrganismACytochrome P B, mitochondrialinhibitorHumansUCamphor -monooxygenaseother/unknownPseudomonas putida",[],"['Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Diagnostic Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Noxae', 'Pyridines', 'Steroid Synthesis Inhibitors', 'Tests for Pituitary Function', 'Toxic Actions']" +DB00741,Hydrocortisone,"Hydrocortisoneis a glucocorticoid used to treat corticosteroid-responsive dermatoses, endocrine disorders, immune conditions, and allergic disorders.","['P04150', 'P04083']","Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes.10Hydrocortisone has a wide therapeutic index8and a moderate duration of action.1,6Patients should stop taking the medication if irritation or sensitization occurs.14,15,16,17,18,19",[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumansAAnnexin AagonistHumans",['Palliative Treatment'],"['11-Hydroxycorticosteroids', '17-Hydroxycorticosteroids', 'Adrenal Cortex Hormones', 'Adrenals', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Alimentary Tract and Metabolism', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids Acting Locally', 'Corticosteroids for Local Oral Treatment', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Weak (Group I)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydrocortisone and derivatives', 'Hydroxycorticosteroids', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'Nasal Preparations', 'OAT3/SLC22A8 Substrates', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Otologicals', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Sensory Organs', 'Steroids', 'Stomatological Preparations', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Vasoprotectives']" +DB00495,Zidovudine,Zidovudineis a dideoxynucleoside used in the treatment of HIV infection.,"['Q72547', 'O14746']","Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.",CC1=CN([C@H]2C[C@H](N=[N+]=[N-])[C@@H](CO)O2)C(=O)NC1=O,"Zidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active ′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). It inhibits the activity of HIV- reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus UTelomerase reverse transcriptaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Deoxyribonucleosides', 'Dideoxynucleosides', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'P-glycoprotein substrates', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Reverse Transcriptase Inhibitors', 'Toxic Actions', 'UGT1A1 Inducers', 'UGT1A1 Substrates', 'UGT2B7 substrates']" +DB01219,Dantrolene,Dantroleneis a direct-acting skeletal muscle relaxant used for the treatment of management of the fulminant hypermetabolism of skeletal muscle leading to malignant hyperthermia crisis.,['P21817'],"Dantrolene is classified as a direct-acting skeletal muscle relaxant. It is currently the only specific and effective treatment for malignant hyperthermia. In isolated nerve-muscle preparation, Dantrium has been shown to produce relaxation by affecting the contractile response of the muscle at a site beyond the myoneural junction. In skeletal muscle, Dantrium dissociates excitation-contraction coupling, probably by interfering with the release of Ca2+from the sarcoplasmic reticulum. In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In selected humans, it has been postulated that “triggering agents” (e.g.,general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. This elevated myoplasmic calcium activates acute cellular catabolic processes that cascade to the malignant hyperthermia crisis. It is hypothesized that addition of Dantrium to the “triggered” malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm.",[O-][N+](=O)C1=CC=C(C=C1)C1=CC=C(O1)\C=N\N1CC(=O)NC1=O,"Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor , and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction.TargetActionsOrganismARyanodine receptor antagonistHumans",[],"['Agents causing hyperkalemia', 'Agents that produce neuromuscular block (indirect)', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dantrolene and Derivatives', 'Decreased Striated Muscle Contraction', 'Decreased Striated Muscle Tone', 'Direct-acting Skeletal Muscle Relaxants', 'Hepatotoxic Agents', 'Hydantoins', 'Imidazoles', 'Imidazolidines', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Peripheral Nervous System Agents', 'Thyroxine-binding globulin substrates']" +DB01235,Levodopa,"Levodopais a dopamine precursor used in the management of Parkinson's disease, often in combination with carbidopa, as well as other conditions associated with parkinsonism.","['P21728', 'P21918', 'P14416', 'P35462', 'P21917']","Levodopa is able to cross the blood-brain barrier while dopamine is notLabel,8. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrierLabel,8. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylaseLabel,8.",N[C@@H](CC1=CC(O)=C(O)C=C1)C(O)=O,"Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamineLabel,. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptorsLabel,.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumans",[],"['Amines', 'Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Agents (Dopamine Agonist)', 'Anti-Parkinson Drugs', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Catecholamines', 'Catechols', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dihydroxyphenylalanine', 'Dopa and Dopa Derivatives', 'Dopamine Agents', 'Hypotensive Agents', 'Levodopa, antagonists & inhibitors', 'Nervous System', 'Neurotransmitter Agents', 'Phenols', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00591,Fluocinolone acetonide,"Fluocinolone acetonideis a corticosteroid used to treat skin conditions, eczematous otitis externa, diabetic macular edema, and non-infectious uveitis of the posterior segment of the eye.","['P04150', 'P04083', 'P07355', 'P12429', 'P09525', 'P08758', 'P04054']","Fluocinolone acetonide is a synthetic anti-inflammatory corticosteroid and thus, the effect of its interaction with the body produces vasoconstriction and suppression of membrane permeability, mitotic activity, immune response and release of inflammatory mediators.18For its ophthalmic indications, fluocinolone acetonide is administered as intravitreal micro-insert. This preparation was observed in clinical trials to reduce the recurrence of uveitis flares by 2 fold when compared with the non treated patients even after six months after initial administration. As well the intraocular pressure seemed to increase slightly with the presence of the fluocinolone implant but it is important to monitor intraocular pressure.15",[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)CO,"Fluocinolone acetonide is a corticosteroid and thus, it can be inferred that it acts by inhibiting the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, collagen deposition, and scar formation.Some reports have indicated that fluocinolone acetonide presents a high binding affinity for the glucocorticoid receptor. After binding the receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements in the promoter region of the target genes.This effect promotes the induction of phospholipase A inhibitory proteins (lipocortins). Through this mechanism of action, it is thought that fluocinolone induces mainly one of the lipocortins, annexin , which will later mediate the synthesis of inflammatory mediators such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid which is the precursor of all these inflammatory mediators. Hence, the induction of these proteins will prevent the release of arachidonic acid by phospholipase A.TargetActionsOrganismAGlucocorticoid receptoragonistHumansAAnnexin AinducerHumansAAnnexin AinducerHumansAAnnexin AinducerHumansAAnnexin AinducerHumansAAnnexin AinducerHumansUPhospholipase AinhibitorHumans","['Postoperative Care', 'Perioperative management therapy', 'Postoperative treatment']","['Adrenal Cortex Hormones', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Ophthalmologicals', 'Otologicals', 'Pregnadienes', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated', 'Vasoprotectives']" +DB00121,Biotin,Biotinis a B-complex vitamin found in many multivitamin products.,"['P05166', 'P50747', 'Q9HCC0', 'O00763', 'Q96RQ3', 'P11498', 'P05165', 'Q13085']","Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or ""cradle cap"". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes.",[H][C@]12CS[C@@H](CCCCC(O)=O)[C@@]1([H])NC(=O)N2,"Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids.TargetActionsOrganismUPropionyl-CoA carboxylase beta chain, mitochondrialcofactorHumansUBiotin--protein ligasesubstrateHumansUMethylcrotonoyl-CoA carboxylase beta chain, mitochondrialcofactorHumansUAcetyl-CoA carboxylase cofactorHumansUMethylcrotonoyl-CoA carboxylase subunit alpha, mitochondrialcofactorHumansUPyruvate carboxylase, mitochondrialcofactorHumansUPropionyl-CoA carboxylase alpha chain, mitochondrialcofactorHumansUAcetyl-CoA carboxylase cofactorHumans",['Nutritional supplementation'],"['Alimentary Tract and Metabolism', 'Coenzymes', 'Diet, Food, and Nutrition', 'Dietary Supplements', 'Enzymes and Coenzymes', 'Food', 'Growth Substances', 'Imidazoles', 'Micronutrients', 'Physiological Phenomena', 'Supplements', 'Vitamin B Complex', 'Vitamins']" +DB00153,Ergocalciferol,Ergocalciferolis a vitamin found in many supplement products.,"['P11473', 'Q06432', 'Q9Y698', 'O60359', 'Q9UBN1', 'Q9UF02', 'Q9BXT2', 'P62955', 'Q8WXS5', 'P54289', 'Q9NY47', 'Q8IZS8', 'Q7Z3S7', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'Q00975', 'O00555', 'Q15878', 'O43497', 'O95180', 'Q9P0X4']","After the activation of the vitamin D receptor, some of the biological changes produced by ergocalciferol include mobilization and accretion of calcium and phosphorus in the bone, absorption of calcium and phosphorus in the intestine, and reabsorption of calcium and phosphorus in the kidney.7Some other effects known to be produced due to the presence of vitamin D are osteoblast formation, fetus development, induction of pancreatic function, induction of neural function, improvement of immune function, cellular growth and cellular differentiation.7When compared to its vitamin D counterpartcholecalciferol, ergocalciferol has been shown to present a reduced induction of calcidiol and hence, it is less potent.2Ergocalciferol supplementation in patients with end-stage renal disease has been shown to generate a significant benefit in lab parameters of bone and mineral metabolism as well as improvement in glycemic control, serum albumin levels and reduced levels of inflammatory markers.1",CC(C)[C@@H](C)\C=C\[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C,"For its activity, ergocalciferol is required to be transformed to its major active circulating hydroxylated metabolite and transported to the target organs in order to bind to its target, the vitamin D receptor.The activation of the vitamin D receptor is part of the vitamin D endocrine system and it is described by the production of a change in the transcription rates of the vitamin D receptor target genes.The target genes in the DNA affected by the presence of ergocalciferol are called vitamin D response elements which are dependent on co-modulators.The vitamin D receptor is a transcription factor and member of the steroid hormone nuclear receptor family. It presents a DNA binding domain (VDRE) that, when activated, recruits coregulatory complexes to regulate the genomic activity.Additionally, ergocalciferol presents nongenomic effects such as the stimulation of intestinal calcium transport via transcaltachia.TargetActionsOrganismAVitamin D receptoragonistHumansNVoltage-dependent calcium channelinducerHumans",['Dietary supplementation'],"['Alimentary Tract and Metabolism', 'Bone Density Conservation Agents', 'Calcium-Regulating Hormones and Agents', 'Diet, Food, and Nutrition', 'Food', 'Fused-Ring Compounds', 'Growth Substances', 'Lipids', 'Micronutrients', 'Physiological Phenomena', 'Secosteroids', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00829,Diazepam,"Diazepamis a long-acting benzodiazepine with rapid onset commonly used to treat panic disorders, severe anxiety, alcohol withdrawal, and seizures.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle- relaxant, anticonvulsant and amnestic effects15,16,6. Most of these effects are thought to result from facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system15,16,6.",CN1C2=C(C=C(Cl)C=C2)C(=NCC1=O)C1=CC=CC=C1,"Diazepam is a benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties,,.Benzodiazepines, such as diazepam, bind to receptors in various regions of the brain and spinal cord. This binding increases the inhibitory effects of gamma-aminobutyric acid (GABA),,. GABAs functions include CNS involvement in sleep induction. Also involved in the control of hypnosis, memory, anxiety, epilepsy and neuronal excitability,,.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans","['Sedation', 'Perioperative management therapy']","['Adjuvants, Anesthesia', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Anti-Anxiety Agents', 'Anticonvulsants', 'Autonomic Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00428,Streptozocin,Streptozocinis a nitrosourea antineoplastic agent used in the treatment of metastatic pancreatic islet cell carcinoma.,"['Q89ZI2', 'P11168', 'O60502']","Streptozocin is an antitumour antibiotic consisting of a nitrosourea moiety interposed between a methyl group and a glucosamine. Streptozocin is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects.",CN(N=O)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O,"Although its mechanism of action is not completely clear, streptozocin is known to inhibit DNA synthesis, interfere with biochemical reactions of NAD and NADH, and inhibit some enzymes involved in gluconeogenesis. Its activity appears to occur as a result of formation of methylcarbonium ions, which alkylate or bind with many intracellular molecular structures including nucleic acids. Its cytotoxic action is probably due to cross-linking of strands of DNA, resulting in inhibition of DNA synthesis.TargetActionsOrganismAO-GlcNAcase BT_antagonistBacteroides thetaiotaomicron (strain ATCC / DSM / NCTC / E / VPI-)ADNAcross-linking/alkylationHumansUSolute carrier family , facilitated glucose transporter member ligandHumansUBifunctional protein NCOATNot AvailableHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Amides', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nitroso Compounds', 'Nitrosourea Compounds', 'Nitrosoureas', 'P-glycoprotein inducers']" +DB01229,Paclitaxel,"Paclitaxelis a taxoid chemotherapeutic agent used as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast and lung cancer.","['Q9H4B7', 'P10415', 'P27816', 'P11137', 'P10636', 'O75469']","Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or ""bundles"" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.",[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C,"Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the ""building block"" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl- (B-cell leukemia ) and thus arresting its function.TargetActionsOrganismATubulin beta- chaininhibitorHumansAApoptosis regulator Bcl-inhibitorHumansAMicrotubule-associated protein Not AvailableHumansAMicrotubule-associated protein Not AvailableHumansAMicrotubule-associated protein tauNot AvailableHumansUNuclear receptor subfamily group I member inducerHumans",[],"['Agents Causing Muscle Toxicity', 'Albumins', 'Amino Acids, Peptides, and Proteins', 'Antimitotic Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Cardiotoxic antineoplastic agents', 'Cyclodecanes', 'Cycloparaffins', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Diterpenes', 'Hypotensive Agents', 'Immunosuppressive Agents', 'Microtubule Inhibition', 'Microtubule Inhibitors', 'Mitosis Modulators', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Neurotoxic agents', 'OATP1B3 substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Proteins', 'Taxane Derivatives', 'Taxoids', 'Terpenes', 'Tubulin Modulators']" +DB00290,Bleomycin,"Bleomycinis a chemotherapy agent used to treat various malignancies, including head and neck malignancy, lymphoma, and testicular tumors, among others.","['P18858', 'P49916']","Bleomycin is an antibiotic which has been shown to have antitumor activity. Bleomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Bleomycin has been shownin vitroto inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. The antibiotic antitumor drugs are cell cycle-nonspecific except for Bleomycin (which has major effects in G2 and M phases).",[H][C@](C)(NC(=O)[C@@]([H])(NC(=O)C1=NC(=NC(N)=C1C)[C@H](CC(N)=O)NC[C@H](N)C(N)=O)[C@@]([H])(OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(OC(N)=O)C1O)C1=CNC=N1)[C@@H](O)[C@H](C)C(=O)N[C@]([H])(C(=O)NCCC1=NC(=CS1)C1=NC(=CS1)C(=O)NCCC[S+](C)C)[C@@]([H])(C)O,"Although the exact mechanism of action of bleomycin is unknown, available evidence would seem to indicate that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis. As evident inin vitrostudies, the DNA-cleaving actions of bleomycin is dependent on oxygen and metal ions. It is believed that bleomycin chelates metal ions (primarily iron) producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA.TargetActionsOrganismADNAcleavageHumansUDNA ligase inhibitorHumansUDNA ligase inhibitorHumans",['Palliative Treatment'],"['Amino Acids, Peptides, and Proteins', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cardiotoxic antineoplastic agents', 'Cytoprotective Agent', 'Cytotoxic Antibiotics and Related Substances', 'Drugs that are Mainly Renally Excreted', 'Glycoconjugates', 'Glycopeptides', 'Immunosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Peptides']" +DB00773,Etoposide,Etoposideis a podophyllotoxin derivative used to treat testicular and small cell lung tumors.,"['P11388', 'Q02880']","Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.",[H][C@]12COC(=O)[C@]1([H])[C@H](C1=CC(OC)=C(O)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@H]2O[C@@H]1O[C@]2([H])CO[C@@H](C)O[C@@]2([H])[C@H](O)[C@H]1O,"Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect.TargetActionsOrganismADNA topoisomerase -alphainhibitorHumansNDNA topoisomerase -betainhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Carbohydrates', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Glucosides', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Naphthalenes', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Podophyllotoxin', 'Podophyllotoxin Derivatives', 'Tetrahydronaphthalenes', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index']" +DB00157,NADH,NADHis a nutrient used in some supplement products.,"['O60701', 'P07327', 'Q00796', 'P08319', 'P00326', 'P00325', 'P40394', 'P21695', 'Q6ZMR3', 'P11766', 'P15121', 'Q99714', 'P40926', 'P00338', 'P23368', 'P51659', 'Q9BYZ2', 'P07864', 'P07195', 'Q08426', 'Q16836', 'Q16798', 'Q02338', 'P40925', 'P31937', 'P37058', 'P04035', 'P48163', 'O43175', 'P56937', 'P51553', 'O43837', 'P50213', 'P14061', 'P37059', 'Q92781', 'O95479', 'Q92506', 'P17516', 'P12268', 'P42330', 'P15428', 'Q13630', 'Q04828', 'P28845', 'P26439', 'P14060', 'P20839', 'P40939', 'P05091', 'P80365', 'P52895', 'Q15738', 'P48448', 'Q02252', 'P30838', 'P00352', 'O14556', 'P49189', 'P47895', 'P30837', 'P43353', 'P04406', 'O94788', 'P51648', 'P51649', 'P49419', 'P30043', 'Q96C36', 'P32322', 'P00367', 'P11177', 'P29803', 'P08559', 'P53004', 'P16219', 'P00374', 'Q02218', 'P49448', 'Q9UBM7', 'P16083', 'P03891', 'Q9UDR5', 'P03897', 'O75251', 'P11586', 'P13995', 'P30038', 'P00387', 'Q86Y39', 'P03905', 'P09417', 'P03886', 'Q13423', 'Q16718', 'Q16795', 'P03901', 'O95299', 'O95182', 'O15239', 'P03923', 'P03915', 'O00483', 'P56556', 'O14561', 'O43678', 'P51970', 'O95167', 'O95169', 'O95298', 'O75438', 'P28331', 'O96000', 'O95168', 'O43676', 'O95178', 'P17568', 'Q9Y6M9', 'O75306', 'O43674', 'O43677', 'O95139', 'P56181', 'P09622', 'O75489', 'P00390', 'Q9UI09', 'O43920', 'O43181', 'P49821', 'P19404', 'Q9P0J0', 'Q16878', 'O75380', 'Q9NRX3', 'O00217', 'Q02928', 'P10515', 'P48728', 'Q15800', 'P09601', 'P30519', 'P05093', 'P14679']","A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). The action of supplemental NADH is unclear. Oral NADH supplementation has been used to combat simple fatigue as well as such mysterious and energy-sapping disorders as chronic fatigue syndrome and fibromyalgia. Researchers are also studying the value of NADH supplements for improving mental function in people with Alzheimer's disease, and minimizing physical disability and relieving depression in people with Parkinson's disease. Some healthy individuals also take NADH supplements orally to improve concentration and memory capacity, as well as to increase athletic endurance. However, to date there have been no published studies to indicate that using NADH is in any way effective or safe for these purposes.",NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=NC3=C(N)N=CN=C23)[C@@H](O)[C@H]1O,"NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.TargetActionsOrganismUUDP-glucose -dehydrogenaseNot AvailableHumansUAlcohol dehydrogenase ANot AvailableHumansUSorbitol dehydrogenaseNot AvailableHumansUAlcohol dehydrogenase Not AvailableHumansUAlcohol dehydrogenase CNot AvailableHumansUAlcohol dehydrogenase BNot AvailableHumansUAlcohol dehydrogenase class mu/sigma chainNot AvailableHumansUGlycerol--phosphate dehydrogenase [NAD(+)], cytoplasmicNot AvailableHumansUL-lactate dehydrogenase A-like ANot AvailableHumansUAlcohol dehydrogenase class-Not AvailableHumansUAldose reductaseNot AvailableHumansU-hydroxyacyl-CoA dehydrogenase type-Not AvailableHumansUMalate dehydrogenase, mitochondrialNot AvailableHumansUL-lactate dehydrogenase A chainNot AvailableHumansUNAD-dependent malic enzyme, mitochondrialNot AvailableHumansUPeroxisomal multifunctional enzyme type Not AvailableHumansUL-lactate dehydrogenase A-like BNot AvailableHumansUL-lactate dehydrogenase C chainNot AvailableHumansUL-lactate dehydrogenase B chainNot AvailableHumansUPeroxisomal bifunctional enzymeNot AvailableHumansUHydroxyacyl-coenzyme A dehydrogenase, mitochondrialNot AvailableHumansUNADP-dependent malic enzyme, mitochondrialNot AvailableHumansUD-beta-hydroxybutyrate dehydrogenase, mitochondrialNot AvailableHumansUMalate dehydrogenase, cytoplasmicNot AvailableHumansU-hydroxyisobutyrate dehydrogenase, mitochondrialNot AvailableHumansUTestosterone -beta-dehydrogenase Not AvailableHumansU-hydroxy--methylglutaryl-coenzyme A reductaseNot AvailableHumansUNADP-dependent malic enzymeNot AvailableHumansUD--phosphoglycerate dehydrogenaseNot AvailableHumansU-keto-steroid reductaseNot AvailableHumansUIsocitrate dehydrogenase [NAD] subunit gamma, mitochondrialNot AvailableHumansUIsocitrate dehydrogenase [NAD] subunit beta, mitochondrialNot AvailableHumansUIsocitrate dehydrogenase [NAD] subunit alpha, mitochondrialNot AvailableHumansUEstradiol -beta-dehydrogenase Not AvailableHumansUEstradiol -beta-dehydrogenase Not AvailableHumansU-cis retinol dehydrogenaseNot AvailableHumansUGDH/PGL endoplasmic bifunctional proteinNot AvailableHumansUEstradiol -beta-dehydrogenase Not AvailableHumansUAldo-keto reductase family member CNot AvailableHumansUInosine-'-monophosphate dehydrogenase Not AvailableHumansUAldo-keto reductase family member CNot AvailableHumansU-hydroxyprostaglandin dehydrogenase [NAD(+)]Not AvailableHumansUGDP-L-fucose synthaseNot AvailableHumansUAldo-keto reductase family member CNot AvailableHumansUCorticosteroid -beta-dehydrogenase isozyme Not AvailableHumansU beta-hydroxysteroid dehydrogenase/Delta -->-isomerase type Not AvailableHumansU beta-hydroxysteroid dehydrogenase/Delta -->-isomerase type Not AvailableHumansUInosine-'-monophosphate dehydrogenase Not AvailableHumansUTrifunctional enzyme subunit alpha, mitochondrialNot AvailableHumansUAldehyde dehydrogenase, mitochondrialNot AvailableHumansUCorticosteroid -beta-dehydrogenase isozyme Not AvailableHumansUAldo-keto reductase family member CNot AvailableHumansUSterol--alpha-carboxylate -dehydrogenase, decarboxylatingNot AvailableHumansUAldehyde dehydrogenase family member BNot AvailableHumansUMethylmalonate-semialdehyde dehydrogenase [acylating], mitochondrialNot AvailableHumansUAldehyde dehydrogenase, dimeric NADP-preferringNot AvailableHumansURetinal dehydrogenase Not AvailableHumansUGlyceraldehyde--phosphate dehydrogenase, testis-specificNot AvailableHumansU-trimethylaminobutyraldehyde dehydrogenaseNot AvailableHumansUAldehyde dehydrogenase family member ANot AvailableHumansUAldehyde dehydrogenase X, mitochondrialNot AvailableHumansUAldehyde dehydrogenase family member BNot AvailableHumansUGlyceraldehyde--phosphate dehydrogenaseNot AvailableHumansURetinal dehydrogenase Not AvailableHumansUFatty aldehyde dehydrogenaseNot AvailableHumansUSuccinate-semialdehyde dehydrogenase, mitochondrialNot AvailableHumansUAlpha-aminoadipic semialdehyde dehydrogenaseNot AvailableHumansUFlavin reductase (NADPH)Not AvailableHumansUPyrroline--carboxylate reductase Not AvailableHumansUPyrroline--carboxylate reductase , mitochondrialNot AvailableHumansUGlutamate dehydrogenase , mitochondrialNot AvailableHumansUPyruvate dehydrogenase E component subunit beta, mitochondrialNot AvailableHumansUPyruvate dehydrogenase E component subunit alpha, testis-specific form, mitochondrialNot AvailableHumansUPyruvate dehydrogenase E component subunit alpha, somatic form, mitochondrialNot AvailableHumansUBiliverdin reductase ANot AvailableHumansUShort-chain specific acyl-CoA dehydrogenase, mitochondrialNot AvailableHumansUDihydrofolate reductaseNot AvailableHumansU-oxoglutarate dehydrogenase, mitochondrialNot AvailableHumansUGlutamate dehydrogenase , mitochondrialNot AvailableHumansU-dehydrocholesterol reductaseNot AvailableHumansURibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHumansUNADH-ubiquinone oxidoreductase chain binderHumansUAlpha-aminoadipic semialdehyde synthase, mitochondrialNot AvailableHumansUNADH-ubiquinone oxidoreductase chain binderHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein , mitochondrialNot AvailableHumansUC--tetrahydrofolate synthase, cytoplasmicNot AvailableHumansUBifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialNot AvailableHumansUDelta--pyrroline--carboxylate dehydrogenase, mitochondrialNot AvailableHumansUNADH-cytochrome b reductase Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH-ubiquinone oxidoreductase chain Not AvailableHumansUDihydropteridine reductaseNot AvailableHumansUNADH-ubiquinone oxidoreductase chain binderHumansUNAD(P) transhydrogenase, mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit , mitochondrialNot AvailableHumansUNADH-ubiquinone oxidoreductase chain LNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH-ubiquinone oxidoreductase chain Not AvailableHumansUNADH-ubiquinone oxidoreductase chain Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUAcyl carrier protein, mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] subunit CNot AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH-ubiquinone oxidoreductase kDa subunit, mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] subunit C, mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] beta subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] flavoprotein , mitochondrialNot AvailableHumansUDihydrolipoyl dehydrogenase, mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein , mitochondrialNot AvailableHumansUGlutathione reductase, mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein Not AvailableHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] flavoprotein , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] flavoprotein , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit Not AvailableHumansUCysteine dioxygenase type Not AvailableHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein , mitochondrialNot AvailableHumansUNADH dehydrogenase [ubiquinone] alpha subcomplex subunit -like Not AvailableHumansUNADH dehydrogenase [ubiquinone] iron-sulfur protein , mitochondrialNot AvailableHumansUCytochrome P ANot AvailableHumansUDihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrialNot AvailableHumansUAminomethyltransferase, mitochondrialNot AvailableHumansUMethylsterol monooxygenase Not AvailableHumansUHeme oxygenase Not AvailableHumansUHeme oxygenase Not AvailableHumansUSteroid -alpha-hydroxylase/, lyaseNot AvailableHumansUTyrosinaseNot AvailableHumans","['Nutritional supplementation', 'Vitamin supplementation']","['Adenine Nucleotides', 'Coenzymes', 'Dietary Supplements', 'Enzymes and Coenzymes', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleotides', 'Purine Nucleotides', 'Purines', 'Ribonucleotides', 'Supplements']" +DB00843,Donepezil,Donepezilis an acetylcholinesterase inhibitor used to treat the behavioral and cognitive effects of Alzheimer's Disease and other types of dementia.,"['P22303', 'P28223', 'P06276', 'P29475', 'P98066', 'P01584', 'Q00653', 'P19838', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391']","By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis.8,15",COC1=C(OC)C=C2C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)CC2=C1,"The commonly accepted cholinergic hypothesisproposes that a portion of the cognitive and behavioral decline associated with Alzheimer's are the result of decreased cholinergic transmission in the central nervous system. Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which relieves the symptoms of Alzheimer's dementia. In addition to the above, other mechanisms of action of donepezil are possible, including the opposition of glutamate-induced excitatory transmission via downregulation of NMDA receptors and the regulation of amyloid proteins, which have demonstrated significant effects on the disease process of Alzheimer's.,,Other possible targets for donepezil may also include the inhibition various inflammatory signaling pathways, exerting neuroprotective effects.,TargetActionsOrganismAAcetylcholinesteraseinhibitorHumansU-hydroxytryptamine receptor AinducerHumansUCholinesteraseinducerHumansUNitric oxide synthase, braininhibitorinducerHumansUTumor necrosis factor-inducible gene proteininhibitorHumansUInterleukin- betainhibitorinducerHumansUNuclear factor NF-kappa-BinhibitorHumansUNMDA receptordownregulatorHumans",[],"['Anti-Dementia Drugs', 'BCRP/ABCG2 Substrates', 'Bradycardia-Causing Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Indans', 'Indenes', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Neurotransmitter Agents', 'Nootropic Agents', 'Parasympathomemetic (Cholinergic) Agents', 'Piperidines', 'Psychoanaleptics']" +DB00126,Vitamin C,Vitamin Cis a vitamin used to correct vitamin C deficiency and to increase the intestinal absorption of iron.,"['Q54873', 'P24300', 'O00469', 'O14832', 'O60568', 'O75936', 'P09172', 'P19021', 'Q32P28', 'Q8IVL5', 'Q8IVL6', 'P13674', 'Q8N543', 'Q6N063', 'Q6NS38', 'Q96Q83', 'Q9BY66', 'Q02809', 'Q9NVH6', 'Q9NXG6', 'Q9GZT9', 'Q96KS0', 'Q9H6Z9']","Ascorbic Acid (vitamin C) is a water-soluble vitamin indicated for the prevention and treatment of scurvy, as ascorbic acid deficiency results in scurvy. Collagenous structures are primarily affected, and lesions develop in bones and blood vessels. Administration of ascorbic acid completely reverses the symptoms of ascorbic acid deficiency.",[H][C@@]1(OC(=O)C(O)=C1O)[C@@H](O)CO,"In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair by acting as a cofactor in the posttranslational formation of -hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. Ascorbic acid is reversibly oxidized to dehydroascorbic acid in the body. These two forms of the vitamin are believed to be important in oxidation-reduction reactions. The vitamin is involved in tyrosine metabolism, conversion of folic acid to folinic acid, carbohydrate metabolism, synthesis of lipids and proteins, iron metabolism, resistance to infections, and cellular respiration.TargetActionsOrganismUHyaluronate lyaseinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)UDNAcleavageHumansUXylose isomerasesubstrateStreptomyces rubiginosusUProcollagen-lysine,-oxoglutarate -dioxygenase cofactorHumansUPhytanoyl-CoA dioxygenase, peroxisomalcofactorHumansUProcollagen-lysine,-oxoglutarate -dioxygenase cofactorHumansUGamma-butyrobetaine dioxygenasecofactorHumansUDopamine beta-hydroxylasecofactorHumansUPeptidyl-glycine alpha-amidating monooxygenasecofactorHumansUProlyl -hydroxylase cofactorHumansUProlyl -hydroxylase cofactorHumansUProlyl -hydroxylase cofactorHumansUProlyl -hydroxylase subunit alpha-cofactorHumansU-oxoglutarate and iron-dependent oxygenase domain-containing protein cofactorHumansU-oxoglutarate and iron-dependent oxygenase domain-containing protein cofactorHumansUAlpha-ketoglutarate-dependent dioxygenase alkB homolog activatorHumansUAlpha-ketoglutarate-dependent dioxygenase alkB homolog activatorHumansULysine-specific demethylase DcofactorHumansUProcollagen-lysine,-oxoglutarate -dioxygenase cofactorHumansUTrimethyllysine dioxygenase, mitochondrialcofactorHumansUTransmembrane prolyl -hydroxylasecofactorHumansUEgl nine homolog cofactorHumansUEgl nine homolog cofactorHumansUEgl nine homolog cofactorHumans","['Nutritional supplementation', 'Vitamin supplementation']","['Acids, Acyclic', 'Alimentary Tract and Metabolism', 'Antioxidants', 'Biological Factors', 'Carbohydrates', 'Compounds used in a research, industrial, or household setting', 'Diet, Food, and Nutrition', 'Food', 'Gastrointestinal Acidifying Agents', 'Genito Urinary System and Sex Hormones', 'Growth Substances', 'Gynecological Antiinfectives and Antiseptics', 'Hydroxy Acids', 'Micronutrients', 'Ophthalmologicals', 'Organic Acids', 'Physiological Phenomena', 'Protective Agents', 'Sensory Organs', 'Sugar Acids', 'Urinary Acidifying Agents', 'Vitamin C and analogues', 'Vitamins']" +DB00529,Foscarnet,"Foscarnetis an antiviral used to treat CMV, HIV, and HSV infections.","['P04293', 'P08546']","Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes virusesin vitroincluding cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro.",OC(=O)P(O)(O)=O,Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-ADNA polymerase catalytic subunitinhibitorHHV-,[],"['Acetates', 'Acids, Acyclic', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Chelating Activity', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Nephrotoxic agents', 'Nucleic Acid Synthesis Inhibitors', 'OAT1/SLC22A6 inhibitors', 'Organophosphonates', 'Organophosphorus Compounds', 'Phosphonic Acid Derivatives', 'Potential QTc-Prolonging Agents', 'Pyrophosphate Analog DNA Polymerase Inhibitor', 'QTc Prolonging Agents', 'Reverse Transcriptase Inhibitors']" +DB00459,Acitretin,Acitretinis an oral retinoid used in the treatment of severe psoriasis.,"['P19793', 'P10276', 'P10826', 'P13631', 'P28702', 'P48443', 'P09455']","Acitretin is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.",COC1=C(C)C(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1,"The mechanism of action of acitretin is unknown, however it is believed to work by targeting specific receptors (retinoid receptors such as RXR and RAR) in the skin which help normalize the growth cycle of skin cells.TargetActionsOrganismARetinoic acid receptor RXR-alphaagonistHumansARetinoic acid receptor alphaagonistHumansARetinoic acid receptor betaagonistHumansARetinoic acid receptor gammaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor RXR-gammaagonistHumansURetinol-binding protein agonistHumansURetinoic acid receptor RXRNot Available",[],"['Alkenes', 'Antipsoriatics', 'Antipsoriatics for Systemic Use', 'Biological Factors', 'Carotenoids', 'Cyclohexanes', 'Cyclohexenes', 'Cycloparaffins', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Hepatotoxic Agents', 'Hydrocarbons, Acyclic', 'Keratolytic Agents', 'Misc. Skin and Mucous Membrane Agents', 'Photosensitizing Agents', 'Pigments, Biological', 'Polyenes', 'Retinoids', 'Retinoids for Treatment of Psoriasis', 'Terpenes']" +DB00959,Methylprednisolone,"Methylprednisoloneis a corticosteroid used to treat inflammation or immune reactions across a variety of organ systems, endocrine conditions, and neoplastic diseases.","['P04150', 'P04083']","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.5Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.5Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.5",[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUAnnexin AagonistHumans",['Palliative Treatment'],"['Adrenal Cortex Hormones', 'Adrenals', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Inflammatory Agents', 'Antiemetics', 'Antineoplastic Agents', 'Autonomic Agents', 'Central Nervous System Agents', 'Compounds used in a research, industrial, or household setting', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Weak (Group I)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Experimental Unapproved Treatments for COVID-19', 'Fused-Ring Compounds', 'Gastrointestinal Agents', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Neuroprotective Agents', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Protective Agents', 'Sensory Organs', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB00722,Lisinopril,"Lisinoprilis an ACE inhibitor used to treat hypertension, heart failure, and acute myocardial infarction.","['P12821', 'P00797']","Lisinopril is an angiotensin converting enzyme inhibitor used to treat hypertension, heart failure, and myocardial infarction.8,9,10Lisinopril is not a prodrug, and functions by inhibition of angiotensin converting enzyme as well as the renin angiotensin aldosterone system.3,4,5It has a wide therapeutic index and a long duration of action as patients are generally given 10-80mg daily.8,9,10",NCCCC[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N1CCC[C@H]1C(O)=O,"Angiotensin II constricts coronary blood vessels and is positively inotropic, which under normal circumstances, would increase vascular resistance and oxygen consumption.This action can eventually lead to myocyte hypertrophy and vascular smooth muscle cell proliferation.Lisinopril is an angiotensin converting enzyme inhibitor (ACEI), preventing the conversion of angiotensin I to angiotensin II.,This action prevents myocyte hypertrophy and vascular smooth muscle cell proliferation seen in untreated patients.Increased levels of bradykinin also exhibit vasodilating effects for patients taking ACEIs.Lisinopril also inhibits renin's conversion of angiotensin to angiotensin I.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumansURenininhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Amino Acids, Peptides, and Proteins', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Dipeptides', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Lipid Modifying Agents', 'Oligopeptides', 'Peptides', 'Photosensitizing Agents', 'Protease Inhibitors', 'Protective Agents']" +DB00668,Epinephrine,"Epinephrineis a hormone and neurotransmitter used to treat allergic reactions, to restore cardiac rhythm, and to control mucosal congestion, glaucoma, and asthma.","['P35348', 'P35368', 'P08588', 'P07550', 'P08913', 'P18089', 'P25100', 'P01375']","Epinephrine is a sympathomimetic drug. It causes an adrenergic receptive mechanism on effector cells and mimics all actions of the sympathetic nervous system except those on the facial arteries and sweat glands18.Important effects of epinephrine include increased heart rate, myocardial contractility, and renin release via beta-1 receptors. Beta-2 effects produce bronchodilation which may be useful as an adjunct treatment of asthma exacerbations as well as vasodilation, tocolysis, and increased aqueous humor production15. In croup, nebulized epinephrine is associated with both clinically and statistically significant transient reduction of croup symptoms 30 minutes post-treatment7. Epinephrine also alleviates pruritus, urticaria, and angioedema and may be helpful in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxing effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladderLabel.",CNC[C@H](O)C1=CC(O)=C(O)C=C1,"Epinephrine acts on alpha and beta-adrenergic receptors. Epinephrine acts on alpha and beta receptors and is the strongest alpha receptor activator. Through its action on alpha-adrenergic receptors, epinephrine minimizes the vasodilation and increased the vascular permeability that occurs during anaphylaxis, which can cause the loss of intravascular fluid volume as well as hypotension. Epinephrine relaxes the smooth muscle of the bronchi and iris and is a histamine antagonist, rendering it useful in treating the manifestations of allergic reactions and associated conditions. This drug also produces an increase in blood sugar and increases glycogenolysis in the liver. Through its action on beta-adrenergic receptors, epinephrine leads to bronchial smooth muscle relaxation that helps to relieve bronchospasm, wheezing, and dyspnea that may occur during anaphylaxisLabel.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansUAlpha-D adrenergic receptorantagonistHumansUTumor necrosis factorantagonistagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Adrenergic beta-1 Receptor Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-3 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alpha-and Beta-adrenergic Agonists', 'Amines', 'Anti-Asthmatic Agents', 'Antiglaucoma Preparations and Miotics', 'Autonomic Agents', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Bronchodilator Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'COMT Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dental Agents', 'Drugs for Obstructive Airway Diseases', 'Epinephrine and similars', 'Hemostatics', 'Hyperglycemia-Associated Agents', 'Local Hemostatics', 'Mydriatics', 'Nasal Preparations', 'Neurotransmitter Agents', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenols', 'Respiratory System Agents', 'Stomatological Preparations', 'Sympathomimetic (Adrenergic) Agents', 'Sympathomimetics', 'Sympathomimetics in Glaucoma Therapy', 'Sympathomimetics, Plain', 'Vasoconstrictor Agents']" +DB01593,Zinc,Zincis an essential element commonly used for the treatment of patients with documented zinc deficiency.,"['P46663', 'P16455', 'P04075', 'P68104', 'P06733', 'O14556', 'P15531', 'P07237', 'P30101', 'Q06830', 'P78330', 'P60174', 'P49411', 'P03372', 'P08700', 'P02795', 'O14618', 'Q13547', 'P56524', 'P29372', 'P04279', 'P00441', 'Q9BY41', 'O15304', 'P23415', 'Q00987', 'P01308', 'P46939', 'P45381', 'P05109', 'P06702', 'P14780', 'O15350', 'P29034', 'P04637', 'P25713', 'O75340', 'Q8N907', 'P04731', 'P04217', 'P01023', 'P01019', 'P02765', 'P02743', 'P02647', 'P02652', 'P06727', 'Q0VD83', 'P02649', 'O14791', 'P02746', 'P02747', 'P00736', 'P09871', 'P01024', 'P0C0L5', 'P04003', 'P20851', 'P01031', 'P46736', 'P07357', 'P07358', 'P07360', 'P00751', 'P08603', 'P05156', 'P10909', 'P00450', 'P15169', 'P22792', 'P81605', 'P15924', 'P00748', 'P05160', 'P00734', 'O75636', 'P02671', 'P02751', 'P06396', 'P69905', 'P68871', 'P00739', 'Q86YZ3', 'P35858', 'P01876', 'P01871', 'P01599', 'P01619', 'P80748', 'P19827', 'P19823', 'Q06033', 'Q14624', 'P01591', 'P14923', 'P03952', 'P01042', 'P04264', 'P13645', 'P02533', 'P08779', 'P35908', 'P13647', 'P02538', 'P35527', 'P19652', 'Q96PD5', 'P27169', 'P20742', 'P31151', 'P49908', 'P01009', 'P01011', 'P29622', 'P08185', 'P05546', 'P04278', 'P02787', 'P02766', 'P04004', 'P51693', 'Q06481', 'P05067', 'P09874']","Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations30.Studies on oral zinc for specific conditions shows the following evidence in various conditions13:Colds:Evidence suggests that if zinc lozenges or syrup are taken within 24 hours after cold symptoms start, the supplement may shorten the length of colds. The use intranasal zinc has been associated with the loss of the sense of smell, in some cases long-term or permanently13.Wound healing:Patients with skin ulcers and decreased levels of zinc may benefit from oral zinc supplements13.Diahrrea: Oral zinc supplements can reduce the symptoms of diarrhea in children with low levels of zinc, especially in cases of malnutrition13.",[Zn],"Zinc has three primary biological roles:catalytic,structural, andregulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately human proteins including enzymes, nuclear factors, and hormones.Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins.In HL- cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-beta, and IL-.There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine --cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to September .Zinc deficiency in humans decreases the activity of serumthymulin(a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper (Th()) cytokines are decreased but T-helper (Th()) cytokines are not affected by zinc deficiency in humans.The change ofTh()toTh()function leads to cell-mediated immune dysfunction. Because IL- production (Th() cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells.In humans, zinc deficiency may lead to the generation of new CD+ T cells, produced in the thymus. In cell culture studies (HUT-, a Th() human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th() cytokine production.In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers. In HL- cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-beta, and IL- cytokines and mRNA. In such cells, zinc was found to induce A, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers.The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels.TargetActionsOrganismUB bradykinin receptorNot AvailableHumansUMethylated-DNA--protein-cysteine methyltransferaseNot AvailableHumansUFructose-bisphosphate aldolase ANot AvailableHumansUElongation factor -alpha Not AvailableHumansUAlpha-enolaseNot AvailableHumansUGlyceraldehyde--phosphate dehydrogenase, testis-specificNot AvailableHumansUNucleoside diphosphate kinase ANot AvailableHumansUProtein disulfide-isomeraseNot AvailableHumansUProtein disulfide-isomerase ANot AvailableHumansUPeroxiredoxin-Not AvailableHumansUPhosphoserine phosphataseNot AvailableHumansUTriosephosphate isomeraseNot AvailableHumansUElongation factor Tu, mitochondrialNot AvailableHumansUEstrogen receptor alphacofactorHumansUInterleukin-Not AvailableHumansUMetallothionein-Not AvailableHumansUCopper chaperone for superoxide dismutaseNot AvailableHumansUHistone deacetylase cofactorHumansUHistone deacetylase cofactorHumansUDNA--methyladenine glycosylaseNot AvailableHumansUSemenogelin-Not AvailableHumansUSuperoxide dismutase [Cu-Zn]Not AvailableHumansUHistone deacetylase cofactorHumansUApoptosis regulatory protein SivaNot AvailableHumansUGlycine receptor subunit alpha-Not AvailableHumansUE ubiquitin-protein ligase MdmNot AvailableHumansUInsulinNot AvailableHumansUUtrophinNot AvailableHumansUAspartoacylasecofactorHumansUProtein S-ANot AvailableHumansUProtein S-ANot AvailableHumansUMatrix metalloproteinase-Not AvailableHumansUTumor protein pcofactorHumansUProtein S-ANot AvailableHumansUCellular tumor antigen pNot AvailableHumansUMetallothionein-Not AvailableHumansUProgrammed cell death protein Not AvailableHumansUDAN domain family member cofactorHumansUMetallothionein-ANot AvailableHumansUAlpha-B-glycoproteinNot AvailableHumansUAlpha--macroglobulinNot AvailableHumansUAngiotensinogenNot AvailableHumansUAlpha--HS-glycoproteinNot AvailableHumansUSerum amyloid P-componentNot AvailableHumansUApolipoprotein A-INot AvailableHumansUApolipoprotein A-IINot AvailableHumansUApolipoprotein A-IVNot AvailableHumansUApolipoprotein B receptorNot AvailableHumansUApolipoprotein ENot AvailableHumansUApolipoprotein LNot AvailableHumansUComplement Cq subcomponent subunit BNot AvailableHumansUComplement Cq subcomponent subunit CNot AvailableHumansUComplement Cr subcomponentNot AvailableHumansUComplement Cs subcomponentNot AvailableHumansUComplement CNot AvailableHumansUComplement C-BNot AvailableHumansUCb-binding protein alpha chainNot AvailableHumansUCb-binding protein beta chainNot AvailableHumansUComplement CNot AvailableHumansULys--specific deubiquitinase BRCCNot AvailableHumansUComplement component C alpha chainNot AvailableHumansUComplement component C beta chainNot AvailableHumansUComplement component C gamma chainNot AvailableHumansUComplement factor BNot AvailableHumansUComplement factor HNot AvailableHumansUComplement factor INot AvailableHumansUClusterinNot AvailableHumansUCeruloplasminNot AvailableHumansUCarboxypeptidase N catalytic chainNot AvailableHumansUCarboxypeptidase N subunit Not AvailableHumansUDermcidinNot AvailableHumansUDesmoplakinNot AvailableHumansUCoagulation factor XIINot AvailableHumansUCoagulation factor XIII B chainNot AvailableHumansUProthrombinNot AvailableHumansUFicolin-Not AvailableHumansUFibrinogen alpha chainNot AvailableHumansUFibronectinNot AvailableHumansUGelsolinNot AvailableHumansUHemoglobin subunit alphaNot AvailableHumansUHemoglobin subunit betaNot AvailableHumansUHaptoglobin-related proteinNot AvailableHumansUHornerinNot AvailableHumansUInsulin-like growth factor-binding protein complex acid labile subunitNot AvailableHumansUIg alpha- chain C regionNot AvailableHumansUIg mu chain C regionNot AvailableHumansUImmunoglobulin kappa variable -Not AvailableHumansUIg kappa chain V-III region GOLNot AvailableHumansUImmunoglobulin lambda variable -Not AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUImmunoglobulin J chainNot AvailableHumansUJunction plakoglobinNot AvailableHumansUPlasma kallikreinNot AvailableHumansUKininogen-Not AvailableHumansUKeratin, type II cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type II cytoskeletal epidermalNot AvailableHumansUKeratin, type II cytoskeletal Not AvailableHumansUKeratin, type II cytoskeletal ANot AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUAlpha--acid glycoprotein Not AvailableHumansUN-acetylmuramoyl-L-alanine amidaseNot AvailableHumansUSerum paraoxonase/arylesterase Not AvailableHumansUPregnancy zone proteinNot AvailableHumansUProtein S-ANot AvailableHumansUSelenoprotein PNot AvailableHumansUAlpha--antitrypsinNot AvailableHumansUAlpha--antichymotrypsinNot AvailableHumansUKallistatinNot AvailableHumansUCorticosteroid-binding globulinNot AvailableHumansUHeparin cofactor Not AvailableHumansUSex hormone-binding globulinNot AvailableHumansUSerotransferrinNot AvailableHumansUTransthyretinNot AvailableHumansUVitronectinNot AvailableHumansUAmyloid-like protein cofactorHumansUAmyloid-like protein cofactorHumansUAmyloid beta A proteincofactorHumansUPoly [ADP-ribose] polymerase Not AvailableHumans","['Dietary and Nutritional Therapies', 'Dietary supplementation']","['Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Diet, Food, and Nutrition', 'Elements', 'Food', 'Metal cations', 'Metal divalent cations', 'Metals', 'Metals, Heavy', 'Micronutrients', 'Minerals', 'Physiological Phenomena', 'Trace Elements', 'Transition Elements', 'Vasoprotectives', 'Zinc Compounds']" +DB00389,Carbimazole,Carbimazoleis a drug used for the reduction of thyroid function.,['P07202'],Carbimazole is a carbethoxy derivative of methimazole. Its antithyroid action is due to its conversion to methimazole after absorption. It is used to treat hyperthyroidism and thyrotoxicosis.,CCOC(=O)N1C=CN(C)C1=S,"Carbimazole is an aitithyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T and T.TargetActionsOrganismAThyroid peroxidaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Antithyroid agents', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazoles', 'Sulfur-Containing Imidazole Derivatives', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroid Products']" +DB00977,Ethinylestradiol,Ethinylestradiolis an estradiol used as a contraceptive.,"['P03372', 'O75469']","Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation.13,12,15It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects.15Patients should be counselled regarding the risks of thrombotic events.15",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3,"Ethinylestradiol is a synthetic estrogenic compound.Use of estrogens have a number of effects on the body including reduced bone density.Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg.,Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium.It also increases sex hormone binding globulin.TargetActionsOrganismAEstrogen receptor alphaagonistHumansUNuclear receptor subfamily group I member agonistHumans","['Contraception', 'Folate supplementation therapy']","['Adrenal Cortex Hormones', 'Antineoplastic and Immunomodulating Agents', 'BSEP/ABCB11 inducers', 'BSEP/ABCB11 Inhibitors', 'COMT Substrates', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Contraceptives, Postcoital', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Estradiol Congeners', 'Estrogen Contraceptives', 'Estrogenic Steroids, Alkylated', 'Estrogens', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Natural and Semisynthetic Estrogens, Plain', 'Norpregnanes', 'Norpregnatrienes', 'Norsteroids', 'P-glycoprotein substrates', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Thyroxine-binding globulin inducers', 'UGT1A1 Inducers', 'UGT1A1 Substrates', 'UGT1A4 substrates', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB00717,Norethisterone,"Norethisteroneis a synthetic second-generation progestin used for contraception, prevention of endometrial hyperplasia in hormone replacement therapy, and in the treatment of other hormone-mediated illnesses such as endometriosis.","['P06401', 'P10275', 'P04150']","Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation.14A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses.14",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H],"On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes.Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system.Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration.Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation.,Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development.When used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium.As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies.Norethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor.,While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes).TargetActionsOrganismAProgesterone receptoragonistHumansUAndrogen receptoragonistHumansUGlucocorticoid receptoragonistHumans","['Contraception', 'Hormone Replacement Therapy', 'Oral Contraceptives']","['Adrenal Cortex Hormones', 'Anti-Gonadotropin-Releasing Hormones', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Contraceptives, Oral, Synthetic', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Estren Derivatives', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hyperglycemia-Associated Agents', 'Hypothalamic Hormones', 'Norpregnenes', 'Norsteroids', 'P-glycoprotein inhibitors', 'Pituitary and Hypothalamic Hormones and Analogues', 'Progestin Contraceptives', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB00763,Methimazole,"Methimazoleis a thionamide antithyroid agent that inhibits the actions of thyroid peroxidase, leading to a reduction in thyroid hormone synthesis and amelioration of hyperthyroidism.",['P07202'],"Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism.1819Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration.11The most serious potential side effect of methimazole therapy is agranulocytosis, and patients should be instructed to monitor for, and report, any signs or symptoms of agranulocytosis such as fever or sore throat. Other cytopenias may also occur during methimazole therapy. There also exists the potential for severe hepatic toxicity with the use of methimazole, and monitoring for signs and symptoms of hepatic dysfunction, such as jaundice, anorexia, pruritus, and elevation in liver transaminases, is prudent in patients using this therapy.18,19",CN1C=CNC1=S,"Methimazole's primary mechanism of action appears to be interference in an early step in thyroid hormone synthesis involving thyroid peroxidase (TPO), however the exact method through which methimazole inhibits this step is unclear.TPO, along with hydrogen peroxide, normally catalyzes the conversion of iodide to iodine and then further catalyzes the incorporation of this iodine onto the and/or positions of the phenol rings of tyrosine residues in thyroglobulin. These thyroglobulin molecules then degrade within thyroid follicular cells to form either thyroxine (T) or tri-iodothyronine (T), which are the main hormones produced by the thyroid gland.Methimazole may directly inhibit TPO, but has been shown in vivo to instead act as a competitive substrate for TPO, thus becoming iodinated itself and interfering with the iodination of thyroglobulin.Another proposed theory is that methimazole’s sulfur moiety may interact directly with the iron atom at the centre of TPO’s heme molecule, thus inhibiting its ability to iodinate tyrosine residues.Other proposed mechanisms with weaker evidence include methimazole binding directly to thyroglobulin or direct inhibition of thyroglobulin itself.TargetActionsOrganismAThyroid peroxidasesubstrateinhibitorHumans",[],"['Antithyroid agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (weak)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazoles', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Sulfur Compounds', 'Sulfur-Containing Imidazole Derivatives', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroid Hormone Synthesis Inhibitor', 'Thyroid Hormone Synthesis Inhibitors', 'Thyroid Products']" +DB01103,Quinacrine,An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.,"['O60733', 'P47712', 'Q15111']","Quinacrine has been used as an antimalarial drug and as an antibiotic. It is used to treat giardiasis, a protozoal infection of the intestinal tract, and certain types of lupus erythematosus, an inflammatory disease that affects the joints, tendons, and other connective tissues and organs. Quinacrine may be injected into the space surrounding the lungs to prevent reoccurrence of pneumothorax. The exact way in which quinacrine works is unknown. It appears to interfere with the parasite's metabolism.",CCN(CC)CCCC(C)NC1=C2C=C(OC)C=CC2=NC2=C1C=CC(Cl)=C2,"The exact mechanism of antiparasitic action is unknown; however, quinacrine binds to deoxyribonucleic acid (DNA) in vitro by intercalation between adjacent base pairs, inhibiting transcription and translation to ribonucleic acid (RNA). Quinacrine does not appear to localize to the nucleus of Giaridia trophozoites, suggesting that DNA binding may not be the primary mechanism of its antimicrobial action. Fluorescence studies using Giardia suggest that the outer membranes may be involved. Quinacrine inhibits succinate oxidation and interferes with electron transport. In addition, by binding to nucleoproteins, quinacrine suppress the lupus erythematous cell factor and acts as a strong inhibitor of cholinesterase.TargetActionsOrganismADNAintercalationHumansA/ kDa calcium-independent phospholipase AinhibitorHumansACytosolic phospholipase AinhibitorHumansAInactive phospholipase C-like protein inhibitorHumans",[],"['Acridines', 'Aminoacridines', 'Anti-Infective Agents', 'Anticestodal Agents', 'Antimalarials', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiplatyhelmintic Agents', 'Antiprotozoals', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors']" +DB00943,Zalcitabine,Zalcitabineis a dideoxynucleoside used to treat HIV.,['Q72547'],Zalcitabine is an analog of 2'-deoxycytidine that is pharmacologically related to but structurally different from other nucleotide reverse transcriptase inhibitors (NRTIs). Zalcitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.,NC1=NC(=O)N(C=C1)[C@H]1CC[C@@H](CO)O1,"Zalcitabine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type (HIV-). Within cells, zalcitabine is converted to its active metabolite, dideoxycytidine '-triphosphate (ddCTP), by the sequential action of cellular enzymes. ddCTP interferes with viral RNA-directed DNA polymerase (reverse transcriptase) by competing for utilization of the natural substrate deoxycytidine '-triphosphate (dCTP), as well as incorpating into viral DNA. Due to it's lack of a '-OH group, the formation of a ' to ' phosphodiester linkage that is necessary for DNA chain elongation is inhibited, thus leading to the termination of viral DNA growth.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Deoxycytidine', 'Deoxyribonucleosides', 'Dideoxynucleosides', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'OAT1/SLC22A6 Substrates', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Reverse Transcriptase Inhibitors', 'Toxic Actions']" +DB00115,Vitamin B12,Vitamin B12is a vitamin available in many formulations to correct vitamin B12 deficiency.,"['Q99707', 'P22033', 'Q9UBK8', 'Q8IVH4', 'Q9Y4U1', 'P42898']","General effectsCyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B1210.Parenteral cyanocobalamin effectsThe parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition20.Nasal spray effectsIn 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L)Label.",C[C@H](CNC(=O)CC[C@]1(C)[C@@H](CC(N)=O)[C@H]2N=C1\C(C)=C1/N=C(/C=C3\N=C(\C(\C)=C4\[C@@H](CCC(N)=O)[C@](C)(CC(N)=O)[C@@]2(C)N4[Co+]C#N)[C@@](C)(CC(N)=O)[C@@H]3CCC(N)=O)C(C)(C)[C@@H]1CCC(N)=O)OP([O-])(=O)O[C@@H]1[C@@H](CO)O[C@@H]([C@@H]1O)N1C=NC2=C1C=C(C)C(C)=C2,"Vitamin B serves as a cofactor formethionine synthaseandL-methylmalonyl-CoA mutaseenzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA tosuccinyl-CoAin the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin.In tissues, vitamin B is required for the synthesis ofmethioninefrom homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B, tetrahydrofolate cannot be regenerated from -methyltetrahydrofolate, and this can lead to functional folate deficiency,Label. +This reaction is dependent on methylcobalamin (vitamin B) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to formmethionineandtetrahydrofolate. Vitamin B incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B and the interruption of this reaction leads to the development of megaloblastic anemia.TargetActionsOrganismAMethionine synthasecofactorHumansAMethylmalonyl-CoA mutase, mitochondrialcofactorHumansUMethionine synthase reductasecofactorHumansUMethylmalonic aciduria type A protein, mitochondrialbinderHumansUMethylmalonic aciduria and homocystinuria type C proteincofactorHumansUMethylenetetrahydrofolate reductasecofactorHumans","['Nutritional supplementation', 'Vitamin supplementation']","['Antianemic Preparations', 'Blood and Blood Forming Organs', 'Corrinoids', 'Diet, Food, and Nutrition', 'Drugs that are Mainly Renally Excreted', 'Food', 'Growth Substances', 'Heterocyclic Compounds, Fused-Ring', 'Micronutrients', 'Vitamin B 12, biosynthesis', 'Vitamin B Complex', 'Vitamin B12 and Folic Acid', 'Vitamins']" +DB01159,Halothane,Halothaneis a general inhalation anesthetic used for the induction and maintenance of general anesthesia.,"['O14649', 'Q9NPC2', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P20020', 'Q01814', 'Q16720', 'P23634', 'Q12791', 'Q8TCU5', 'O60391', 'Q12879', 'P23415', 'P08100', 'P48051', 'P48549', 'P03886', 'O15554', 'P14867', 'P59768', 'Q6W5P4']",Halothane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It reduces the blood pressure and frequently decreases the pulse rate and depresses respiration. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.,[H]C(Cl)(Br)C(F)(F)F,"Halothane causes general anaethesia due to its actions on multiple ion channels, which ultimately depresses nerve conduction, breathing, cardiac contractility. Its immobilizing effects have been attributed to its binding to potassium channels in cholinergic neurons. Halothane's effect are also likely due to binding to NMDA and calcium channels, causing hyperpolarization.TargetActionsOrganismAPotassium channel subfamily K member binderHumansAPotassium channel subfamily K member binderHumansAGABA(A) Receptorpositive allosteric modulatorHumansAPlasma membrane calcium-transporting ATPaseinhibitorHumansUCalcium-activated potassium channel subunit alpha-inhibitorHumansUGlutamate receptor ionotropic, NMDA AantagonistHumansUGlutamate receptor ionotropic, NMDA BantagonistHumansUGlutamate receptor ionotropic, NMDA AantagonistHumansUGlycine receptor subunit alpha-allosteric modulatorHumansURhodopsinotherHumansUG protein-activated inward rectifier potassium channel inhibitorHumansUG protein-activated inward rectifier potassium channel inhibitorHumansUNADH-ubiquinone oxidoreductase chain inhibitorHumansUIntermediate conductance calcium-activated potassium channel protein inhibitorHumansUGamma-aminobutyric acid receptor subunit alpha-other/unknownHumansUGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-other/unknownHumansUNeuropeptide S receptorother/unknownHumans",[],"['Agents that produce hypertension', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Inhalation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Hydrocarbons, Halogenated', 'Hypotensive Agents', 'Nervous System', 'NMDA Receptor Antagonists']" +DB01234,Dexamethasone,"Dexamethasoneis a glucocorticoid available in various modes of administration that is used for the treatment of various inflammatory conditions, including bronchial asthma, as well as endocrine and rheumatic disorders.","['P04150', 'P51843', 'P04083', 'P35228', 'O75469']","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.3Dexamethasone's duration of action varies depending on the route.12,13,14,15,16,17,18,19,20,21Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.3Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.3",[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUNuclear receptor subfamily group B member stimulatorHumansUAnnexin AagonistHumansUNitric oxide synthase, induciblenegative modulatorHumansUNuclear receptor subfamily group I member agonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents Causing Muscle Toxicity', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Alimentary Tract and Metabolism', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Inflammatory Agents', 'Antiemetics', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Autonomic Agents', 'BCRP/ABCG2 Inhibitors', 'BSEP/ABCB11 inducers', 'Central Nervous System Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids for Local Oral Treatment', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Moderately Potent (Group II)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (moderate)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Experimental Unapproved Treatments for COVID-19', 'Fused-Ring Compounds', 'Gastrointestinal Agents', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Inducers of Drug Clearance', 'Nasal Preparations', 'OAT3/SLC22A8 Substrates', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Otologicals', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Sensory Organs', 'Steroids', 'Steroids, Fluorinated', 'Stomatological Preparations', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Vasoprotectives']" +DB00631,Clofarabine,Clofarabineis a purine nucleoside used to treat relapsed or refractory acute lymphoblastic leukemia in patients 1 to 21 years old.,"['P09884', 'P23921']","Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells.",[H][C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C=NC2=C(N)N=C(Cl)N=C12,"Clofarabine is metabolized intracellularly to the active '-monophosphate metabolite by deoxycytidine kinase and '-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine '-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.TargetActionsOrganismADNAother/unknownHumansADNA polymerase alpha catalytic subunitinhibitorHumansARibonucleoside-diphosphate reductase large subunitinhibitorHumans",[],"['Adenine Nucleotides', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Arabinonucleosides', 'BCRP/ABCG2 Substrates', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'Nucleotides', 'OAT3/SLC22A8 Substrates', 'OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index', 'OCT2 Substrates with a Narrow Therapeutic Index', 'Purine Analogues', 'Purine Nucleotides', 'Purines', 'Ribonucleotides', 'Toxic Actions']" +DB00439,Cerivastatin,Cerivastatinis a statin (or HMG CoA reductase inhibitor) used with dietary changes to decrease lipid levels and reduce the risk of cardiovascular events.,['P04035'],"Cerivastatin, a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides, is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb).",COCC1=C(C2=CC=C(F)C=C2)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C(C(C)C)N=C1C(C)C,"Cerivastatin competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for converting HMG-CoA to mevalonate. As mevalonate is a precursor of sterols such as cholesterol, this results in a decrease in cholesterol in hepatic cells, upregulation of LDL-receptors, and an increase in hepatic uptake of LDL-cholesterol from the circulation.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein substrates', 'UGT1A1 Substrates']" +DB00394,Beclomethasone dipropionate,Beclomethasone dipropionateis an inhaled corticosteroid used as maintenance treatment in the prophylaxis of asthma attacks.,['P04150'],"Inflammatory conditions, including asthma, dermatoses, and allergic rhinitis, involve the activation of cascades by inflammatory mediators. Inflammation is a primary defense mechanism and the homeostatic response of the immune system; however, a prolonged inflammatory response in certain disorders may lead to tissue damage, pain, and swelling. Beclomethasone dipropionate works by attenuating the inflammatory responses associated with asthma, allergic rhinitis, nasal polyps, and corticosteroid-responsive dermatoses. It suppresses the actions of inflammatory cells, such as mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils. It also inhibits the release of inflammatory mediators, such as histamine, eicosanoids, leukotrienes, and cytokines.11Beclomethasone dipropionate is reported to exhibit potent topical activity while possessing low systemic effects.2Beclomethasone dipropionate is a corticosteroid drug with anti-inflammatory and vasoconstrictive effects used to treat chronic inflammatory processes such as asthma, allergic rhinitis, corticosteroid-responsive dermatoses. When inhaled, it improves lung function, decreases airway hyper-reactivity, and reduces the severity of asthmatic symptoms.9Although inhaled corticosteroids, including beclomethasone dipropionate, are reported to mainly act locally in the lungs, systemic effects such as disruption of hypothalamic-pituitary-adrenal (HPA) axis function, bone turnover, osteoporosis, and growth suppression may still be observed with chronic use or high dose administration. There were varying findings from clinical studies examining the effect of beclomethasone dipropionate on growth suppression in pediatric patients.9It was shown to suppress the hypothalamo-pituitary-adrenal (HPA) axis in a dose-dependent manner.6HPA axis is a central hormonal response system to stress and activation of HPA axis leads to the production of endogenous steroid hormone production.7Long-term use of high-dose systemic corticosteroids, including those inhaled, was often associated with signs and symptoms of adrenal insufficiency when exposed to stress conditions, such as trauma, surgery, or infections. As corticosteroids work by suppressing the immune system, there may be an increased risk for developing infections.11Cases ofCandida albicansinfection of the mouth and throat have been reported with inhaled beclomethasone dipropionate therapy.8",[H][C@@]12C[C@H](C)[C@](OC(=O)CC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Beclomethasone dipropionate is a corticosteroid and prodrug that is rapidly activated by hydrolysis to the active monoester, monopropionate (-BMP), which mediates anti-inflammatory actions. -BMP has been shownin vitroto exhibit a binding affinity for the human glucocorticoid receptor which is approximately times that of dexamethasone and times that of beclomethasone dipropionate.Upon binding of the ligand, the glucocorticoid receptors dimerize and translocate into the nucleus, where they subsequently bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, leading to changes in transcription. There are several proposed mechanisms for the anti-inflammatory action of corticosteroids. Corticosteroids may work by increasing the transcription of genes coding for anti-inflammatory proteins, including lipocortin- and interleukin-.Corticosteroids were also shown to inhibit the expression of multiple genes that encode pro-inflammatory factors, such as cytokines, chemokines, and adhesion molecules, that are activated during the chronic inflammatory process.This is thought to be due to the direct inhibitory interaction between activated glucocorticoid receptors and activated pro-inflammatory transcription factors, such as nuclear factor-kappa B and activator protein-.Chronic inflammation is often characterized by enhanced expression of these transcription factors that bind to and activate coactivator molecules, which then acetylate core histones to switch on gene transcription to further amplify the inflammatory process.Corticosteroids suppress the multiple inflammatory gene expression by promoting histone deacetylation, resulting in tighter coiling of DNA and reduced access of transcription factors to their binding sites.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents to Treat Airway Disease', 'Alimentary Tract and Metabolism', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'BCRP/ABCG2 Inhibitors', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids Acting Locally', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs for Obstructive Airway Diseases', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'Nasal Preparations', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Respiratory System Agents', 'Steroids', 'Steroids, Chlorinated', 'Thyroxine-binding globulin inhibitors']" +DB14487,Zinc acetate,Zinc acetateis a medication used to treat zinc deficiency.,"['P46663', 'P16455', 'P04075', 'P68104', 'P06733', 'O14556', 'P15531', 'P07237', 'P30101', 'Q06830', 'P78330', 'P60174', 'P49411', 'P03372', 'P08700', 'P02795', 'O14618', 'Q13547', 'P56524', 'P29372', 'P04279', 'P00441', 'Q9BY41', 'O15304', 'P23415', 'Q00987', 'P01308', 'P46939', 'P45381', 'P05109', 'P06702', 'P14780', 'O15350', 'P29034', 'P04637', 'P25713', 'O75340', 'Q8N907', 'P04731', 'P04217', 'P01023', 'P01019', 'P02765', 'P02743', 'P02647', 'P02652', 'P06727', 'Q0VD83', 'P02649', 'O14791', 'P02746', 'P02747', 'P00736', 'P09871', 'P01024', 'P0C0L5', 'P04003', 'P20851', 'P01031', 'P46736', 'P07357', 'P07358', 'P07360', 'P00751', 'P08603', 'P05156', 'P10909', 'P00450', 'P15169', 'P22792', 'P81605', 'P15924', 'P00748', 'P05160', 'P00734', 'O75636', 'P02671', 'P02751', 'P06396', 'P69905', 'P68871', 'P00739', 'Q86YZ3', 'P35858', 'P01876', 'P01871', 'P01599', 'P01619', 'P80748', 'P19827', 'P19823', 'Q06033', 'Q14624', 'P01591', 'P14923', 'P03952', 'P01042', 'P04264', 'P13645', 'P02533', 'P08779', 'P35908', 'P13647', 'P02538', 'P35527', 'P19652', 'Q96PD5', 'P27169', 'P20742', 'P31151', 'P49908', 'P01009', 'P01011', 'P29622', 'P08185', 'P05546', 'P04278', 'P02787', 'P02766', 'P04004', 'P51693', 'Q06481', 'P05067', 'P09874']","Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations29.Studies on oral zinc for specific conditions shows the following evidence in various conditions12:Colds:Evidence suggests that if zinc lozenges or syrup are taken within 24 hours after cold symptoms start, the supplement may shorten the length of colds. The use intranasal zinc has been associated with the loss of the sense of smell, in some cases long-term or permanently12.Wound healing:Patients with skin ulcers and decreased levels of zinc may benefit from oral zinc supplements12.Diahrrea: Oral zinc supplements can reduce the symptoms of diarrhea in children with low levels of zinc, especially in cases of malnutrition12.",[Zn++].CC([O-])=O.CC([O-])=O,"Zinc has three primary biological roles:catalytic,structural, andregulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately human proteins including enzymes, nuclear factors, and hormones.Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins.In HL- cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-beta, and IL-.There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine --cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to September .Zinc deficiency in humans decreases the activity of serumthymulin(a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper (Th()) cytokines are decreased but T-helper (Th()) cytokines are not affected by zinc deficiency in humans.The change ofTh()toTh()function leads to cell-mediated immune dysfunction. Because IL- production (Th() cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells.In humans, zinc deficiency may lead to the generation of new CD+ T cells, produced in the thymus. In cell culture studies (HUT-, a Th() human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th() cytokine production.In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers. In HL- cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-beta, and IL- cytokines and mRNA. In such cells, zinc was found to induce A, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers.The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels.TargetActionsOrganismUB bradykinin receptorNot AvailableHumansUMethylated-DNA--protein-cysteine methyltransferaseNot AvailableHumansUFructose-bisphosphate aldolase ANot AvailableHumansUElongation factor -alpha Not AvailableHumansUAlpha-enolaseNot AvailableHumansUGlyceraldehyde--phosphate dehydrogenase, testis-specificNot AvailableHumansUNucleoside diphosphate kinase ANot AvailableHumansUProtein disulfide-isomeraseNot AvailableHumansUProtein disulfide-isomerase ANot AvailableHumansUPeroxiredoxin-Not AvailableHumansUPhosphoserine phosphataseNot AvailableHumansUTriosephosphate isomeraseNot AvailableHumansUElongation factor Tu, mitochondrialNot AvailableHumansUEstrogen receptor alphaNot AvailableHumansUInterleukin-Not AvailableHumansUMetallothionein-Not AvailableHumansUCopper chaperone for superoxide dismutaseNot AvailableHumansUHistone deacetylase Not AvailableHumansUHistone deacetylase Not AvailableHumansUDNA--methyladenine glycosylaseNot AvailableHumansUSemenogelin-Not AvailableHumansUSuperoxide dismutase [Cu-Zn]Not AvailableHumansUHistone deacetylase Not AvailableHumansUApoptosis regulatory protein SivaNot AvailableHumansUGlycine receptor subunit alpha-Not AvailableHumansUE ubiquitin-protein ligase MdmNot AvailableHumansUInsulinNot AvailableHumansUUtrophinNot AvailableHumansUAspartoacylaseNot AvailableHumansUProtein S-ANot AvailableHumansUProtein S-ANot AvailableHumansUMatrix metalloproteinase-Not AvailableHumansUTumor protein pNot AvailableHumansUProtein S-ANot AvailableHumansUCellular tumor antigen pNot AvailableHumansUMetallothionein-Not AvailableHumansUProgrammed cell death protein Not AvailableHumansUDAN domain family member Not AvailableHumansUMetallothionein-ANot AvailableHumansUAlpha-B-glycoproteinNot AvailableHumansUAlpha--macroglobulinNot AvailableHumansUAngiotensinogenNot AvailableHumansUAlpha--HS-glycoproteinNot AvailableHumansUSerum amyloid P-componentNot AvailableHumansUApolipoprotein A-INot AvailableHumansUApolipoprotein A-IINot AvailableHumansUApolipoprotein A-IVNot AvailableHumansUApolipoprotein B receptorNot AvailableHumansUApolipoprotein ENot AvailableHumansUApolipoprotein LNot AvailableHumansUComplement Cq subcomponent subunit BNot AvailableHumansUComplement Cq subcomponent subunit CNot AvailableHumansUComplement Cr subcomponentNot AvailableHumansUComplement Cs subcomponentNot AvailableHumansUComplement CNot AvailableHumansUComplement C-BNot AvailableHumansUCb-binding protein alpha chainNot AvailableHumansUCb-binding protein beta chainNot AvailableHumansUComplement CNot AvailableHumansULys--specific deubiquitinase BRCCNot AvailableHumansUComplement component C alpha chainNot AvailableHumansUComplement component C beta chainNot AvailableHumansUComplement component C gamma chainNot AvailableHumansUComplement factor BNot AvailableHumansUComplement factor HNot AvailableHumansUComplement factor INot AvailableHumansUClusterinNot AvailableHumansUCeruloplasminNot AvailableHumansUCarboxypeptidase N catalytic chainNot AvailableHumansUCarboxypeptidase N subunit Not AvailableHumansUDermcidinNot AvailableHumansUDesmoplakinNot AvailableHumansUCoagulation factor XIINot AvailableHumansUCoagulation factor XIII B chainNot AvailableHumansUProthrombinNot AvailableHumansUFicolin-Not AvailableHumansUFibrinogen alpha chainNot AvailableHumansUFibronectinNot AvailableHumansUGelsolinNot AvailableHumansUHemoglobin subunit alphaNot AvailableHumansUHemoglobin subunit betaNot AvailableHumansUHaptoglobin-related proteinNot AvailableHumansUHornerinNot AvailableHumansUInsulin-like growth factor-binding protein complex acid labile subunitNot AvailableHumansUIg alpha- chain C regionNot AvailableHumansUIg mu chain C regionNot AvailableHumansUImmunoglobulin kappa variable -Not AvailableHumansUIg kappa chain V-III region GOLNot AvailableHumansUImmunoglobulin lambda variable -Not AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUInter-alpha-trypsin inhibitor heavy chain HNot AvailableHumansUImmunoglobulin J chainNot AvailableHumansUJunction plakoglobinNot AvailableHumansUPlasma kallikreinNot AvailableHumansUKininogen-Not AvailableHumansUKeratin, type II cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUKeratin, type II cytoskeletal epidermalNot AvailableHumansUKeratin, type II cytoskeletal Not AvailableHumansUKeratin, type II cytoskeletal ANot AvailableHumansUKeratin, type I cytoskeletal Not AvailableHumansUAlpha--acid glycoprotein Not AvailableHumansUN-acetylmuramoyl-L-alanine amidaseNot AvailableHumansUSerum paraoxonase/arylesterase Not AvailableHumansUPregnancy zone proteinNot AvailableHumansUProtein S-ANot AvailableHumansUSelenoprotein PNot AvailableHumansUAlpha--antitrypsinNot AvailableHumansUAlpha--antichymotrypsinNot AvailableHumansUKallistatinNot AvailableHumansUCorticosteroid-binding globulinNot AvailableHumansUHeparin cofactor Not AvailableHumansUSex hormone-binding globulinNot AvailableHumansUSerotransferrinNot AvailableHumansUTransthyretinNot AvailableHumansUVitronectinNot AvailableHumansUAmyloid-like protein Not AvailableHumansUAmyloid-like protein Not AvailableHumansUAmyloid beta A proteinNot AvailableHumansUPoly [ADP-ribose] polymerase Not AvailableHumans",[],"['Acetates', 'Acids, Acyclic', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Alimentary Tract and Metabolism', 'Metal cations', 'Metal divalent cations', 'Minerals', 'Various Alimentary Tract and Metabolism Products', 'Vasoprotectives', 'Zinc Compounds']" +DB01172,Kanamycin,Kanamycinis an aminoglycoside antibiotic agent used in the treatment of various infections caused by susceptible bacteria.,['P0A7S3'],"Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.",NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1O,"Aminoglycosides like kanamycin ""irreversibly"" bind to specific S-subunit proteins and S rRNA. Specifically Kanamycin binds to four nucleotides of S rRNA and a single amino acid of protein S. This interferes with decoding site in the vicinity of nucleotide in S rRNA of S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal RNAinhibitorEnteric bacteria and other eubacteria",[],"['Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antiinfectives for Systemic Use', 'Carbohydrates', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inhibitors', 'Glycosides', 'Intestinal Antiinfectives', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'Ophthalmologicals', 'Protein Synthesis Inhibitors', 'Sensory Organs']" +DB09073,Palbociclib,Palbociclibis an endocrine-based chemotherapeutic agent used in combination with other antineoplastic agents to treat HER2-negative and HR-positive advanced or metastatic breast cancer.,"['P11802', 'Q00534']","Due to its mechanism of action, palbociclib inhibits cell growth and suppresses DNA replication in retinoblastoma tumor suppressor gene (RB) proficient cancer cells. As expected, these RB cells present a significant increase in the proportion of cells in G1 state and the presence of palbociclib produces effective dephosphorylation of RB, reduce proliferation and induce senescence causing cell-cycle arrest.5In vitro studies showed the potential for palbociclib to reduce cellular proliferation of estrogen receptor-positive breast cancer cell lines through the inhibition of the cell-cycle progression from G1 to S phase. In this study, it was demonstrated that the sensitivity of the cells significantly increased with the expression ofRB1andCCND1and low expression ofCDKN2A. As well, palbociclib, combined with antiestrogens, enhancedin vivoantitumor activity in estrogen receptor-positive breast cancer mouse models.3In clinical trials, palbociclib, in combination with letrozole, was shown to significantly increase the progression-free survival (PFS) in patients with metastatic breast cancer without prior endocrine treatment. In the results, the PFS increased from 4.5 to 9.5 months with an overall response rate (ORR) of 24.6%.2",CC(=O)C1=C(C)C2=CN=C(NC3=NC=C(C=C3)N3CCNCC3)N=C2N(C2CCCC2)C1=O,"Palbociclib is a cyclin-dependent kinase / (CDK/) inhibitorthat acts by binding to the ATP pocket with an IC in the range of - nmol/L. It is important to consider that it presents low to absent activity against other kinases.The CDK/ kinase is involved, with coregulatory partner cyclin D, in the G-S transition. Hence, inhibition of this step prevents cell cycle progression in cells in whose this pathway is functioning. This step includes the pathways of the phosphorylation of retinoblastoma protein and the EF family of transcription factors.TargetActionsOrganismACyclin-dependent kinase inhibitorHumansACyclin-dependent kinase inhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cyclin-dependent kinase (CDK) inhibitors', 'Cyclin-Dependent Kinases, antagonists & inhibitors', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OCT1 inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Protein Kinase Inhibitors']" +DB06774,Capsaicin,"Capsaicinis a topical analgesic agent used for the symptomatic relief of neuropathic pain associated with post-herpetic neuralgia, as well as other muscle and joint pain.","['Q8NER1', 'Q99623']","Capsaicin is a TRPV1 receptor agonist. TRPV1 is a trans-membrane receptor-ion channel complex activated by temperatures higher than 43 degrees Celsius, pH lower than 6, and endogenous lipids. When activated by a combination of these factors, the channel can transiently open and initiate depolarization due to the influx of calcium and sodium ions. Because TRPV1 is commonly expressed in A-delta and mostly C fibers, depolarization results in action potentials which send impulses to the brain and spinal cord. These impulses result in capsaicin effects of warming, tingling, itching, stinging, or burning. Capsaicin also causes more persistent activation of these receptors compared to the environmental agonists, resulting in a loss of response to many sensory stimuli, described as ""defunctionalization"". Capsaicin is associated with many enzymatic, cytoskeletal, and osmotic changes, as well as disruption of mitochondrial respiration, impairing nociceptor function for extended periods of time.",COC1=C(O)C=CC(CNC(=O)CCCC\C=C\C(C)C)=C1,"Capsaicin has been shown to reduce the amount of substance P associated with inflammation - however this is not believed to be its main mechanism in the relief of pain. Capsaicin's mechanism of action is attributed to ""defunctionalization"" of nociceptor fibers by inducing a topical hypersensitivity reaction on the skin. This alteration in pain mechanisms is due to many of the following: temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fiber terminals.TargetActionsOrganismATransient receptor potential cation channel subfamily V member agonistregulatorHumansUProhibitin-Not AvailableHumans",[],"['Alkaloids', 'Alkenes', 'Amides', 'Analgesics', 'Anesthetics', 'Anesthetics, Local', 'Antipruritics', 'Basic Lotions and Liniments', 'Benzene Derivatives', 'Capsaicin and Similar Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Lipids', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Peripheral Nervous System Agents', 'Phenols', 'Polyunsaturated Alkamides', 'Sensory System Agents', 'Solanaceous Alkaloids', 'Topical Products for Joint and Muscular Pain', 'TRPV1 Channel Agonists']" +DB08828,Vismodegib,Vismodegibis a hedgehog pathway inhibitor used to treat patients with locally advanced or metastatic basal cell carcinoma.,['Q99835'],"Vismodegib selectively binds to and inhibits the transmembrane protein smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway. Following 7 days of 150 mg once-daily dosing, the use of vismodegib was not associated with a clinically significant QT interval prolongation.6Vismodegib can cause embryo-fetal death or severe birth defects, as well as severe cutaneous adverse reactions and musculoskeletal adverse reactions. In pediatric patients given vismodegib, premature fusion of the epiphyses has been reported.6",CS(=O)(=O)C1=CC(Cl)=C(C=C1)C(=O)NC1=CC=C(Cl)C(=C1)C1=CC=CC=N1,"During embryogenesis, the Hedgehog signaling pathway plays an important role in cell growth, differentiation apoptosis and self-renewal. After this developmental stage, the Hedgehog signaling pathway is silenced in all cells and tissues, except for hair, skin and stem cells. Mutations on elements of the Hedgehog signaling pathway may result in uncontrolled proliferation of basal skin cells, and dysregulated or aberrant Hedgehog signaling has been associated with the pathogenesis of basal cell carcinoma. Therefore, drugs that target and block this pathway, such as vismodegib, may be used to treat this condition. Vismodegib binds to and inhibits the transmembrane protein smoothened homologue (SMO), a protein that leads to the activation and nuclear translocation of several factors involved in the Hedgehog signaling pathway, inhibiting the activation of downstream Hedgehog target genes.,TargetActionsOrganismASmoothened homologantagonistinhibitorHumans",[],"['Amides', 'Amines', 'Aniline Compounds', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hedgehog Pathway Inhibitor', 'Hedgehog pathway inhibitors', 'P-glycoprotein substrates', 'Smoothened Receptor Antagonists']" +DB00550,Propylthiouracil,Propylthiouracilis a thiourea antithyroid agent used to treat hyperthyroidism.,['P07202'],"Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole.",CCCC1=CC(=O)NC(=S)N1,"Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the and/or positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T) and tri-iodothyronine (T), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.TargetActionsOrganismAThyroid peroxidaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Antimetabolites', 'Antithyroid agents', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Noxae', 'Pyrimidines', 'Pyrimidinones', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thiouracil', 'Thiouracils', 'Thyroid Hormone Synthesis Inhibitor', 'Thyroid Hormone Synthesis Inhibitors', 'Thyroid Products', 'Toxic Actions']" +DB01582,Sulfamethazine,"Sulfamethazineis an antibacterial agent used in the treatment of various bacterial infections, such as bronchitis, prostatitis, and urinary tract infections.",['P0AC13'],Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA.,CC1=CC(C)=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=N1,"Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.TargetActionsOrganismADihydropteroate synthaseinhibitorEscherichia coli (strain K)",[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Benzene Derivatives', 'Benzenesulfonamides', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Short-Acting Antibacterial Sulfonamides', 'Sulfanilamides', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds']" +DB00398,Sorafenib,"Sorafenibis a kinase inhibitor used to treat unresectable liver carcinoma, advanced renal carcinoma, and differentiated thyroid carcinoma.","['P15056', 'P04049', 'P35916', 'P35968', 'P17948', 'P36888', 'P09619', 'P10721', 'P11362', 'P07949']","Sorafenib decreases tumour cell proliferationin vitro. It attenuated tumour growth of human tumour xenografts in immunocompromised mice, reduced tumour angiogenesis, and increased tumour apoptosis in models of hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma.1,5Some studies suggest that sorafenib induces apoptosis in several tumour cell lines, although this effect is inconsistent across cell lines.1Antiviral effects of sorafenib have been documented, as it was shown to inhibit hepatitis C viral replicationin vitro.1",CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1,"Kinases are involved in tumour cell signalling, proliferation, angiogenesis, and apoptosis.,Sorafenib inhibits multiple intracellular serine/threonine kinases in the Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway. Intracellular Raf serine/threonine kinase isoforms inhibited by sorafenib include Raf- (or C-Raf), wild-type B-Raf, and mutant B-Raf. Sorafenib inhibits cell surface tyrosine kinase receptors such as KIT, FMS-like tyrosine kinase (FLT-), RET, RET/PTC, vascular endothelial growth factor receptor- (VEGFR-), VEGFR-, VEGFR-, and platelet-derived growth factor receptor-β (PDGFR-β).,,,Sorafenib is thought to exhibit a dual mechanism of action: it blocks tumour proliferation and growth by inhibiting the RAF/MEK/extracellular signal-regulated kinase (ERK) pathway on tumour cells, and reduces tumour angiogenesis by inhibiting VEGFR and PDGFR signalling in tumour vasculature.,TargetActionsOrganismASerine/threonine-protein kinase B-rafinhibitorHumansARAF proto-oncogene serine/threonine-protein kinaseinhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAReceptor-type tyrosine-protein kinase FLTinhibitorHumansAPlatelet-derived growth factor receptor betainhibitorHumansAMast/stem cell growth factor receptor KitantagonistHumansAFibroblast growth factor receptor inhibitorHumansAProto-oncogene tyrosine-protein kinase receptor RetinhibitorHumans",[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nicotinic Acids', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Phenylurea Compounds', 'Potential QTc-Prolonging Agents', 'Protein Kinase Inhibitors', 'Pyridines', 'QTc Prolonging Agents', 'Tyrosine Kinase Inhibitors', 'UGT1A1 Inhibitors', 'UGT1A9 Inhibitors', 'UGT1A9 Substrates', 'UGT1A9 Substrates with a Narrow Therapeutic Index']" +DB01174,Phenobarbital,"Phenobarbitalis a long-lasting barbiturate and anticonvulsant used in the treatment of all types of seizures, except for absent seizures.","['P14867', 'P43681', 'P36544', 'P42262', 'Q13002', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'O75469']","Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal).",CCC1(C(=O)NC(=O)NC1=O)C1=CC=CC=C1,"Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumansUNMDA receptorantagonistHumansUNuclear receptor subfamily group I member activatorHumans",['Sedation'],"['Anticholinergic Agents', 'Anticonvulsants', 'Barbiturates', 'Barbiturates and Derivatives', 'BSEP/ABCB11 inducers', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strong)', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers (strong)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers (weak)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strong)', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Enzyme Inducing Antiepileptic Drugs', 'Excitatory Amino Acid Agents', 'Excitatory Amino Acid Antagonists', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Methemoglobinemia Associated Agents', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Phenobarbital and similars', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones', 'UGT1A1 Inducers', 'UGT2B7 inducers']" +DB00951,Isoniazid,Isoniazidis an antibiotic used to treat mycobacterial infections; most commonly use in combination with other antimycobacterial agents for the treatment of active or latent tuberculosis.,"['P9WIE5', 'P9WGR1', 'P10632', 'P05177', 'P08684', 'P33261', 'P9WNX1']","Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specificallyM. tuberculosis,M. bovisandM. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal when mycobacteria grow rapidly and bacteriostatic when they grow slowly.",NNC(=O)C1=CC=NC=C1,"Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellularMycobacterium tuberculosisorganisms. Specifically isoniazid inhibits InhA, the enoyl reductase fromMycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.TargetActionsOrganismACatalase-peroxidaseother/unknownMycobacterium tuberculosisAEnoyl-[acyl-carrier-protein] reductase [NADH]adductMycobacterium tuberculosisUCytochrome P CNot AvailableHumansUCytochrome P ANot AvailableHumansUCytochrome P ANot AvailableHumansUCytochrome P CNot AvailableHumansUDihydrofolate reductaseNot AvailableMycobacterium tuberculosis",[],"['Agents Causing Muscle Toxicity', 'Agents that reduce seizure threshold', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (moderate)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Fatty Acid Synthesis Inhibitors', 'Hepatotoxic Agents', 'Hydrazides', 'Hydrazines', 'Hyperglycemia-Associated Agents', 'Hypolipidemic Agents', 'Isonicotinic Acids', 'Pyridines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00605,Sulindac,"Sulindacis an NSAID used to treat osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute subacromial bursitis or supraspinatus tendinitis, and acute gouty arthritis.","['P35354', 'P23219', 'P15121', 'P27361', 'Q03181', 'Q9Y5Y4', 'O60218']","Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.",CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(C=C1)S(C)=O,"Sulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both COX- and COX- which leads to the inhibition of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumansUAldose reductaseinhibitorHumansUMitogen-activated protein kinase inhibitorHumansUPeroxisome proliferator-activated receptor deltanegative modulatorHumansUProstaglandin D receptor antagonistHumansUAldo-keto reductase family member BinhibitorHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Indenes', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Sensory System Agents']" +DB00730,Thiabendazole,"Thiabendazoleis a benzimidazole used in the treatment of strongyloides, cutaneous larva migrans, visceral larva migrans, and trichinosis infections.",['P00363'],"Thiabendazole is a fungicide and parasiticide. Thiabendazole is also a chelating agent, which means that it is used medicinally to bind metals in cases of metal poisoning, such as lead poisoning, mercury poisoning or antimony poisoning. Thiabendazole is vermicidal and/or vermifugal againstAscaris lumbricoides(""common roundworm""),Strongyloides stercoralis(threadworm),Necator americanus,Ancylostoma duodenale(hookworm),Trichuris trichiura(whipworm),Ancylostoma braziliense(dog and cat hookworm),Toxocara canis,Toxocara cati(ascarids), andEnterobius vermicularis(pinworm). Thiabendazole also suppresses egg and/or larval production and may inhibit the subsequent development of those eggs or larvae which are passed in the feces.",N1C2=CC=CC=C2N=C1C1=CSC=N1,"The precise mode of action of thiabendazole on the parasite is unknown, but it most likely inhibits the helminth-specific enzyme fumarate reductase.TargetActionsOrganismAFumarate reductase flavoprotein subunitinhibitorEscherichia coli (strain K)",[],"['Anthelmintics', 'Anti-Infective Agents', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Antihelminthic', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Benzimidazole Derivatives', 'Benzimidazoles', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Imidazole and Triazole Derivatives', 'Sulfur Compounds', 'Thiazoles']" +DB01168,Procarbazine,Procarbazineis an antineoplastic agent indicated for the treatment of stage III and stage IV Hodgkin's disease in combination with other chemotherapeutic agents.,"['P21397', 'P27338']","Procarbazine is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Procarbazine is cell-phase specific for the S phase of cell division.",CNNCC1=CC=C(C=C1)C(=O)NC(C)C,"The precise mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA.TargetActionsOrganismAMonoamine oxidaseinhibitorHumansADNAcross-linking/alkylationHumans",[],"['Acids, Carbocyclic', 'Agents Causing Muscle Toxicity', 'Alkylating Activity', 'Alkylating Drugs', 'Amides', 'Antidepressive Agents', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Depressants', 'Immunosuppressive Agents', 'Methylhydrazines', 'Monoamine Oxidase Inhibitors', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB00307,Bexarotene,Bexaroteneis a retinoid drug used for cutaneous manifestations of T-cell lymphoma in patients who have not responded well to previous systemic therapy.,"['P19793', 'P28702', 'P48443']","Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growthin vitroof some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regressionin vivoin some animal models.",CC1=CC2=C(C=C1C(=C)C1=CC=C(C=C1)C(O)=O)C(C)(C)CCC2(C)C,"Bexarotene selectively binds with and activates retinoid X receptor subtypes. There are three subtypes in total: RXRα, RXRβ, RXRγ. The exact mechanism of action of bexarotene in the treatment of CTCL is unknown but the drug has activity in all clinical stages of CTCL.TargetActionsOrganismARetinoic acid receptor RXR-alphaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor RXR-gammaagonistHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Compounds used in a research, industrial, or household setting', 'Cyclohexanes', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Naphthalenes', 'Retinoids', 'Retinoids for cancer treatment', 'Tetrahydronaphthalenes']" +DB00347,Trimethadione,Trimethadioneis an anticonvulsant agent indicated for the control of treatment-refractory petit mal seizures.,['O43497'],Paramethadione and trimethadione are anticonvulsants indicated in the control of absence (petit mal) seizures that are refractory to treatment with other medications. Dione anticonvulsants are used in the treatment of epilepsy. They act on the central nervous system (CNS) to reduce the number of seizures.,CN1C(=O)OC(C)(C)C1=O,"Dione anticonvulsants reduce T-type calcium currents in thalamic neurons, including thalamic relay neurons. It does so via the inhibition of voltage dependent T-type calcium channels. This raises the threshold for repetitive activity in the thalamus, and inhibits corticothalamic transmission. Thus, the abnormal thalamocortical rhythmicity, which is thought to underlie the -Hz spike-and-wave discharge seen on electroencephalogram(EEG) with absence seizures, is dampened.TargetActionsOrganismAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumans",[],"['Agents causing hyperkalemia', 'Anti-epileptic Agent', 'Antiarrhythmic agents', 'Anticonvulsants', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Nervous System', 'Oxazoles', 'Oxazolidine Derivatives', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB01033,Mercaptopurine,Mercaptopurineis an antineoplastic agent used to treat acute lymphocytic leukemia.,"['P00492', 'Q06203', 'P20839', 'P12268']",Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death.,S=C1N=CNC2=C1NC=N2,"Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). TIMP inhibits several reactions that involve inosinic acid (IMP), such as the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). Upon methylation, TIMP forms -methylthioinosinate (MTIMP) which inhibits glutamine--phosphoribosylpyrophosphate amidotransferase in addition to TIMP. Glutamine--phosphoribosylpyrophosphate amidotransferase is the first enzyme unique to thede novopathway for purine ribonucleotide synthesis. According to experimental findings using radiolabeled mercaptopurine, mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. In comparison, some mercaptopurine may be converted to nucleotide derivatives of -thioguanine (-TG) via actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase that convert TIMP to thioguanylic acid (TGMP).TargetActionsOrganismAHypoxanthine-guanine phosphoribosyltransferaseinhibitorHumansUAmidophosphoribosyltransferaseinhibitorHumansUInosine-'-monophosphate dehydrogenaseinhibitorHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Drugs for Obstructive Airway Diseases', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleoside Metabolic Inhibitor', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index', 'Purine Analogues', 'Purines', 'Sulfhydryl Compounds', 'Sulfur Compounds', 'Thiopurine Analogs', 'Toxic Actions', 'Xanthine derivatives']" +DB00158,Folic acid,Folic acidis a nutrient used to treat megaloblastic anemia and is found in many supplements.,"['P41439', 'P14207', 'P15328']","Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such asMethotrexateas they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF.In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.",NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1,"Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.TargetActionsOrganismUFolate receptor gammabinderHumansUFolate receptor betabinderHumansUFolate receptor alphaNot AvailableHumans",['Nutritional supplementation'],"['Antianemic Preparations', 'Autacoids', 'BCRP/ABCG2 Substrates', 'Biological Factors', 'Diagnostic Agents', 'Diet, Food, and Nutrition', 'Dietary Supplements', 'Drugs that are Mainly Renally Excreted', 'Folic Acid and Derivatives', 'Food', 'Growth Substances', 'Hematinics', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Micronutrients', 'OAT1/SLC22A6 inhibitors', 'Pteridines', 'Pterins', 'Supplements', 'Vitamin B Complex', 'Vitamin B12 and Folic Acid', 'Vitamins']" +DB00523,Alitretinoin,Alitretinoinis a vitamin A derivative used to treat Kaposi's sarcoma and used off label to treat chronic hand eczema and psoriasis.,"['P10276', 'P19793', 'P10826', 'P28702', 'P13631', 'P48443', 'P17936', 'Q15238', 'Q6V0L0']",Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cellsin vitro.,C\C(\C=C\C1=C(C)CCCC1(C)C)=C\C=C\C(\C)=C\C(O)=O,"Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells.TargetActionsOrganismARetinoic acid receptor alphaagonistHumansARetinoic acid receptor RXR-alphaagonistHumansARetinoic acid receptor betaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor gammaagonistHumansARetinoic acid receptor RXR-gammaagonistHumansUInsulin-like growth factor-binding protein Not AvailableHumansUPregnancy-specific beta--glycoprotein Not AvailableHumansUCytochrome P CNot AvailableHumans",[],"['Agents for Dermatitis, Excluding Corticosteroids', 'Alkenes', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Biological Factors', 'Carotenoids', 'Cyclohexanes', 'Cyclohexenes', 'Cycloparaffins', 'Dermatologicals', 'Diterpenes', 'Hydrocarbons, Acyclic', 'Misc. Skin and Mucous Membrane Agents', 'P-glycoprotein substrates', 'Pigments, Biological', 'Polyenes', 'Retinoids', 'Retinoids for cancer treatment', 'Terpenes', 'Vitamin A', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB11155,Triclocarban,Triclocarbanis an antibacterial agent used in liquid soaps and body washes.,['Q6GI75'],"The antimicrobial mechanism underlying the bacteriostatic and bactericidal effects of triclocarban is believed to be an unspecific adsorption to cell membranes and interruption of their function. As a result, the growth of gram-positive as well as gram-negative bacteria is inhibited15.",ClC1=CC=C(NC(=O)NC2=CC(Cl)=C(Cl)C=C2)C=C1,"Triclocarban is a triclosan analog with an antibacterial activity. Triclocarban exerts its effect by inhibiting the activity ofenoyl-(acyl-carrier protein) (ACP) reductase, which is ubiquitously distributed in bacteria, fungi and various plants. ACP reductase catalyzes the last step in each cycle of fatty acid elongation in the type II fatty acid synthase systems. As a result, this agent interrupts cell membrane synthesis and leads to bacterial growth inhibition.TargetActionsOrganismAEnoyl-[acyl-carrier-protein] reductase [NADPH] FabIantagonistStaphylococcus aureus (strain MRSA)",[],"['Amides', 'Amines', 'Anilides', 'Aniline Compounds', 'Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Benzene Derivatives', 'Environmental Pollutants', 'Miscellaneous Local Anti-infectives', 'Phenylurea Compounds', 'Toxic Actions', 'Water Pollutants', 'Water Pollutants, Chemical']" +DB09256,Tegafur,Tegafuris an antineoplastic agent used in combination with other anticancer medications to treat advanced gastric and colorectal cancers.,['P04818'],"Tegafur is an antineoplastic agent that belongs in the class of pyrimidine analogues. It interferes with the 2'-deoxythymidylate (DTMP) synthesis in the pyrimidine pathway, resulting in inhibition of DNA synthesis4. In a phase III trial investigating the clinical efficacy of S-1 (tegafur/gimeracil/oteracil) in patients with advanced or recurrent gastric cancer, treatment resulted in a high response rate and was associated with a longer overall survival and longer progression-free survival rate when used in combination with cisplatin1. In a meta analysis, triple combination therapy consisting of tegafur, gimeracil and oteracil showed longer survival times and well tolerance in patients with advanced gastric cancer2. Tegafur and its active metabolites are potent myleosuppressive agents5.",FC1=CN(C2CCCO2)C(=O)NC1=O,"The transformation of '-deoxyurindylate (dUMP) to '-deoxythymidylate (dTMP) is essential in driving the synthesis of DNA and purines in cells. Thymidylate synthase catalyzes the conversion of dUMP to dTMP, which is a precursor of thymidine triphosphate (TTP), one of the four deoxyribonucleotides required for DNA synthesis. After administration into the body, tegafur is converted into the active antineoplastic metabolite, fluorouracil (-FU). In tumour cells, -FU undergoes phosphorylation to form the active anabolites, including -fluorodeoxyuridine monophosphate (FdUMP). FdUMP and reduced folate are bound to thymidylate synthase leading to formation of a ternary complex which inhibits DNA synthesis. In addition, -fluorouridine-triphosphate (FUTP) is incorporated into RNA causing disruption of RNA functions.TargetActionsOrganismAThymidylate synthaseinhibitorHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fluoropyrimidines', 'Fluorouracil and prodrugs', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Pyrimidine Analogues', 'Pyrimidines', 'Pyrimidinones', 'Thyroxine-binding globulin inducers', 'Toxic Actions']" +DB00400,Griseofulvin,Griseofulvinis an antifungal agent used to treat a variety of superficial tinea infections and fungal infections of the fingernails and toes.,"['Q5UBX3', 'Q99456']","Griseofulvin is a mycotoxic metabolic product ofPenicillium spp.It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis.",COC1=CC(OC)=C(Cl)C2=C1C(=O)[C@]1(O2)[C@H](C)CC(=O)C=C1OC,"Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.TargetActionsOrganismATubulin beta chaininhibitorTrichophyton rubrumUKeratin, type I cytoskeletal other/unknownHumans",[],"['Anti-Infective Agents', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Systemic Use', 'Antifungals for Topical Use', 'Benzofurans', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Decreased Mitosis', 'Dermatologicals', 'Heterocyclic Compounds, Fused-Ring', 'Microtubule Inhibition', 'Tubulin Inhibiting Agent']" +DB00811,Ribavirin,Ribavirinis a guanosine nucleoside used to treat some forms of Hepatitis C.,"['P20839', 'P26676', 'P12823', 'P12268', 'P16502']","Ribavirin mediates direct antiviral activity against a number of DNA and RNA viruses by increasing the mutation frequency in the genomes of several RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to its resemblence to building blocks of the RNA molecules.",NC(=O)C1=NN(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O,"Ribavirin is reported to have several mechanism of actions that lead to inhibition of viral RNA and protein synthesis. +After activation by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is the predominant metabolite which directly inhibits viral mRNA polymerase by binding to the nucleotide binding site of the enzyme. This prevents the binding of the correct nucleotides, leading to a reduction in viral replication or to the production of defective virions. RTP also demonstrates an inhibitory action on viral mRNA guanylyltransferase and mRNA ′-O-methyltransferase of dengue virus. Inhibition of these enzymes disrupts the posttranslational capping of the ′ end of viral mRNA through ribavirin being incorporated at the ′ end in place of guanosine and preventing the cap methylation step.Inhibition of host inosine monophosphate dehydrogenase (IMPDH) and subsequent depletion of GTP pool is proposed to be another mechanism of action of ribavirin. IMPDH catalyzes the rate-limiting step where inosine ′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphoshpate (GTP). Ribavirin monophosphate mimics inosine ′-monophosphate and acts as a competitive inhibitor of IMPDH. Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes.Ribavirin acts as a mutagen in the target virus to cause an 'error catastrophe' due to increased viral mutations. RTP pairs with cytidine triphosphate or uridine triphosphate with equal efficiency and to block HCV RNA elongation. It causes premature termination of nascent HCV RNA and increases mutagenesis by producing defective virions.Ribavirin also exerts an immunomodulatory action of the host to the virus by shifting a Th response in favor of a Th phenotype. Th response and production of type cytokines such as IL-, IL-, and IL- stimulates the humoral response which enhances immunity toward the virus. Ribavirin enhanced induction of interferon-related genes, including the interferon-α receptor, and down-regulation of genes involved in interferon inhibition, apoptosis, and hepatic stellate cell activation in vitro.TargetActionsOrganismAInosine-'-monophosphate dehydrogenase inhibitorHumansARNA-directed RNA polymerase LantagonistHPIV-AGenome polyproteininhibitorDENV-UInosine-'-monophosphate dehydrogenase Not AvailableHumansURNA-directed RNA polymerase catalytic subunitinhibitorInfluenza A virus (strain A/Beijing// HN)",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Noxae', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Analog Antiviral', 'Nucleosides', 'Nucleosides and Nucleotides', 'Ribonucleosides', 'Toxic Actions', 'Treatments for Hepatitis C']" +DB00564,Carbamazepine,Carbamazepineis an anticonvulsant used to treat various types of seizures and pain resulting from trigeminal neuralgia.,"['P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'P43681', 'O75469']","General effectsCarbamazepine treats seizures and the symptoms of trigeminal neuralgia by inhibiting sodium channels. In bipolar 1 disorder, carbamazepine has been found to decrease mania symptoms in a clinically significant manner according to the Young Mania Rating Scale (YMRS).16Carbamazepine has a narrow therapeutic index.3A note on genetic variation and carbamazepine useIn studies of Han Chinese ancestry patients, a pronounced association between the HLA-B*1502 genotype and Steven Johnson syndrome and/or toxic epidermal necrolysis (SJS/TEN) resulting from carbamazepine use was observed.7",NC(=O)N1C2=CC=CC=C2C=CC2=CC=CC=C12,"Carbamazepine's mechanism of action is not fully elucidated and is widely debated.,One major hypothesis is that carbamazepine inhibits sodium channel firing, treating seizure activity. Animal research studies have demonstrated that carbamazepine exerts its effects by lowering polysynaptic nerve response and inhibiting post-tetanic potentiation. In both cats and rats, carbamazepine was shown to decrease pain caused by infraorbital nerve stimulation. A decrease in the action potential in the nucleus ventralis of the thalamus in the brain and inhibition of the lingual mandibular reflex were observed in other studies after carbamazepine use. Carbamazepine causes the above effects by binding to voltage-dependent sodium channels and preventing action potentials, which normally lead to stimulatory effects on nerves.,In bipolar disorder, carbamazepine is thought to increase dopamine turnover and increase GABA transmission, treating manic and depressive symptoms.A common issue that has arisen is resistance to this drug in up to % of epileptic patients, which may occur to altered metabolism in patients with variant genotypes.A potential therapeutic target to combat carbamazepine resistance has recently been identified as the EPHX gene promoter, potentially conferring resistance to carbamazepine through methylation.TargetActionsOrganismAVoltage-gated sodium channel alpha subunitinhibitorHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNuclear receptor subfamily group I member activatorHumans",[],"['Analgesics', 'Analgesics, Non-Narcotic', 'Anticonvulsants', 'Antimanic Agents', 'Carboxamide Derivatives', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strong)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strong)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Inducers (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Dibenzazepines', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inducing Antiepileptic Drugs', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Inducers of Drug Clearance', 'Membrane Transport Modulators', 'Miscellaneous Anticonvulsants', 'Mood Stabilizer', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Psychotropic Drugs', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sodium Channel Blockers', 'Thyroxine-binding globulin substrates', 'UGT1A1 Inducers', 'UGT1A6 inducer', 'UGT2B7 substrates', 'UGT2B7 Substrates with a Narrow Therapeutic Index']" +DB00205,Pyrimethamine,Pyrimethamineis an antiparasitic drug used in the prevention and treatment of toxoplasmosis and malaria.,"['P00374', 'P13922', 'P07686']","Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.",CCC1=C(C(N)=NC(N)=N1)C1=CC=C(Cl)C=C1,"Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.TargetActionsOrganismADihydrofolate reductaseinhibitorHumansABifunctional dihydrofolate reductase-thymidylate synthaseinhibitorPlasmodium falciparum (isolate K / Thailand)UBeta-hexosaminidase subunit betaNot AvailableHumans",[],"['Anti-Infective Agents', 'Antibiotics for Pneumocystis Pneumonia', 'Antimalarial diaminopyrimidines', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Folic Acid Antagonists', 'MATE 1 Inhibitors', 'MATE 2 Inhibitors', 'MATE inhibitors', 'Pyrimidines']" +DB00267,Cefmenoxime,Cefmenoxime is a novel broad-spectrum and third-generation cephalosporin antibiotic that is typically used in the treatment of female gynecologic and obstetric infections. It is reported to exhibit high activity against a wide variety of gram-positive and gram-negative bacteria.,"['P0AD68', 'Q8XJ01']",Cefmenoxime is a semisynthetic beta-lactam cephalosporin antibiotic with activity similar to that of cefotaxime. It has broad spectrum activity against Gram positive and Gram negative bacteria.,[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O,"The bactericidal activity of cefmenoxime results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefmenoxime is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.TargetActionsOrganismAPeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Ophthalmologicals', 'Otologicals', 'Sensory Organs', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00617,Paramethadione,"Paramethadione is an anticonvulsant in the oxazolidinedione class. It is associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.",['Q9P0X4'],"Paramethadione is an oxazolidinedione anticonvulsant similar to trimethadione that acts on the central nervous system (CNS) to reduce the number of absence seizures (often seen in epileptics). Absence seizures involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Paramethadione acts on thalamic neurons in the thalamic reticular nucleus (which studies have shown to be associated with absence seizures, von Krosigk et al., 1993).",CCC1(C)OC(=O)N(C)C1=O,Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the -Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.TargetActionsOrganismAVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumans,[],"['Anticonvulsants', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Nervous System', 'Oxazolidine Derivatives']" +DB01577,Metamfetamine,Metamfetamineis a sympathomimetic agent used in the treatment of attention deficit hyperactivity disorder (ADHD) and exogenous obesity.,"['Q01959', 'P31645', 'P23975', 'Q05940', 'P54219', 'Q96RJ0', 'P08913', 'P18089', 'P18825', 'P21397', 'P27338']","Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.",CN[C@@H](C)CC1=CC=CC=C1,"Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.TargetActionsOrganismASodium-dependent dopamine transporternegative modulatorHumansASodium-dependent serotonin transporternegative modulatorHumansASodium-dependent noradrenaline transporternegative modulatorHumansASynaptic vesicular amine transporterinhibitorHumansAChromaffin granule amine transporterinhibitorHumansATrace amine-associated receptor agonistHumansAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-C adrenergic receptoragonistHumansAAmine oxidase [flavin-containing] AinhibitorHumansAAmine oxidase [flavin-containing] BinhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Amphetamine Anorectic', 'Amphetamines', 'Antidepressive Agents', 'Appetite Suppression', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Centrally Acting Sympathomimetics', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Ethylamines', 'Increased Sympathetic Activity', 'Membrane Transport Modulators', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetics']" +DB00987,Cytarabine,"Cytarabineis a pyrimidine nucleoside analogue used to treat acute non-lymphocytic leukemia, lymphocytic leukemia, and the blast phase of chronic myelocytic leukemia.",['P06746'],"Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the ""S"" phase (of the cell cycle), stopping normal development and division. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle.",NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O,"Cytarabine acts through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G phase to the S-phase. Although the mechanism of action is not completely understood, it appears that cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of cytarabine into both DNA and RNA has also been reported.TargetActionsOrganismADNA polymerase betainhibitorHumansADNAcross-linking/alkylationHumans",[],"['Agents Causing Muscle Toxicity', 'Anti-Infective Agents', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Arabinonucleosides', 'Cardiotoxic antineoplastic agents', 'Cytidine Deaminase Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Immunologic Factors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'OCT1 substrates', 'Pyrimidine Analogues', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Toxic Actions']" +DB00694,Daunorubicin,Daunorubicinis an anthracycline aminoglycoside used to induce remission of nonlymphocytic leukemia and acute lymphocytic leukemia.,"['P11388', 'Q02880']","Daunorubicin is an anthracycline antibiotic and antineoplastic agent.5It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over time.",COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(C)=O)C(O)=C1C2=O,"Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.TargetActionsOrganismADNAintercalationHumansADNA topoisomerase -alphainhibitorHumansADNA topoisomerase -betainhibitorHumans",[],"['Anthracycline Topoisomerase Inhibitor', 'Anthracyclines', 'Anthracyclines and Related Substances', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Cytotoxic Antibiotics and Related Substances', 'Enzyme Inhibitors', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Naphthacenes', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00321,Amitriptyline,"Amitriptylineis a tricyclic antidepressant indicated in the treatment of depressive illness, either endogenous or psychotic, and to relieve depression associated anxiety.","['P23975', 'P31645', 'P28223', 'P08908', 'P41143', 'P41145', 'P04629', 'Q16620', 'P35348', 'P25100', 'P08913', 'P35367', 'O43526', 'Q09470', 'P25021', 'Q9H3N8', 'Q99720', 'P28335', 'P35368', 'P34969', 'P28221', 'P35372', 'P28222', 'P50406', 'O43525', 'P08909', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'Q12809', 'Q9H252', 'Q9NS40']","Effects in pain and depressionAmitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative propertiesLabel. +Clinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed with post-herpetic neuralgia and 3/4 of patients diagnosed with diabetic neuropathic pain, and neurogenic pain syndromes that are frequently unresponsive to narcotic analgesics. Amitriptyline has also shown efficacy in diverse groups of patients with chronic non-malignant pain. There have also been some studies showing efficacy in managing fibromyalgia (an off-label use of this drug)5,8.Cardiovascular and Anticholinergic EffectsAmitriptyline has strong anticholinergic properties and may cause ECG changes and quinidine-like effects on the heart13. Amitriptyline may inhibit ion channels, which are necessary for cardiac repolarization (hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, amitriptyline may increase the risk for cardiac arrhythmiaLabel. Orthostatic hypotension and tachycardia can be a problem in elderly patients receiving this drug at normal doses for depression. There is evidence in the literature that these effects may occur, rarely, at the lower dosages utilized in the treatment of pain. As with any other tricyclic antidepressant agent, increased glucose levels can occur with amitriptyline6.Effects on seizure thresholdThis drug also decreases the convulsive threshold and causes alterations in EEG and sleep patterns13.",CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12,"The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brainLabel,. These amines are important in regulating mood. The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects. This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms.Whether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor AinhibitorinducerHumansUDelta-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumansUHigh affinity nerve growth factor receptoragonistactivatorHumansUBDNF/NT- growth factors receptoragonistHumansNAlpha-A adrenergic receptorantagonistinhibitorHumansNAlpha-D adrenergic receptorantagonistHumansNAlpha-A adrenergic receptorantagonistagonistHumansNHistamine H receptorantagonistHumansNPotassium voltage-gated channel subfamily KQT member inhibitorHumansNPotassium voltage-gated channel subfamily A member inhibitorHumansUHistamine H receptorblockerHumansUHistamine H receptorbinderHumansUSigma non-opioid intracellular receptor agonistHumansU-hydroxytryptamine receptor CantagonistHumansUAlpha-B adrenergic receptorantagonistHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor DbinderHumansUMu-type opioid receptorbinderHumansU-hydroxytryptamine receptor BbinderHumansU-hydroxytryptamine receptor antagonistHumansUPotassium voltage-gated channel subfamily KQT member inhibitorHumansU-hydroxytryptamine receptor CantagonistRatUMuscarinic acetylcholine receptorligandHumansUHERG human cardiac K+ channelblockerHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tertiary amine tricyclic antidepressants', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors', 'UGT1A1 Inhibitors', 'UGT1A4 substrates']" +DB00783,Estradiol,"Estradiolis an estrogenic steroid used to treat vasomotor symptoms of vulvar and vaginal atrophy in menopause, hypoestrogenism, prevention of postmenopausal osteoporosis, treatment of breast cancer, and advanced androgen-dependent carcinoma of the prostate.","['P03372', 'Q92731', 'O75469', 'P43681', 'Q99527', 'P00846', 'Q14457']","Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia).18,19,20Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption18,35and may have beneficial effects on the plasma lipid profile.19,34Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland.27A note on hyper-coagulable state, cardiovascular health, and blood pressureEstradiol may cause an increased risk of cardiovascular disease, DVT, and stroke, and its use should be avoided in patients at high risk of these conditions.35Estrogen induces a hyper-coagulable state, which is also associated with both estrogen-containing oral contraceptive (OC) use and pregnancy. Although estrogen causes an increase in levels of plasma renin and angiotensin. Estrogen-induced increases in angiotensin, causing sodium retention, which is likely to be the mechanism causing hypertension after oral contraceptive treatment.18",[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3,"Estrogen is found in the the breast, uterine, ovarian, skin, prostate, bone, fat, and brain tissues. The main source of estrogen in adult women during the reproductive period of life is the ovarian follicle, which secretes to mcg of estradiol each day. After menopause, however, the majority of endogenous estrogen is produced by transformation of androstenedione (which is secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women.Estradiol, however, is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, the higher estrone concentration in postmenopausal population, can cause various undesirable effects. These effects may include hot flashes, chills, vaginal dryness, mood swings, irregular menstruation, and chills, in addition to sleep problems.Estradiol workings by binding to subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). It also exerts potent agonism of G Protein-coupled estrogen receptor (GPER), which is recognized an important regulator of this drug's rapid effects. Once the estrogen receptor has bound to its ligand, it enters the nucleus of the target cell, regulating gene transcription and formation of of messenger RNA. This mRNA makes contact with ribosomes producing specific proteins that express the effect of estradiol upon the target cell. Agonism of estrogen receptors increases pro-estrogenic effects, leading to the relief of vasomotor and urogenital symptoms of a postmenopausal or low estradiol state.,,TargetActionsOrganismAEstrogen receptor alphaagonistHumansAEstrogen receptor betaagonistHumansUNuclear receptor subfamily group I member binderHumansUNeuronal acetylcholine receptor subunit alpha-binderHumansUG-protein coupled estrogen receptor binderHumansUATP synthase subunit ainhibitorHumansUBeclin-binderHumans","['Contraception', 'Hormone Replacement Therapy', 'Palliative Treatment']","['Adrenal Cortex Hormones', 'Androgens and Estrogens', 'Anti-Gonadotropin-Releasing Hormones', 'Antiandrogens and Estrogens', 'BCRP/ABCG2 Inhibitors', 'COMT Substrates', 'Contraceptive Agents, Female', 'Contraceptives, Oral', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Estradiol Congeners', 'Estradiol, agonists', 'Estranes', 'Estrenes', 'Estrogen Contraceptives', 'Estrogens', 'Estrogens, agonists', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Hypothalamic Hormones', 'Intravaginal Contraceptives', 'Natural and Semisynthetic Estrogens, Plain', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein substrates', 'Pituitary and Hypothalamic Hormones and Analogues', 'Progestogens and Estrogens, Sequential Preparations', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroxine-binding globulin inducers', 'UGT1A1 Substrates']" +DB00438,Ceftazidime,"Ceftazidimeis an injected broad-spectrum third-generation cephalosporin beta-lactam antibiotic used to treat or prevent a variety of bacterial infections, including pneumonia, gynecological infections, bone and joint infections, and septicemia, among others.","['P0AD68', 'P02918', 'P02919', 'P0AD65', 'Q47066']","Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3).12Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, includingPseudomonas aeruginosa.4However, it is less active than first- and second-generation cephalosporins againstStaphylococcus aureusand other Gram-positive bacteria and also has low activity against anaerobes.4,9Ceftazidime has confirmed activity against clinically relevant Gram-negative bacteria includingCitrobacterspp.,Enterobacterspp.,Klebsiellaspp.,Proteusspp.,Serratia spp., _Escherichia coli,Haemophilus influenzae,Neisseria meningitidis,Pseudomonas aeruginosa, and some Gram-positive bacteria includingStaphylococcusspp. andStreptococcusspp. There are alsoin vitrodata for ceftazidime efficacy against a wide variety of other bacteria, such asAcinetobacter baumanniiandNeisseria gonorrhoeae, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria.12Although β-lactam antibiotics like ceftazidime are generally well tolerated, there remains a risk of serious acute hypersensitivity reactions, which is higher in patients with a known allergy to ceftazidime or any other β-lactam antibiotic. As with all antibiotics, ceftazidime may result in the overgrowth of non-susceptible organisms and potentially serious effects includingClostridium difficile-associated diarrhea (CDAD); CDAD should be considered in patients who develop diarrhea and, in confirmed cases, supportive care initiated immediately. Ceftazidime is primarily renally excreted such that high and prolonged serum concentrations can occur in patients with renal insufficiency, leading to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Treatment may lead to the development or induction of resistance with a risk of treatment failure. Periodic susceptibility testing should be considered, and monotherapy failure may necessitate the addition of another antibiotic such as an aminoglycoside. Cephalosporin use may decrease prothrombin activity, which may be improved by exogenous vitamin K. Inadvertent intra-arterial administration of ceftazidime may result in distal necrosis.12",[O-]C(=O)C1=C(CS[C@]2([H])[C@H](NC(=O)C(=N/OC(C)(C)C(O)=O)\C3=CSC(N)=N3)C(=O)N12)C[N+]1=CC=CC=C1,"The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan.Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as ""penicillin-binding proteins"" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal.,,Ceftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria.Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria.In vitroexperiments in Gram-negative bacteria such asEscherichia coli,Pseudomonas aeruginosa,Acinetobacter baumannii, andKlebsiella pneumoniaesuggest that ceftazidime primarily binds to PBP, with weaker binding to PBPa/b and PBP as well; although binding to other PBPs, such as PBP, is detectable, the concentrations required are much greater than those achieved clinically.,,,,Similarly, ceftazidime showed binding toStaphylococcus aureusPBP , , and with a much lower affinity for PBP.Recent data forMycobacterium abcessussuggest that ceftazidime can inhibit PonA, PonA, and PbpA at intermediate concentrations.TargetActionsOrganismAPeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorEscherichia coli (strain K)UBeta-lactamase Toho-substrateEscherichia coli",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta Lactam Antibiotics', 'beta-Lactams', 'Cephalosporins', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00554,Piroxicam,Piroxicamis an NSAID used to treat the symptoms of osteoarthritis and rheumatoid arthritis.,"['P35354', 'P23219']","Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis.",CN1C(C(=O)NC2=NC=CC=C2)=C(O)C2=C(C=CC=C2)S1(=O)=O,"The antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-. Piroxicam blocks the Cox- enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A, an aggregating agent, by the platelets.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Ophthalmologicals', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'Oxicams', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Sensory Organs', 'Sensory System Agents', 'Sulfur Compounds', 'Thiazines', 'Topical Products for Joint and Muscular Pain']" +DB00715,Paroxetine,"Paroxetineis a selective serotonin reuptake inhibitor used to treat major depressive disorder, panic disorder, OCD, social phobia, generalized anxiety disorder, the vasomotor symptoms of menopause, and premenstrual dysphoric disorder.","['P31645', 'P23975', 'P28223', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945', 'P14416', 'P35367', 'P08908', 'P28222', 'P28221', 'P28566', 'P30939', 'P28223', 'P41595', 'P28335', 'P46098', 'O95264', 'Q8WXA8', 'Q70Z44', 'A5X5Y0', 'Q13639', 'P50406', 'P34969', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P41595', 'P21728', 'P21918']","Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake.26,29,30The onset of action of paroxetine is reported to be approximately 6 weeks.18Due its serotonergic activity, paroxetine, like other SSRI drugs, may potentiate serotonin syndrome. This risk is especially high when monoamine oxidase (MAO) inhibitors are given within 2 weeks of paroxetine administration. Upon cessation of MAO inhibitors, a 2-week interval before paroxetine administration is recommended. Do not coadminister these agents.27",FC1=CC=C(C=C1)[C@@H]1CCNC[C@H]1COC1=CC2=C(OCO2)C=C1,"Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor.,This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, includingCitalopram,Fluoxetine, andFluvoxamine.The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information, but may occur due to its effects on thermoregulation.Paroxetine shows a clinically insignificant affinity for adrenergic alpha- and alpha- receptors and β-adrenergic receptors, dopamine D and D receptors, histamine H receptors and serotonin -HTA, -HTA and -HTC receptors.This drug shows some affinity for muscarinic cholinergic receptors and -HB receptors.,The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the -HT neurons. In rats, paroxetine activates -HTA receptors when it is first administered, inhibiting the stimulation of the -HT neurons and subsequent release of serotonin at the synaptic cleft.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansUSodium-dependent noradrenaline transporterinhibitorHumansU-hydroxytryptamine receptor AagonistHumansUAlpha- adrenergic receptorsbinderHumansUAlpha- adrenergic receptorsbinderHumansUBeta adrenergic receptorinhibitorHumansUDopamine D receptorother/unknownHumansUHistamine H receptorinhibitorHumansUSerotonin ReceptorsNot AvailableHumansUMuscarinic acetylcholine receptorinhibitorHumansU-hydroxytryptamine receptor BagonistHumansUD() dopamine receptorother/unknownHumans",[],"['Agents producing tachycardia', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Piperidines', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01156,Bupropion,"Bupropionis a norepinephrine and dopamine reuptake inhibitor used in the treatment of major depressive disorder (MDD), seasonal affective disorder (SAD), and as an aid to smoking cessation.","['Q01959', 'P23975', 'P32297', 'P46098']","Bupropion is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitors, or other known antidepressant agents. Compared to classical tricyclic antidepressants, Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine. In addition, Bupropion does not inhibit monoamine oxidase. Bupropion has been found to be essentially inactive at the serotonin transporter (SERT)(IC50 >10 000 nM),12however both bupropion and its primary metabolite hydroxybupropion have been found to block the function of cation-selective serotonin type 3A receptors (5-HT3ARs).Bupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behaviour tasks, and, at high doses, induction of mild stereotyped behaviourLabel. Due to these stimulant effects and selective activity at dopamine and norepinephrine receptors, bupropion has been identified as having an abuse potential.Label,17Bupropion has a similar structure to the controlled substanceCathinone, and has been identified as having mild amphetamine-like activity, particularly when inhaled or injected.17Bupropion is also known to lower the seizure threshold, making any pre-existing seizure conditions a contraindication to its use. This risk is exacerbated when bupropion is combined with other drugs or substances that lower the seizure threshold, such ascocaine, or in clinical situations that would increase the risk of a seizure such as abrupt alcohol or benzodiazepine withdrawal.LabelAs norepinephrine has been shown to have anticonvulsant properties, bupropion's inhibitory effects on NET are thought to contribute to its pro-convulsant activity.17Bupropion has been shown to increase blood pressure and pose a risk for exacerbation of unmanaged or pre-existing hypertension,18,Labelhowever, clinical trials of bupropion in smokers with CVD have not identified an increased incidence of CV events including stroke or heart attack.19In clinical trials, the mean increase in systolic blood pressure associated with the use of bupropion was found to be 1.3 mmHg.Label",CC(NC(C)(C)C)C(=O)C1=CC(Cl)=CC=C1,"Bupropion is a norepinephrine/dopamine-reuptake inhibitor (NDRI) that exerts its pharmacological effects by weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft, therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters. More specifically, bupropion binds to the norepinephrine transporter (NET) and the dopamine transporter (DAT).,Bupropion was originally classified as an ""atypical"" antidepressant because it does not exert the same effects as the classical antidepressants such as Monoamine Oxidase Inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), or Selective Serotonin Reuptake Inhibitors (SSRIs). While it has comparable effectiveness to typical first-line options for the treatment of depression such as SSRIs,,bupropion is a unique option for the treatment of MDD as it lacks any clinically relevant serotonergic effects, typical of other mood medications, or any effects on histamine or adrenaline receptors.,Lack of activity at these receptors results in a more tolerable side effect profile; bupropion is less likely to cause sexual side effects, sedation, or weight gain as compared to SSRIs or TCAs, for example.,When used as an aid to smoking cessation, bupropion is thought to confer its anti-craving and anti-withdrawal effects by inhibiting dopamine reuptake, which is thought to be involved in the reward pathways associated with nicotine, and through the antagonism of the nicotinic acetylcholinergic receptor (AChR), thereby blunting the effects of nicotine.,,Furthermore, the stimulatory effects produced by bupropion in the central nervous system are similar to nicotine's effects, making low doses of bupropion a suitable option as a nicotine substitute.When used in combination withnaltrexonein the marketed product ContraveⓇ for chronic weight management, the two components are thought to have effects on areas of the brain involved in the regulation of food intake. This includes the hypothalamus, which is involved in appetite regulation, and the mesolimbic dopamine circuit, which is involved in reward pathways.Studies have shown that the combined activity of bupropion andnaltrexoneincrease the firing rate of hypothalamic pro-opiomelanocortin (POMC) neurons and blockade of opioid receptor-mediated POMC auto-inhibition, which are associated with a reduction in food intake and increased energy expenditure.,,This combination was also found to reduce food intake when injected directly into the ventral tegmental area of the mesolimbic circuit in mice, which is an area associated with the regulation of reward pathways.TargetActionsOrganismASodium-dependent dopamine transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansU-hydroxytryptamine receptor Anegative modulatorHumans","['Smoking, Cessation', 'Weight Loss']","['Agents that reduce seizure threshold', 'Aminoketone Antidepressants', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antiobesity Preparations, Excl. Diet Products', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine And Norepinephrine Reuptake Inhibitors', 'Dopamine Uptake Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Increased Dopamine Activity', 'Increased Norepinephrine Activity', 'Ketones', 'Miscellaneous Antidepressants', 'Nervous System', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Uptake Inhibitors', 'OCT2 Inhibitors', 'Photosensitizing Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Smoking Cessation Agents']" +DB00316,Acetaminophen,"Acetaminophenis an analgesic drug used alone or in combination with opioids for pain management, and as an antipyretic agent.","['P35354', 'P23219', 'Q15185', 'Q8NER1']","Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to thesalicylatedrug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses.23Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation.Label,23Allergic reactions are rare occurrences following acetaminophen use.23",CC(=O)NC1=CC=C(O)C=C1,"According to its FDA labeling, acetaminophen's exact mechanism of action has not been fully establishedLabel- despite this, it is often categorized alongside NSAIDs (nonsteroidal anti-inflammatory drugs) due to its ability to inhibit the cyclooxygenase (COX) pathways.It is thought to exert central actions which ultimately lead to the alleviation of pain symptoms.One theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclooxygenase, COX- and COX-, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for eliciting pain sensations.Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX indirectly.Studies also suggest that acetaminophen selectively blocks a variant type of the COX enzyme that is unique from the known variants COX- and COX-.This enzyme has been referred to asCOX-. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat.The exact mechanism of action of this drug is not fully understood at this time, but future research may contribute to deeper knowledge.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansUProstaglandin E synthase inhibitorHumansUTransient receptor potential cation channel subfamily V member activatorHumans","['Airway secretion clearance therapy', 'Anti-spasmodics', 'Bronchodilation']","['Acetaminophen and Prodrugs', 'Amides', 'Amines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anilides', 'Aniline Compounds', 'Antipyretics', 'Central Nervous System Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Methemoglobinemia Associated Agents', 'Miscellaneous Analgesics and Antipyretics', 'Nervous System', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Sensory System Agents', 'UGT1A1 Substrates', 'UGT1A6 substrate', 'UGT1A9 Substrates']" +DB01413,Cefepime,"Cefepimeis a fourth-generation cephalosporin antibiotic used in the treatment of infections caused by susceptible bacteria, such as pneumonia, urinary tract infections, and skin infections.","['P02918', 'P02919', 'P0AD65', 'P0AD68', 'Q9X6W0', 'Q51504', 'Q9X6V3']","Cefepime is a fourth-generation cephalosporin antibiotic.5,6It is active against Gram-negative bacteria such asEnterobacterspp.,Escherichia coli,Klebsiella pneumoniae,Proteus mirabilisandPseudomonas aeruginosa, and Gram-positive bacteria such asStaphylococcus aureus(methicillin-susceptible isolates only),Streptococcus pneumoniae,Streptococcus pyogenesand Viridans group streptococci.5,6Compared to third-generation cephalosporins, cefepime has an extended Gram-negative coverage. Whereas other cephalosporins are degraded by plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and not significantly hydrolyzed by these enzymes.1,4Cefepime is also a poor inducer of type 1 beta-lactamases and, therefore, a good alternative against bacteria resistant to third-generation cephalosporins.1In animal models of infection, the time that the unbound plasma concentration of cefepime exceeds the minimum inhibitory concentration (MIC) of infecting organisms has been shown to correlate with treatment efficacy.5,6It has been suggested that cefepime can cross the inflamed blood-brain barrier.5,6This, along with its ability to inhibit γ-aminobutyric acid (GABA), could lead to the neurotoxic effects observed in some of the patients treated with cefepime.3,4",CO\N=C(/C(=O)N[C@@H]1C(=O)N2[C@]1([H])SCC(C[N+]1(C)CCCC1)=C2C([O-])=O)C1=CSC(N)=N1,"Cefepime is a bactericidal cephalosporin with a mode of action similar to other beta-lactam antibiotics.,Cefepime disrupts bacterial cell walls by binding and inhibiting transpeptidases known as penicillin-binding proteins (PBPs), which are enzymes involved in the final stages of peptidoglycan layer synthesis. This results in the lysis and death of susceptible microorganisms.Cefepime has a broad spectrum ofin vitroactivity that includes both Gram-positive and Gram-negative bacteria.,Cefepime has affinity for PBP- and PBP- inEscherichia coliandPseudomonas aeruginosa, as well as PBP- inE. coliandEnterobacter cloacae.TargetActionsOrganismAPenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorEscherichia coli (strain K)APeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorPseudomonas aeruginosaAPenicillin-binding protein inhibitorPseudomonas aeruginosaUPenicillin-binding protein inhibitorPseudomonas aeruginosa",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Fourth-Generation Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Neurotoxic agents', 'Sulfur Compounds', 'Thiazines']" +DB00688,Mycophenolate mofetil,"Mycophenolate mofetilis an inosine monophosphate dehydrogenase inhibitor used to prevent the rejection of kidney, heart, or liver transplants.","['P20839', 'P12268', 'Q03393']","Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA). The active form of mycophenolate, MPA, prevents the proliferation of immune cells and the formation of antibodies that cause transplant rejection.3The above effects lead to higher rates of successful transplantation, avoiding the devastating effects of graft rejection.",COC1=C(C\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C,"The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies. Lymphocyte and monocyte adhesion to endothelial cells of blood vessels that normally part of inflammation is prevented via the glycosylation of cell adhesion molecules by MPA.MPA inhibits de novo purine biosynthesis (that promotes immune cell proliferation) by inhibiting inosine ’-monophosphate dehydrogenase enzyme (IMPDH), with a preferential inhibition of IMPDH II.IMPDH normally transforms inosine monophosphate (IMP) to xanthine monophosphate (XMP), a metabolite contributing to the production of guanosine triphosphate (GTP).,,GTP is an important molecule for the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. As a result of the above cascade of effects, mycophenolate mofetil reduces de-novo production of guanosine nucleotides, interfering with the synthesis of DNA, RNA, and protein required for immune cell production.Further contributing to the above anti-inflammatory effects, MMF depletes tetrahydrobiopterin, causing the decreased function of inducible nitric oxide synthase enzyme, in turn decreasing the production of peroxynitrite, a molecule that promotes inflammation.TargetActionsOrganismAInosine-'-monophosphate dehydrogenase inhibitorinducerHumansAInosine-'-monophosphate dehydrogenase inhibitorHumansU-pyruvoyl tetrahydrobiopterin synthaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics, Antineoplastic', 'Antibiotics, Antitubercular', 'Antimetabolite Immunosuppressant', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fatty Acids', 'Immunologic Factors', 'Immunosuppressive Agents', 'IMP Dehydrogenase, antagonists & inhibitors', 'Lipids', 'Mycophenolic Acid and Prodrugs', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein substrates', 'UGT1A1 Substrates', 'UGT1A6 substrate', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB00502,Haloperidol,"Haloperidolis an antipsychotic agent used to treat schizophrenia and other psychoses, as well as symptoms of agitation, irritability, and delirium.","['P28335', 'P14416', 'P28223', 'P35462', 'Q99705', 'Q05940', 'Q99720', 'P35367', 'P20309', 'P35348', 'P08913', 'P18089', 'P18825', 'P08908', 'P50406', 'P34969', 'Q13224', 'P21728']","Use of the first-generation antipsychotics (including haloperidol) is considered highly effective for the management of the ""positive"" symptoms of schizophrenia including hallucinations, hearing voices, aggression/hostility, disorganized speech, and psychomotor agitation. However, this class is limited by the development of movement disorders such as drug-induced parkinsonism, akathisia, dystonia, and tardive dyskinesia, and other side effects including sedation, weight gain, and prolactin changes. Compared to the lower-potency first-generation antipsychotics such asChlorpromazine,Zuclopenthixol,Fluphenazine, andMethotrimeprazine, haloperidol typically demonstrates the least amount of side effects within class, but demonstrates a stronger disposition for causing extrapyramidal symptoms (EPS).6,7,8Low‐potency medications have a lower affinity for dopamine receptors so that a higher dose is required to effectively treat symptoms of schizophrenia. In addition, they block many receptors other than the primary target (dopamine receptors), such as cholinergic or histaminergic receptors, resulting in a higher incidence of side effects such as sedation, weight gain, and hypotension.The balance between the wanted drug effects on psychotic symptoms and unwanted side effects are largely at play within dopaminergic brain pathways affected by haloperidol. Cortical dopamine-D2-pathways play an important role in regulating these effects and include the nigrostriatal pathway, which is responsible for causing extrapyramidal symptoms (EPS), the mesolimbic and mesocortical pathways, which are responsible for the improvement in positive schizophrenic symptoms, and the tuberoinfundibular dopamine pathway, which is responsible for hyperprolactinemia.A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome.16Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving haloperidol. Higher than recommended doses of any formulation and intravenous administration of haloperidol appear to be associated with a higher risk of QT-prolongation and Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome).16A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.16",OC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1,"While haloperidol has demonstrated pharmacologic activity at a number of receptors in the brain, it exerts its antipsychotic effect through its strong antagonism of the dopamine receptor (mainly D), particularly within the mesolimbic and mesocortical systems of the brain. Schizophrenia is theorized to be caused by a hyperdopaminergic state within the limbic system of the brain.Dopamine-antagonizing medications such as haloperidol, therefore, are thought to improve psychotic symptoms by halting this over-production of dopamine. The optimal clinical efficacy of antipsychotics is associated with the blockade of approximately % - % of D receptors in the brain.While the exact mechanism is not entirely understood, haloperidol is known to inhibit the effects of dopamine and increase its turnover. Traditional antipsychotics, such as haloperidol, bind more tightly than dopamine itself to the dopamine D receptor, with dissociation constants that are lower than that for dopamine.It is believed that haloperidol competitively blocks post-synaptic dopamine (D) receptors in the brain, eliminating dopamine neurotransmission and leading to the relief of delusions and hallucinations that are commonly associated with psychosis. It acts primarily on the D-receptors and has some effect on -HT and α-receptors, with negligible effects on dopamine D-receptors. The drug also exerts some blockade of α-adrenergic receptors of the autonomic system.Antagonistic activity regulated through dopamine D receptors in the chemoreceptive trigger zone (CTZ) of the brain renders its antiemetic activity. Of the three D-like receptors, only the D receptor is blocked by antipsychotic drugs in direct relation to their clinical antipsychotic abilities.Clinical brain-imaging findings show that haloperidol remains tightly bound to D dopamine receptors in humans undergoing positron emission tomography (PET) scans with a h pause in between scans.A common adverse effect of this drug is the development of extrapyramidal symptoms (EPS), due to this tight binding of haloperidol to the dopamine D receptor.Due to the risk of unpleasant and sometimes lifelong extrapyramidal symptoms, newer antipsychotic medications than haloperidol have been discovered and formulated. Rapid dissociation of drugs from dopamine D receptors is a plausible explanation for the improved EPS profile of atypical antipsychotics such asRisperidone. This is also consistent with the theory of a lower affinity for D receptors for these drugs. As mentioned above, haloperidol binds tightly to the dopamine receptor, potentiating the risk of extrapyramidal symptoms,and therefore should only been used when necessary.TargetActionsOrganismA-hydroxytryptamine receptor CNot AvailableHumansADopamine D receptorantagonistHumansU-hydroxytryptamine receptor Aother/unknownHumansUDopamine D receptorinverse agonistHumansUMelanin-concentrating hormone receptor Not AvailableHumansUSynaptic vesicular amine transporterNot AvailableHumansUSigma non-opioid intracellular receptor Not AvailableHumansUHistamine H receptorNot AvailableHumansUMuscarinic acetylcholine receptor MNot AvailableHumansUAlpha-A adrenergic receptorNot AvailableHumansUAlpha-A adrenergic receptorNot AvailableHumansUAlpha-B adrenergic receptorNot AvailableHumansUAlpha-C adrenergic receptorNot AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumansU-hydroxytryptamine receptor Not AvailableHumansU-hydroxytryptamine receptor Not AvailableHumansUGlutamate receptor ionotropic, NMDA BantagonistHumansUDopamine D receptorantagonistHumans",[],"['Agents that reduce seizure threshold', 'Anti-Dyskinesia Agents', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Autonomic Agents', 'Butyrophenone Derivatives', 'Butyrophenones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Hyperglycemia-Associated Agents', 'Ketones', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Tranquilizing Agents', 'UGT1A9 Substrates']" +DB01388,Mibefradil,Mibefradil was withdrawn from the market in 1998 because of potentially harmful interactions with other drugs.,"['O43497', 'O95180', 'Q13936', 'Q01668', 'O60840', 'Q9P0X4', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305']","Mibefradil belongs to a group of medicines called calcium channel blocking agents, or, more commonly, calcium channel blockers. Calcium channel blocking agents affect the movement of calcium into the cells of the heart and blood vessels. As a result, they relax blood vessels and increase the supply of blood and oxygen to the heart while reducing its workload. Mibefradil is a benzimidazoyl-substituted tetraline that selectively binds and inhibits T-type calcium channels.",COCC(=O)O[C@]1(CCN(C)CCCC2=NC3=CC=CC=C3N2)CCC2=C(C=CC(F)=C2)[C@@H]1C(C)C,"Mibefradil is a tetralol calcium channel blocking agent that inhibits the influx of calcium ions across both the T (low-voltage) and L (high-voltage) calcium channels of cardiac and vascular smooth muscle, with a greater selectivity for T channels. Vasodilation occurs in vascular smooth muscle, causing a decrease in peripheral vascular resistance and a resulting decrease in blood pressure. Mibefradil causes a slight increase in cardiac output during chronic dosing. Mibefradil slows sinus and atrioventricular (AV) node conduction, producing a slight reduction in heart rate and a slight increase in the PR interval. It has also been shown to slightly lengthen the corrected sinus node recovery time and AH interval and to raise the Wenckebach point. The mechanism by which mibefradil reduces angina is not known, but is thought to be attributed to a reduction in heart rate, total peripheral resistance (afterload), and the heart rate–systolic blood pressure product at any given level of exercise. The result of these effects is a decrease in cardiac workload and myocardial oxygen demand.TargetActionsOrganismAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-FinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Benzimidazoles', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Naphthalenes', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Tetrahydronaphthalenes', 'Vasodilating Agents']" +DB00184,Nicotine,Nicotineis a stimulatory alkaloid found in tobacco products that is often used for the relief of nicotine withdrawal symptoms and as an aid to smoking cessation.,"['P43681', 'P36544', 'P17787', 'Q15822', 'P32297', 'P30532', 'Q15825', 'Q9UGM1', 'Q9GZZ6', 'Q05901', 'P30926', 'P11511', 'P28329']","Nicotine, the primary alkaloid in tobacco products binds stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at the locus ceruleus and a reward effect in the limbic system. Itranvenous administration of nicotine causes release of acetylcholine, norepinephrine, dopamine, serotonine, vasopressin, beta-endorphin and ACTH. Nicotine is a highly addictive substance. Nicotine also induces peripheral vasoconstriction, tachycardia and elevated blood pressure. Nicotine inhalers and patches are used to treat smoking withdrawl syndrome. Nicotine is classified as a stimulant of autonomic ganglia.",CN1CCC[C@H]1C1=CN=CC=C1,"Nicotine is a stimulant drug that acts as an agonist at nicotinic acetylcholine receptors. These are ionotropic receptors composed up of five homomeric or heteromeric subunits. In the brain, nicotine binds to nicotinic acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways. This causes the channel to open and allow conductance of multiple cations including sodium, calcium, and potassium. This leads to depolarization, which activates voltage-gated calcium channels and allows more calcium to enter the axon terminal. Calcium stimulates vesicle trafficking towards the plasma membrane and the release of dopamine into the synapse. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine. +Nicotine also binds to nicotinic acetylcholine receptors on the chromaffin cells in the adrenal medulla. Binding opens the ion channel allowing influx of sodium, causing depolarization of the cell, which activates voltage-gated calcium channels. Calcium triggers the release of epinephrine from intracellular vesicles into the bloodstream, which causes vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-agonistHumansANeuronal acetylcholine receptor subunit alpha-agonistHumansANeuronal acetylcholine receptor subunit beta-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit beta-agonistHumansUNeuronal acetylcholine receptor subunit beta-agonistHumansUCytochrome P AinhibitorHumansUCholine O-acetyltransferaseinhibitorHumans",['Smoking cessation therapy'],"['Agents producing tachycardia', 'Alkaloids', 'Autonomic Agents', 'Cholinergic Agents', 'Cholinergic Agonists', 'Cholinergic Nicotinic Agonist', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Addictive Disorders', 'Drugs Used in Nicotine Dependence', 'Ganglion Blockers', 'Ganglionic Stimulants', 'Miscellaneous Autonomic Drugs', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nervous System', 'Neurotransmitter Agents', 'Nicotine, antagonists & inhibitors', 'Nicotinic Agonists', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Peripheral Nervous System Agents', 'Pyridines', 'Smoking Cessation Agents', 'Solanaceous Alkaloids']" +DB00493,Cefotaxime,Cefotaximeis a third generation cephalosporin used to treat susceptible Gram negative and Gram positive bacterial infections.,"['Q7CRA4', 'Q8DNB6', 'P42971', 'Q8DR59', 'P0A3M6', 'Q4U2R8', 'Q8TCC7', 'Q9NSA0', 'Q9Y694', 'P46059', 'P02768', 'B2ZTR6', 'Q16348']",Cefotaxime is a third generation intravenous cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity againstPseudomonas aeruginosa. Cefotaxime works by inhibiting bacterial cell wall biosynthesis. A positive feature of cefotaxime is that it display a resistance to penicillinases and is useful to treat infections that are resistant to penicillin derivatives.,[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O,The bactericidal activity of cefotaxime results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefotaxime shows high affinity for penicillin-binding proteins in the cell wall including PBP Ib and PBP III.TargetActionsOrganismAPenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorBacillus subtilis (strain )APenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)USolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSerum albuminNot AvailableHumansUBeta-lactamaseNot AvailableAcinetobacter baumanniiUSolute carrier family member Not AvailableHumans,[],"['Agents that reduce seizure threshold', 'Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB09061,Cannabidiol,"Cannabidiolis an active cannabinoid used as an adjunctive treatment for the management of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome and symptomatic relief of moderate to severe neuropathic pain or other painful conditions, like cancer.","['P21554', 'P34972', 'P47775', 'P23415', 'P23415', 'P48167', 'O75311', 'Q14330', 'Q9Y2T6', 'P08908', 'P28223', 'P36544', 'P41143', 'P35372', 'P37231', 'Q8NER1', 'O43497', 'O95180', 'Q9P0X4', 'O75762', 'Q7Z2W7', 'Q9Y5S1', 'Q8NET8', 'Q9HBA0', 'P21796', 'P46098', 'P30542', 'P23219', 'P35354', 'P24752', 'P05093', 'P04035', 'P00390', 'P07203', 'P14902', 'Q16678', 'P15559', 'P04040', 'P20815', 'P10635', 'P00441', 'P05177', 'P24462', 'F1T0I5', 'Q02083']","Although the exact mechanism and magnitude of effects of THC and CBD are not fully understood, CBD has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity. This wide variety of effects is likely due to it's complex pharmacological mechanisms. In addition to binding to CB1 and CB2 receptors of the endocannabinoid system, there is evidence that CBD activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH)1,2.",CCCCCC1=CC(O)=C([C@@H]2C=C(C)CC[C@H]2C(C)=C)C(O)=C1,"The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems, including the brain. The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood. More specifically, CB receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes.CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body. Allosteric regulation of a receptor is achieved through the modulation of the activity of a receptor on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects.TargetActionsOrganismACannabinoid receptor antagonistmodulatorHumansUCannabinoid receptor antagonistHumansUG-protein coupled receptor inverse agonistHumansUGlycine receptor subunit alpha-Not AvailableHumansUGlycine receptor (alpha-/beta)allosteric modulatorHumansUGlycine receptor subunit alpha-potentiatorHumansUN-arachidonyl glycine receptorNot AvailableHumansUG-protein coupled receptor antagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor AagonistHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUDelta-type opioid receptorNot AvailableHumansUMu-type opioid receptorNot AvailableHumansUPeroxisome proliferator-activated receptor gammaactivatorHumansUTransient receptor potential cation channel subfamily V member activatorHumansUVoltage-dependent T-type calcium channel subunit alpha-GNot AvailableHumansUVoltage-dependent T-type calcium channel subunit alpha-HNot AvailableHumansUVoltage-dependent T-type calcium channel subunit alpha-INot AvailableHumansUTransient receptor potential cation channel subfamily A member agonistHumansUTransient receptor potential cation channel subfamily M member Not AvailableHumansUTransient receptor potential cation channel subfamily V member activatorHumansUTransient receptor potential cation channel subfamily V member activatorHumansUTransient receptor potential cation channel subfamily V member activatorHumansUVoltage-dependent anion-selective channel protein Not AvailableHumansU-hydroxytryptamine receptor AantagonistHumansUAdenosine receptor AactivatorHumansUProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumansUAcetyl-CoA acetyltransferase, mitochondrialinhibitorHumansUSteroid -alpha-hydroxylase/, lyaseinhibitorHumansU-hydroxy--methylglutaryl-coenzyme A reductasestimulatorHumansUGlutathione reductase, mitochondrialstimulatorHumansUGlutathione peroxidase stimulatorHumansUIndoleamine ,-dioxygenase inhibitorHumansUCytochrome P BinhibitorHumansUNAD(P)H dehydrogenase [quinone] inhibitorHumansUCatalaseinhibitorHumansUCytochrome P AinhibitorHumansUCytochrome P DinhibitorHumansUSuperoxide dismutase [Cu-Zn]inhibitorHumansUCytochrome P AinhibitorHumansUCytochrome P AinhibitorHumansUArylalkylamine N-acetyltransferaseinhibitorHumansUN-acylethanolamine-hydrolyzing acid amidaseinhibitorHumans",[],"['Agents producing tachycardia', 'Agents that produce hypertension', 'Anticonvulsants', 'Antidepressive Agents', 'BCRP/ABCG2 Inhibitors', 'Cannabinoids and similars', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (weak)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Nervous System', 'P-glycoprotein inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Terpenes', 'UGT1A9 Inhibitors', 'UGT1A9 Substrates', 'UGT2B17 substrates', 'UGT2B7 Inhibitors', 'UGT2B7 substrates']" +DB00904,Ondansetron,Ondansetronis a serotonin 5-HT3 receptor antagonist used to prevent nausea and vomiting in cancer chemotherapy and postoperatively.,"['P46098', 'Q13639', 'P35372', 'P08908', 'P28222']","Ondansetron is a highly specific and selective serotonin 5-HT3receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptorsLabel,3,4. The serotonin 5-HT3receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postremaLabel,3,4. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents, suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tractLabel,3,4. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomitingLabel,3,4.Moreover, the effect of ondansetron on the QTc interval was evaluated in a double-blind, randomized, placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and women11,12. Ondansetron was tested at single doses of 8 mg and 32 mg infused intravenously over 15 minutes11,12. At the highest tested dose of 32 mg, prolongation of the Fridericia-corrected QTc interval (QT/RR0.33=QTcF) was observed from 15 min to 4 h after the start of the 15 min infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 19.6 (21.5) msec at 20 min11,12. At the lower tested dose of 8 mg, QTc prolongation was observed from 15 min to 1 h after the start of the 15-minute infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 5.8 (7.8) msec at 15 min11,12. The magnitude of QTc prolongation with ondansetron is expected to be greater if the infusion rate is faster than 15 minutes11,12. The 32 mg intravenous dose of ondansetron must not be administered11,12. No treatment-related effects on the QRS duration or the PR interval were observed at either the 8 or 32 mg dose11,12.An ECG assessment study has not been performed for orally administered ondansetron11,12. On the basis of pharmacokinetic-pharmacodynamic modelling, an 8 mg oral dose of ondansetron is predicted to cause a mean QTcF increase of 0.7 ms (90% CI -2.1, 3.3) at steady-state, assuming a mean maximal plasma concentration of 24.7 ng/mL (95% CI 21.1, 29.0)11,12. The magnitude of QTc prolongation at the recommended 5 mg/m2 dose in pediatrics has not been studied, but pharmacokinetic-pharmacodynamic modeling predicts a mean increase of 6.6 ms (90% CI 2.8, 10.7) at maximal plasma concentrations11,12.In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time10. Multiday administration of ondansetron has been shown to slow colonic transit in healthy subjects10. Ondansetron has no effect on plasma prolactin concentrations10.",CN1C2=C(C3=CC=CC=C13)C(=O)C(CN1C=CN=C1C)CC2,"Ondansetron is a selective antagonist of the serotonin receptor subtype, -HT,,.Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of -HT receptors located on vagal afferents,,. Ondansetron may block the initiation of this reflex. Activation of vagal afferents may also cause a central release of serotonin from the chemoreceptor trigger zone of the area postrema, located on the floor of the fourth ventricle,,. Thus, the antiemetic effect of ondansetron is probably due to the selective antagonism of -HT receptors on neurons located in either the peripheral or central nervous systems, or both,,.Although the mechanisms of action of ondansetron in treating postoperative nausea and vomiting and cytotoxic induced nausea and vomiting may share similar pathways, the role of ondansetron in opiate-induced emesis has not yet been formally established,.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor agonistHumansUMu-type opioid receptorother/unknownHumansU-hydroxytryptamine receptor Aother/unknownHumansU-hydroxytryptamine receptor Bother/unknownHumans",[],"['Anti-Anxiety Agents', 'Antidepressive Agents', 'Antiemetic Serotonin 5-HT3 Receptor Antagonists', 'Antiemetics', 'Antiemetics and Antinauseants', 'Carbazoles', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Imidazoles', 'Indoles', 'Moderate Risk QTc-Prolonging Agents', 'Peripheral Nervous System Agents', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 3 Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB08846,Ellagic acid,"Ellagic acid is present in several fruits such as cranberries, strawberries, raspberries, and pomegranates. In pomegranates, there are several therapeutic compounds but ellagic acid is the most active and abundant. Ellagic acid is also present in vegetables. Ellagic acid is an investigational drug studied for treatment of Follicular Lymphoma (phase 2 trial), protection from brain injury of intrauterine growth restricted babies (phase 1 and 2 trial), improvement of cardiovascular function in adolescents who are obese (phase 2 trial), and topical treatment of solar lentigines. Ellagic acid's therapeutic action mostly involves antioxidant and anti-proliferative effects.","['P00915', 'P00918', 'P07451', 'P22748', 'P35218', 'Q9Y2D0', 'P23280', 'P43166', 'Q16790', 'O43570', 'Q9ULX7', 'P68400', 'P17612', 'P17252', 'P05771', 'P43405', 'Q14534']",Ellagic acid's therapeutic action mostly involves antioxidant and anti-proliferative/anti-cancer effects.,OC1=C(O)C2=C3C(=C1)C(=O)OC1=C3C(=CC(O)=C1O)C(=O)O2,"The exact mechanism of action of ellagic acid in its different potential indications is still being investigated.TargetActionsOrganismUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase A, mitochondrialinhibitorHumansUCarbonic anhydrase B, mitochondrialinhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCasein kinase II subunit alphainhibitorHumansUcAMP-dependent protein kinase catalytic subunit alphainhibitorHumansUProtein kinase C alpha typeinhibitorHumansUProtein kinase C beta typeinhibitorHumansUTyrosine-protein kinase SYKinhibitorHumansUSqualene monooxygenaseinhibitorHumans",[],"['Benzopyrans', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Substrates', 'Pyrans']" +DB00279,Liothyronine,"Liothyronineis a thyroid hormone replacement therapy used to treat hypothyroidism, to suppress TSH, and to help in the diagnosis of hyperthyroidism.","['P10827', 'P10828', 'P12004']","In hormonal replacement, liothyronine is more potent and present a faster action when compared to levothyroxine but the time of action is significantly shorter. The type of treatment needs to be well evaluated as the fast correction of thyroid hormones in certain diseases presents additional risks such as heart failure.3The onset of activity is observed a few hours after administration and the maximum effect is observed after 2-3 days.LabelTreatment with liothyronine has been shown to produce normal plasma levels of T3 hormone but to have no effect on the T4 plasma concentration.5",N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1)C(O)=O,"Liothyronine replaces endogenous thyroid hormone and then exerts its physiologic effects by controlling DNA transcription and protein synthesis. This effect on DNA is obtained by the binding of liothyronine to the thyroid receptors attached to DNA. Exogenous liothyronine exerts all the normal effects of the endogenous thyroid T hormone. Hence, it increases energy expenditure, accelerates the rate of cellular oxidation stimulating growth, maturation, and metabolism of the body tissues, aids in myelination of nerves and development of synaptic processes in the nervous system and enhances carbohydrate and protein metabolism.TargetActionsOrganismAThyroid hormone receptor alphaagonistHumansAThyroid hormone receptor betaagonistHumansUProliferating cell nuclear antigenantagonistHumans",['Supplemental or replacement therapy'],"['Agents used to treat hypothyroidism', 'Drugs that are Mainly Renally Excreted', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'l-Triiodothyronine', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein inducers', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroid Products', 'Thyronines', 'Thyroxine-binding globulin substrates', 'Triiodothyronine', 'UGT1A1 Substrates']" +DB00926,Etretinate,"Etretinate is a medication used to treat severe psoriasis. It is a synthetic aromatic retinoid. The mechanism of action of etretinate is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. It is thought to bind to the retinoic acid receptors. Etretinate is also believed to enhance the binding of cAMP to the regulatory RI subunit of cAMP dependent protein kinases. Etretinate was taken off the market in Canada in 1996 and America in 1998 due to the risk of birth defects. Etretinate is now used to treat T-cell lymphomas. It also appears to inhibit NADH oxidase activity.","['P10276', 'P19793', 'P10826', 'P48443', 'P28702', 'P13631']","The active metabolite responsible for etretinate's effects, acitretin, is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.",CCOC(=O)C=C(C)C=CC=C(C)C=CC1=C(C)C(C)=C(OC)C=C1C,"The mechanism of action of the active metabolite, acitretin, is unknown, however it is believed to work by targeting specific receptors (retinoid receptors) in the skin which help normalize the growth cycle of skin cells.TargetActionsOrganismARetinoic acid receptor alphaagonistHumansARetinoic acid receptor RXR-alphaagonistHumansARetinoic acid receptor betaagonistHumansARetinoic acid receptor RXR-gammaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor gammaagonistHumans",[],"['Alkenes', 'Antipsoriatics', 'Antipsoriatics for Systemic Use', 'Biological Factors', 'Carotenoids', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Hydrocarbons, Acyclic', 'Keratolytic Agents', 'Photosensitizing Agents', 'Pigments, Biological', 'Polyenes', 'Retinoids', 'Retinoids for Treatment of Psoriasis', 'Terpenes']" +DB01005,Hydroxyurea,"Hydroxyureais an antimetabolite used to treat sickle cell anemia crisis, resistant chronic myeloid leukemia, and Locally advanced squamous cell carcinomas of the head and neck (excluding the lip).",['P23921'],"The correlation between hydroxyurea concentrations, reduction of crisis rate, and increase in HbF, is not known.16",NC(=O)NO,"The precise mechanism by which hydroxyurea produces its antineoplastic effects cannot, at present, be described. However, the reports of various studies in rat and human tissue cultures lend support to the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis, by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. Hydroxyurea probably acts by decreasing the rate of conversion of ribonucleotides and deoxyribonucleotides. This effect is particularly apparent in cells with a high rate of proliferation.Particularly, hydroxyurea reduces the tyrosyl free radical at the active site of the M via a one-electron transfer reaction through the –NH-OH moiety.Three mechanisms have been postulated for the potentiation of the therapeutic effects of irradiation by hydroxyurea on squamous cell (epidermoid) carcinomas of the head and neck. In vitro studies utilizing Chinese hamster cells suggest that hydroxyurea is lethal to normally radioresistant S-stage cells and holds other cells of the cell cycle in the G or pre-DNA synthesis stage where they are most susceptible to the effects of irradiation. The third mechanism of action has been theorized on the basis of in vitro studies of HeLa cells: it appears that hydroxyurea, by inhibition of DNA synthesis, hinders the normal repair process of cells damaged but not killed by irradiation, thereby decreasing their survival rate; there is no alteration of RNA and protein syntheses.Another proposed mechanism of action of hydroxyurea is the elevation of HbF concentrations in Sickle Cell Disease patients. HbF interferes with the polymerization of HbS (sickle haemoglobin) and thus impedes the sickling of red blood cell. Recently, hydroxyurea has shown to be associated with the generation of nitric oxide, suggesting that nitric oxide stimulates cyclic guanosine monophosphates (cGMP) production, which then activates a protein kinase and increases the production of HbF. Other known pharmacological effects of hydroxycarbamide which may contribute to its beneficial effects in Sickle Cell Disease include decrease of neutrophils, improved deformability of sickled cells, and altered adhesion of red blood cells to the endothelium.TargetActionsOrganismARibonucleoside-diphosphate reductase large subunitinhibitorHumans","['Chemoradiotherapy', 'Radiation Therapy']","['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Antisickling Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Hematologic Agents', 'Immunosuppressive Agents', 'Methemoglobinemia Associated Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nucleic Acid Synthesis Inhibitors', 'OATP1B1/SLCO1B1 Substrates']" +DB00470,Dronabinol,Dronabinolis a synthetic delta-9-THC used in the treatment of anorexia and weight loss in HIV patients as well as nausea and vomiting in cancer chemotherapy.,"['P21554', 'P34972']","Dronabinol-induced sympathomimetic activity may result in tachycardia and/or conjunctival injection. Its effects on blood pressure are inconsistent, but subjects have experienced orthostatic hypotension and/or syncope upon abrupt standing.8Dronabinol also demonstrates reversible effects on appetite, mood, cognition, memory, and perception. These phenomena appear to be dose-related, increasing in frequency with higher dosages, and subject to great inter-patient variability. After oral administration, dronabinol capsules have an onset of action of approximately 0.5 to 1 hour and a peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect of dronabinol may continue for 24 hours or longer after administration.8Tachyphylaxis and tolerance develop to some of the cardiovascular and CNS pharmacologic effects of dronabinol with chronic use, suggesting an indirect effect on sympathetic neurons. In a study of the pharmacodynamics of chronic dronabinol exposure, healthy male subjects (N = 12) received 12 times the maximum dose for anorexia associated with weight loss in patients with AIDS of dronabinol capsules in divided doses for 16 days. An initial tachycardia induced by dronabinol was replaced successively by normal sinus rhythm and then bradycardia. A decrease in supine blood pressure, made worse by standing, was also observed initially. These +subjects developed tolerance to the cardiovascular and subjective adverse CNS effects of dronabinol within 12 days of treatment initiation.8Tachyphylaxis and tolerance do not appear to develop to the appetite stimulant effect of dronabinol. In clinical studies of dronabinol capsules in AIDS patients, at the recommended dosage, the appetite stimulant effect was sustained for up to five months.8",[H][C@@]12C=C(C)CC[C@@]1([H])C(C)(C)OC1=C2C(O)=CC(CCCCC)=C1,"Dronabinol is a synthetic form of delta--tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis (marijuana). THC demonstrates its effects through weak partial agonist activity at Cannabinoid- (CBR) and Cannabinoid- (CBR) receptors, which results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes.TargetActionsOrganismACannabinoid receptor agonistHumansACannabinoid receptor agonistHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Analgesics', 'Analgesics, Non-Narcotic', 'Antiemetics and Antinauseants', 'BCRP/ABCG2 Inhibitors', 'Cannabinoid Receptor Agonists', 'Cannabinoids and similars', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hallucinogens', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Miscellaneous Antiemetics', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Psychotropic Drugs', 'Sensory System Agents', 'Terpenes', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A9 Substrates']" +DB01050,Ibuprofen,"Ibuprofenis an NSAID and non-selective COX inhibitor used to treat mild-moderate pain, fever, and inflammation.","['P35354', 'P23219', 'P10415', 'P07204', 'P12104', 'P37231', 'P13569', 'Q07869', 'P07359', 'P31151']","Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials.23The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region.23The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen.23The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms.10Ibuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility.17As well, it has been reported to reduce significantly the fever and the pain caused by migraines.18,19This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system.23In the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time.20On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition.21The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer.22",CC(C)CC1=CC=C(C=C1)C(C)C(O)=O,"The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway.Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX- and COX-. The inhibition of COX- activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX- is thought to cause some of the side effects of ibuprofen including GI ulceration.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansUApoptosis regulator Bcl-modulatorHumansUThrombomodulininducerHumansUFatty acid-binding protein, intestinalbinderHumansUPeroxisome proliferator-activated receptor gammaactivatorHumansUCystic fibrosis transmembrane conductance regulatorinhibitorHumansUPeroxisome proliferator-activated receptor alphaactivatorHumansUPlatelet glycoprotein Ib alpha chaininducerHumansUProtein S-AinducerHumans",[],"['Acids, Carbocyclic', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antiinflammatory Products for Vaginal Administration', 'Antirheumatic Agents', 'Central Nervous System Agents', 'COX-1 Inhibitors', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Experimental Unapproved Treatments for COVID-19', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP2B1/SLCO2B1 substrates', 'Other Nonsteroidal Anti-inflammatory Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Pharmaceutical Preparations', 'Phenylpropionates', 'Propionates', 'Sensory System Agents', 'Throat Preparations', 'Topical Products for Joint and Muscular Pain', 'UDP Glucuronosyltransferases Inhibitors', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B17 Inhibitors', 'UGT2B7 substrates']" +DB01242,Clomipramine,"Clomipramineis a tricyclic antidepressant used in the treatment of obsessive-compulsive disorder and disorders with an obsessive-compulsive component, such as depression, schizophrenia, and Tourette’s disorder.","['P31645', 'P28223', 'P41595', 'P28335', 'P23975', 'P09211']","Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α1and β1receptors are sensitized, α2receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.",CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2,"Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor BantagonistHumansA-hydroxytryptamine receptor CantagonistHumansUSodium-dependent noradrenaline transporterinhibitorHumansUGlutathione S-transferase PinhibitorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dibenzazepines', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein inhibitors', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tertiary amine tricyclic antidepressants', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB00255,Diethylstilbestrol,"A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)","['Q92731', 'P03372', 'P62508', 'P11474', 'O95718', 'Q15596', 'O75469', 'P10275', 'P04278']","Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring.",CC\C(=C(\CC)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1,"Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).TargetActionsOrganismAEstrogen receptor betaagonistHumansAEstrogen receptor alphaagonistHumansAEstrogen-related receptor gammaagonistHumansUSteroid hormone receptor ERRNot AvailableHumansUSteroid hormone receptor ERRNot AvailableHumansUNuclear receptor coactivator Not AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumansUAndrogen receptorantagonistHumansUSex hormone-binding globulinNot AvailableHumans",[],"['Adrenal Cortex Hormones', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Benzene Derivatives', 'Benzylidene Compounds', 'BSEP/ABCB11 Substrates', 'Carcinogens', 'COMT Substrates', 'Contraceptive Agents, Female', 'Contraceptive Agents, Male', 'Contraceptives, Postcoital', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Estrogen Contraceptives', 'Estrogens', 'Estrogens, Non-Steroidal', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Noxae', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP2B1/SLCO2B1 substrates', 'P-glycoprotein substrates', 'Sex Hormones and Modulators of the Genital System', 'Stilbenes', 'Stilbestrols', 'Synthetic Estrogens, Plain', 'Thyroxine-binding globulin inducers', 'Toxic Actions']" +DB00698,Nitrofurantoin,Nitrofurantoinis an antibiotic used to treat urinary tract infections.,"['P52647', 'P17117', 'P0A7R5']","Nitrofurantoin interferes with vital processes in bacteria, which leads to their death.2Nitrofurantoin rapidly reaches therapeutic concentrations in the urine and is also cleared rapidly.3",[O-][N+](=O)C1=CC=C(O1)\C=N\N1CC(=O)NC1=O,"Nitrofurantoin is converted by bacterial nitroreductases to electrophilic intermediates which inhibit the citric acid cycle as well as synthesis of DNA, RNA, and protein.TargetActionsOrganismAProbable pyruvate-flavodoxin oxidoreductasepotentiatorEscherichia coli (strain K)AOxygen-insensitive NADPH nitroreductasepotentiatorEscherichia coli (strain K)US ribosomal protein SinhibitorEscherichia coli (strain K)",[],"['Agents causing hyperkalemia', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'Drugs that are Mainly Renally Excreted', 'Furans', 'Methemoglobinemia Associated Agents', 'Nitro Compounds', 'Nitrofuran Antibacterial', 'Nitrofuran Derivatives', 'Nitrofurans', 'P-glycoprotein substrates', 'Renal Agents', 'Thyroxine-binding globulin substrates']" +DB00475,Chlordiazepoxide,"Chlordiazepoxideis a benzodiazepine used to treat the withdrawal symptoms of acute alcoholism, to treat preoperative anxiety, and to treat anxiety over a short term period.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Chlordiazepoxide has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The drug seems to block EEG arousal from stimulation in the brain stem reticular formation. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses. Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide revealed a ""taming"" action with the elimination of fear and aggression. The taming effect of chlordiazepoxide was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.",CNC1=NC2=C(C=C(Cl)C=C2)C(C2=CC=CC=C2)=[N+]([O-])C1,"Chlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA (A) receptor complexes at several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA(A) receptor. BZDs, therefore, enhance GABA-mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization. The net neuro-inhibitory effects result in the observed sedative, hypnotic, anxiolytic, and muscle relaxant properties.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Adjuvants, Anesthesia', 'Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Cytosine Nucleotides', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleotides', 'Psycholeptics', 'Psychotropic Drugs', 'Pyrimidine Nucleotides', 'Pyrimidines', 'Ribonucleotides', 'Tranquilizing Agents']" +DB00468,Quinine,Quinineis an alkaloid used to treat uncomplicated Plasmodium falciparum malaria.,"['P14770', 'O15554']","Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.",[H][C@]1(C[C@@H]2CC[N@]1C[C@@H]2C=C)[C@H](O)C1=CC=NC2=CC=C(OC)C=C12,"The theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.TargetActionsOrganismAFe(II)-protoporphyrin IXantagonistPlasmodium falciparumUPlatelet glycoprotein IXotherHumansUIntermediate conductance calcium-activated potassium channel protein inhibitorHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Agents that reduce seizure threshold', 'Alkaloids', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Infective Agents', 'Antimalarial methanolquinolines', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Blood Glucose Lowering Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cinchona Alkaloids', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Herbs (Hypotensive Properties)', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Hypoglycemia-Associated Agents', 'Methemoglobinemia Associated Agents', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinuclidines', 'Sensory System Agents']" +DB00916,Metronidazole,"Metronidazoleis a nitroimidazole used to treat trichomoniasis, amebiasis, inflammatory lesions of rosacea, and bacterial infections, as well as prevent postoperative infections.",['O25608'],"Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities.16Metronidazole is an effective treatment for some anaerobic bacterial infections.11Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action against facultative anaerobes or obligate aerobes.14The nitro group reduction of metronidazole by anaerobic organisms is likely responsible for the drug's antimicrobial cytotoxic effects, causing DNA strand damage to microbes.5,7A note on convulsions and neuropathy and carcinogenesisIt is important to be aware of the risk of peripheral neuropathy and convulsions associated with metronidazole, especially at higher doses. If convulsions or numbness of an extremity occur, discontinue the drug immediately.14Metronidazole has been found to be carcinogenic in mice and rats. The relevance to this effect in humans is unknown. It is advisable to only administer metronidazole when clinically necessary and only for its approved indications.17",CC1=NC=C(N1CCO)[N+]([O-])=O,"The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis.After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. +The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms.TargetActionsOrganismAOxygen-insensitive NADPH nitroreductasepotentiatorHelicobacter pylori (strain ATCC / )UAnaerobic bacterial DNAinhibitorUProtozoal DNAinhibitor",[],"['Agents that reduce seizure threshold', 'Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Antiinfectives for Systemic Use', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Imidazole Derivatives', 'Imidazoles', 'Miscellaneous Antiprotozoals', 'Miscellaneous Local Anti-infectives', 'Nitro Compounds', 'Nitroimidazole Antimicrobial', 'Nitroimidazole Derivatives', 'Nitroimidazoles', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Stomatological Preparations', 'UGT1A1 Substrates']" +DB00433,Prochlorperazine,Prochlorperazineis a phenothiazine derivative used in the treatment of schizophrenia and anxiety and to relieve severe nausea and vomiting.,"['P14416', 'P35367', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Prochlorperazine is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons.10It also exerts its anti-emetic actions via anti-dopaminergic effects, where it displays similar efficacy as ondansteron, a 5HT-3 receptor antagonist and anti-emetic, in preventing delayed nausea and vomiting.3Prochlorperazine was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors.1,9The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well.10Compared to other phenothiazine derivatives, prochlorperazine is less sedating and has a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics.12Other than its primary action on D2 receptors, one study showed that prochlorperazine may inhibit the P2X7 receptor in human macrophages, leading to inhibition of calcium ion influx.9",CN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1,"The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its anti-dopaminergic effects. Prochlorperazine blocks the D dopamine receptors in the brain, which are somatodendritic autoreceptors. Inhibition of D receptor signaling results in the blockade of postsynaptic dopamine receptors in the mesolimbic systemand an increased dopamine turnover. Nausea and vomiting are proposed to arise from peripheral or central stimulation of serotonin type (-HT) and dopamine type receptors, the predominant receptors expressed at the chemoreceptor trigger zone (CTZ).,Prochlorperazine exerts antiemetic effects and was shown to inhibit apomorphine-induced vomiting by blocking D dopamine receptors in the CTZ..TargetActionsOrganismADopamine D receptorantagonistHumansUHistamine H receptorantagonistHumansUAlpha- adrenergic receptorsantagonistHumansNAlpha- adrenergic receptorsantagonistHumans",[],"['Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenothiazines', 'Phenothiazines With Piperazine Structure', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Schizophrenia', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB01092,Ouabain,"A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging ATPase.","['P05023', 'P50993', 'P13637']","Ouabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.",[H][C@@]12CC[C@]3(O)C[C@H](C[C@@H](O)[C@]3(CO)[C@@]1([H])[C@H](O)C[C@]1(C)[C@H](CC[C@]21O)C1=CC(=O)OC1)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O,"Ouabain inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Ouabain also acts on the electrical activity of the heart, increasing the slope of phase depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-inhibitorHumansUSodium/potassium-transporting ATPase subunit alpha-inhibitorHumansUSodium/potassium-transporting ATPase subunit alpha-inhibitorHumans",[],"['Carbohydrates', 'Cardanolides', 'Cardenolides', 'Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Glycosides', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'Protective Agents', 'Steroids', 'Strophanthins', 'Strophanthus Glycosides']" +DB00481,Raloxifene,Raloxifeneis a selective estrogen receptor modulator that is used to prevent and treat osteoporosis and reduce the risk of invasive breast cancer in high-risk postmenopausal women.,"['P03372', 'Q92731', 'P50453', 'P04155']","Raloxifene belongs to the selective estrogen receptor modulator (SERM) drug class that exhibits estrogenic effects on bone and lipid metabolism while mediating anti-estrogenic effects on uterine endometrium and breast tissues.7On skeletal tissues, raloxifene stimulates bone-depositing osteoblasts and inhibits bone-resorbing osteoclasts12to augument bone mineral density.7Raloxifene produces estrogen-like effects on bone, reducing the resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss.LabelIn three randomized, placebo-controlled trials in Europe, postmenopausal women receiving raloxifene at variable doses of 30 to 150 mg daily demonstrated significant increases in bone mineral density in the lumbar spine, total hip, femoral neck and total body compared to placebo.7In the MORE and RUTH trials, there were fewer incidences of vertebral fractures in postmeopausal women receiving raloxifene compared to placebo.6In a eight-week study evaluating short-term effects of raloxifene in healthy postmenopausal women, there was a decrease in the bone turnover markers, such as serum alkaline phosphatase level, serum osteocalcin level and urinary calcium excretion.7Raloxifene was shown to inhibit estrogen-dependent proliferation of human breast cancer cellsin vitroand development of induced mammary tumors in ratsin vivo.4In adult female rats, raloxifene produced a greater regression of the mammary gland thantamoxifen.4The MORE trial was a multicenter, randomized, double-blind clinical trial that investigated the long-term effects of the drug therapy in European and American postmenopausal women receiving raloxifene for 40 months.2Additionally, a reduction in the incidence of invasive breast cancer was also demonstrates in the CORE and RUTH trials.6Study findings demonstrated that compared to placebo, the risk of invasive breast cancer was decreased by 76% among postmenopausal women with osteoporosis. There was a decrease in the risk of estrogen receptor-positive breast cancer by 90% but there was no increase in the risk of endometrial cancer. Unlike hormone replacement therapy, raloxifene does not mediate proliferative or stimulatory effects on endometrial tissue. Findings from both animal and human studies demonstrated no significant changes in the histologic appearance of the endometrium.7Raloxifene promotes estrogen-like effects on lipid metabolism. In a European trial that evaluated lipid profiles following raloxifene therapy over the 24-month period, there were significant decreases in the serum concentrations of total and low-density lipoprotein (LDL) cholesterol over a 24-month period of raloxifene therapy.7Raloxifene is not associated with causing alterations in the serum levels of HDL cholesterol or triglycerides.7As the HDL choesterol level is considered a strong inverse predictor of cardiovascular disease in women, the cardioprotective effects of raloxifene were questioned. Due to limited data on the long-term trials, it is not possible to determine whether the small lipid effects produced by raloxifene correlate with a smaller degree of cardioprotective activity compared with hormone replacement therapy.7",OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2,"Raloxifene is a selective estrogen receptor modulator that acts as both an estrogen agonist and antagonist via differential effects on the tissue-specific estrogen receptors. Based on the findings of competitive binding assays, raloxifene displays binding affinity that is similar to that ofestradiol, the predominant circulating estrogen.Estrogens play variable roles at different tissues in females, including the bone, breasts, uterus and liver, by binding to the steroid nuclear hormone receptors, Estrogen Receptor alpha (ERα) or Estrogen Receptor beta (ERβ).These receptors are normally bound to the Heat Shock Protein (Hsp) when unbound to the ligand. Ligand binding induces a conformational change in the receptor that promotes dissociation of the receptor from Hsp, dimerization and translocation into the nucleus. This movement into the nucleus allows the receptor to bind to genomic locations based on sequence recognition of the DNA binding domain, also known as the Estrogen Response Elements (EREs).In bones, endogenous estrogens normally modulate multiple DNA response elements, including the gene-encoding transforming growth factor-β (TGF-β), which is a cytokine embedded in the bone matrix.TGF-β plays an important role in bone remodellingby working with other cytokines to induce production of osteoblasts, such as IL-, and attenuate the activity of osetoclasts. Estrogens typically maintain the bone integrity by inhibiting the cytokines that recruit osteoclasts and oppose the bone-resorbing, Ca+-mobilizing action of parathyroid hormone. In contrast, estrogens promote osteoblast proliferation, augment the production of TGF-β and bone morphogenic proteins, and inhibit apoptosis.Mimicking the action of endogenous estrogen in bone tissues, raloxifene binds to the estrogen receptor to influence gene transcription through interactions with the estrogen response element (ERE) and a distinct DNA target, the raloxifene response element (RRE).It occupies the same ER ligand binding site as estrogen.Upon binding, raloxifene induces a conformational change of the receptor, allowing mediation of direct binding to transcriptional elements by accessory proteins. Increased expression of bone matrix proteins, such as alkaline phosphatase, osteonectin, osteocalcin and collagen may be seen.The agonistic or antagonistic action of raloxifene depends on the extent of recruitment of coactivators and corepressors to estrogen receptor (ER) target gene promotors.LabelIn breast tissues, raloxifene acts as an estrogen receptor antagonist to attenuate the estrogen-dependent proliferative effects of epithelial cell expansion. In addition to the antiproliferative effects, raloxifene prevents the production of cytokines and recruitment of macrophages and lymphocytes into tumor mass.TargetActionsOrganismAEstrogen receptor alphaagonistHumansAEstrogen receptor betaagonistHumansUSerpin BNot AvailableHumansUTrefoil factor Not AvailableHumans",[],"['BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'Benzylidene Compounds', 'Bone Density Conservation Agents', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Estrogen Agonist-antagonists', 'Estrogen Agonist/Antagonist', 'Estrogen Antagonists', 'Estrogen Receptor Modulators', 'Genito Urinary System and Sex Hormones', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein substrates', 'Selective Estrogen Receptor Modulators', 'Sex Hormones and Modulators of the Genital System', 'Stilbenes', 'UGT1A1 Substrates']" +DB00929,Misoprostol,Misoprostolis a prostaglandin E1 analogue used to reduce the risk of NSAID-induced gastric ulcers and to terminate pregnancies.,"['P43115', 'P43116', 'P34995', 'P35408']","Misoprostol is a prostaglandin E1 analog used to reduce the risk of NSAID induced gastric ulcers by reducing secretion of gastric acid from parietal cells.3,13,14Misoprostol is also used to manage miscarriages and used alone or in combination with mifepristone for first trimester abortions.4,2,6An oral dose of misoprostol has an 8 minute onset of action and a duration of action of approximately 2 hours, a sublingual dose has an 11 minute onset of action and a duration of action of approximately 3 hours, a vaginal dose has a 20 minute onset of action and a duration of action of approximately 4 hours, and a rectal dose has a 100 minute onset of action and a duration of action of approximately 4 hours.7",CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC,Misoprostol is a synthetic prostaglandin E analog that stimulates prostaglandin E receptors on parietal cells in the stomach to reduce gastric acid secretion.Mucus and bicarbonate secretion are also increased along with thickening of the mucosal bilayer so the mucosa can generate new cells.Misoprostol binds to smooth muscle cells in the uterine lining to increase the strength and frequency of contractions as well as degrade collagen and reduce cervical tone.TargetActionsOrganismAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansUProstaglandin E receptor EP subtypeagonistHumans,"['Induction of cervix ripening therapy', 'Medically induced abortion']","['Abortifacient Agents', 'Abortifacient Agents, Nonsteroidal', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Autacoids', 'Biological Factors', 'Drugs causing inadvertant photosensitivity', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Gastrointestinal Agents', 'Genito Urinary System and Sex Hormones', 'Inflammation Mediators', 'Lipids', 'Musculo-Skeletal System', 'Photosensitizing Agents', 'Propionates', 'Prostaglandin E1 Analog', 'Prostaglandins', 'Prostaglandins E, Synthetic', 'Prostaglandins, Synthetic', 'Reproductive Control Agents', 'Uterotonic agents']" +DB06710,Methyltestosterone,"Methyltestosteroneis a synthetic anabolic steroid used for the replacement therapy in conditions associated with testosterone deficiencies in males, such as hypogonadism, and treatment of advancing inoperable metastatic breast cancer in females.","['P10275', 'P03372']","Testosterone is a steroid hormone from the androgen group. Testosterone is primarily secreted from the testes of males. In females, it is produced in the ovaries, adrenal glands and by conversion of adrostenedione in the periphery. It is the principal male sex hormone and an anabolic steroid. In both males and females, it plays key roles in health and well-being. Examples include enhanced libido, energy, immune function, and protection against osteoporosis. On average, the adult male body produces about twenty times the amount of testosterone than an adult female's body does.",[H][C@@]12CC[C@](C)(O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to α-dihydrotestosterone (DHT) by the cytoplasmic enzyme α-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about . times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.TargetActionsOrganismAAndrogen receptoragonistHumansUEstrogen receptor alphaNot AvailableHumans",[],"['3-Oxoandrosten (4) Derivatives', 'Anabolic Agents', 'Androgens', 'Androgens and Estrogens', 'Androstanes', 'Androstenes', 'Androstenols', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OAT3/SLC22A8 Inducers', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors']" +DB00295,Morphine,Morphineis an opioid agonist used for the relief of moderate to severe acute and chronic pain.,"['P35372', 'P41145', 'P41143', 'Q9Y6Y9']","Morphine binding to opioid receptors blocks transmission of nociceptive signals, signals pain-modulating neurons in the spinal cord, and inhibits primary afferent nociceptors to the dorsal horn sensory projection cells.1Morphine has a time to onset of 6-30 minutes.1Excess consumption of morphine and other opioids can lead to changes in synaptic neuroplasticity, including changes in neuron density, changes at postsynaptic sites, and changes at dendritic terminals.3Intravenous morphine's analgesic effect is sex dependent. The EC50in men is 76ng/mL and in women is 22ng/mL.5Morphine-6-glucuronide is 22 times less potent than morphine in eliciting pupil constriction.5",[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O,"Morphine--glucuronide is responsible for approximately % of the response observed by morphine administration.Morphine and its metabolites act as agonists of the mu and kappa opioid receptors.The mu-opioid receptor is integral to morphine's effects on the ventral tegmental area of the brain. Morphine's activation of the reward pathway is mediated by agonism of the delta-opioid receptor in the nucleus accumbens,while modification of the respiratory system and addiction disorder are mediated by agonism of the mu-opioid receptor.TargetActionsOrganismAMu-type opioid receptoragonistregulatorHumansAKappa-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansULymphocyte antigen activatorHumans",[],"['Alkaloids', 'Analgesics', 'Anesthetics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'High-risk opioids', 'Hypotensive Agents', 'Narcotics', 'Natural Opium Alkaloids', 'Nervous System', 'Neuraxial Anesthetics', 'Opiate Agonists', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB01783,Pantothenic acid,Pantothenic acidis a vitamin B5 found in various nutritional supplements.,['P0A6I3'],"Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate.Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively.Since pantothenic acid participates in a wide array of key biological roles, it may have numerous wide-ranging effects.",CC(C)(CO)[C@@H](O)C(=O)NCCC(O)=O,Pantothenic acid is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.TargetActionsOrganismUPantothenate kinaseNot AvailableEscherichia coli (strain K),['Nutritional supplementation'],"['Alanine', 'Alimentary Tract and Metabolism', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Blood Coagulation Factors', 'Cicatrizants', 'Dermatologicals', 'Imides', 'Micronutrients', 'Preparations for Treatment of Wounds and Ulcers', 'Vitamin B Complex', 'Vitamins']" +DB00928,Azacitidine,Azacitidineis a pyrimidine nucleoside analogue used to treat certain subtypes of myelodysplastic syndrome.,['P26358'],"The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis, and hypomethylation may restore normal function to genes critical for differentiation and proliferation.16Genome-wide DNA methylation levels in bone marrow granulocytes were reduced in patients with juvenile myelomonocytic leukemia after the first treatment cycle of azacitidine (75 mg/m2or 2.5 mg/kg), confirming the DNA-hypomethylating activity of azacitidine.16The use of azacitidine causes anemia, neutropenia and thrombocytopenia in adult patients with myelodysplastic syndrome and pediatric patients with juvenile myelomonocytic leukemia. Azacitidine may cause renal toxicity, tumor lysis syndrome and embryo-fetal toxicity. It may also lead to the development of hepatotoxicity in patients with severe pre-existing hepatic impairment.16",NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O,"Azacitidine (-azacytidine) is a chemical analogue of the cytosine nucleoside present in DNA and RNA.,It induces antineoplastic activity by inhibiting DNA methyltransferase at low doses and inducing cytotoxicity by incorporating itself into RNA and DNA at high doses.,,Covalent binding to DNA methyltransferase results in DNA hypomethylation and prevents DNA synthesis.On the other hand, the incorporation of azacitidine into RNA and DNA leads to cytotoxicity as follows: Following cellular uptake, azacitidine is phosphorylated by uridine-cytidine kinase to form -azacytidine monophosphate. Afterwards, pyrimidine monophosphate and diphosphate kinases phosphorylate -azacytidine monophosphate to form -azacytidine diphosphate and triphosphate, respectively. Azacitidine triphosphate is able to incorporate into RNA, disrupting RNA metabolism and protein synthesis. The reduction of azacytidine diphosphate leads to the formation of -aza-deoxycytidine diphosphate, which is then phosphorylated to form -azadeoxycitidine triphosphate, a compound able to incorporate into DNA and inhibit DNA synthesis.As a ribonucleoside, azacitidine incorporates into RNA to a larger extent than into DNA. Incorporating into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and the inhibition of protein production, resulting in cell death. During the S-phase of the cell cycle, azacitidine exhibits the highest toxicity; however, the predominant mechanism of cytotoxicity has not been elucidated.The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine. It is believed that azacitidine exerts its antineoplastic effects through direct cytotoxicity on abnormal hematopoietic cells in the bone marrow.TargetActionsOrganismADNA (cytosine-)-methyltransferase inhibitorHumansARNAotherHumansADNAotherHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Aza Compounds', 'Cytidine Deaminase Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'Pyrimidine Analogues', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Ribonucleosides', 'Toxic Actions']" +DB00822,Disulfiram,Disulfiramis a carbamate derivative used to treat alcohol addiction.,"['P09172', 'P05091']","Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to influence the rate of alcohol elimination from the body. Prolonged administration of disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol.",CCN(CC)C(=S)SSC(=S)N(CC)CC,"Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfiram blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase, which acts in the second step of ethanol utilization. In addition, disulfiram competitively binds and inhibits the peripheral benzodiazepine receptor, which may indicate some value in the treatment of the symptoms of alcohol withdrawal, however this activity has not been extensively studied.TargetActionsOrganismADopamine beta-hydroxylaseinhibitorHumansAAldehyde dehydrogenase, mitochondrialinhibitorHumans",[],"['Acetyl Aldehyde Dehydrogenase Inhibitors', 'Acids, Acyclic', 'Agents that reduce seizure threshold', 'Alcohol Deterrents', 'Aldehyde Dehydrogenase Inhibitor', 'Antiparasitic Products, Insecticides and Repellents', 'BSEP/ABCB11 Substrates', 'Carbamates', 'Central Nervous System Agents', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Disulfides', 'Drugs Used in Addictive Disorders', 'Drugs Used in Alcohol Dependence', 'Ectoparasiticides, Incl. Scabicides', 'Ectoparasiticides, Incl. Scabicides, Insecticides and Repellents', 'Enzyme Inhibitors', 'Nervous System', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfides', 'Sulfur Compounds', 'Sulfur Containing Products', 'Thiocarbamates']" +DB00586,Diclofenac,Diclofenacis an NSAID used to treat the signs and symptoms of osteoarthritis and rheumatoid arthritis.,"['P35354', 'P23219']","Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever.Label,17It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.",OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl,"Diclofenac inhibits cyclooxygenase- and -, the enzymes responsible for production of prostaglandin (PG) Gwhich is the precursor to other PGs.Label,These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac.PGEis the primary PG involved in modulation of nociception.It mediates peripheral sensitization through a variety of effects.,PGEactivates the Gq-coupled EPreceptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGEalso activates the EPreceptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member (TRPV) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the PX purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGEact via EPto increase sensitivity to bradykinin and via EPto further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EPreceptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGIis known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.PGIand PGEcontribute to acute inflammation via their IP and EPreceptors.,Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGEalso contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.PGDplays a role in the activation of endothelial cell release of cytokines through its DPreceptor.PGIand PGEmodulate T-helper cell activation and differentiation through IP, EP, and EPreceptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.PGEcan cross the blood-brain barrier and act on excitatory GqEPreceptors on thermoregulatory neurons in the hypothalamus.This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGEthereby reducing the activity of these neurons.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Acids, Carbocyclic', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antimigraine Agents, Miscellaneous', 'Antirheumatic Agents', 'BSEP/ABCB11 Substrates', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Cyclooxygenase-2 (COX-2) Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Prostaglandin Production', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Ethylamines', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'Ophthalmologicals', 'Other Nonsteroidal Anti-inflammatory Agents', 'P-glycoprotein inducers', 'Peripheral Nervous System Agents', 'Phenylacetates', 'Photosensitizing Agents', 'Sensory Organs', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain', 'UDP Glucuronosyltransferases Inhibitors', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B17 Inhibitors', 'UGT2B7 substrates']" +DB01097,Leflunomide,Leflunomideis a pyrimidine synthesis inhibitor indicated to treat rheumatoid arthritis.,"['Q02127', 'P35869', 'Q14289']","Leflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis.",CC1=C(C=NO1)C(=O)NC1=CC=C(C=C1)C(F)(F)F,"Leflunomide is a prodrug that is rapidly and almost completely metabolized following oral administration to its pharmacologically active metabolite, A . This metabolite is responsible for essentially all of the drug's activity in-vivo. The mechanism of action of leflunomide has not been fully determined, but appears to primarily involve regulation of autoimmune lymphocytes. It has been suggested that leflunomide exerts its immunomodulating effects by preventing the expansion of activated autoimmune lymphocytes via interferences with cell cycle progression. In-vitro data indicates that leflunomide interferes with cell cycle progression by inhibiting dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine ribonucleotide uridine monophosphate (rUMP)synthesis) and has antiproliferative activity. Human dihydroorotate dehydrogenase consists of domains: an α/β-barrel domain containing the active site and an α-helical domain that forms a tunnel leading to the active site. A binds to the hydrophobic tunnel at a site near the flavin mononucleotide. Inhibition of dihydroorotate dehydrogenase by A prevents production of rUMP by the de novo pathway; such inhibition leads to decreased rUMP levels, decreased DNA and RNA synthesis, inhibition of cell proliferation, and G cell cycle arrest. It is through this action that leflunomide inhibits autoimmune T-cell proliferation and production of autoantibodies by B cells. Since salvage pathways are expected to sustain cells arrested in the G phase, the activity of leflunomide is cytostatic rather than cytotoxic. Other effects that result from reduced rUMP levels include interference with adhesion of activated lymphocytes to the synovial vascular endothelial cells, and increased synthesis of immunosuppressive cytokines such as transforming growth factor-β (TGF-β). Leflunomide is also a tyrosine kinase inhibitor. Tyrosine kinases activate signalling pathways leading to DNA repair, apoptosis and cell proliferation. Inhibition of tyrosine kinases can help to treating cancer by preventing repair of tumor cells.TargetActionsOrganismADihydroorotate dehydrogenase (quinone), mitochondrialinhibitorHumansUAryl hydrocarbon receptoragonistHumansUProtein-tyrosine kinase -betaantagonistHumans",[],"['Adjuvants', 'Agents Causing Muscle Toxicity', 'Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Disease-modifying Antirheumatic Agents', 'Enzyme Inhibitors', 'Immunologic Factors', 'Immunosuppressive Agents', 'Isoxazoles', 'Selective Immunosuppressants']" +DB00514,Dextromethorphan,Dextromethorphanis an NMDA receptor antagonist used to treat cases of dry cough.,"['Q99720', 'Q8TCU5', 'Q15822', 'P31645', 'O00264', 'P32297', 'P43681', 'P30926', 'P17787', 'P36544', 'P35372', 'P41143', 'P41145', 'P04839', 'P13498', 'P14598', 'P19878', 'Q15080', 'P63000', 'P15153', 'P23975']","Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect.14,15,13It has a moderate therapeutic window, as intoxication can occur at higher doses.10Dextromethorphan has a moderate duration of action.13Patients should be counselled regarding the risk of intoxication.10",[H][C@]12CCCC[C@]11CCN(C)[C@H]2CC2=C1C=C(OC)C=C2,"Dextromethorphan is an agonist of NMDA and sigma- receptors.It is also an antagonist of α/β nicotinic receptors.However, the mechanism by which dextromethorphan's receptor agonism and antagonism translates to a clinical effect is not well understood.TargetActionsOrganismASigma non-opioid intracellular receptor agonistHumansAGlutamate receptor ionotropic, NMDA AantagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUSodium-dependent serotonin transporterinhibitorHumansUMembrane-associated progesterone receptor component binderHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit beta-antagonistHumansUNeuronal acetylcholine receptor subunit beta-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUMu-type opioid receptoragonistregulatorHumansUDelta-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumansUNADPH oxidaseinhibitorHumansUSodium-dependent noradrenaline transporterinhibitorHumans","['Airway secretion clearance therapy', 'Bronchodilation', 'Oropharyngeal antisepsis']","['Alkaloids', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antitussive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cough and Cold Preparations', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Excitatory Amino Acid Agents', 'Excitatory Amino Acid Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'NMDA Receptor Antagonists', 'Opiate Alkaloids', 'Opioids', 'Opium Alkaloids and Derivatives', 'Phenanthrenes', 'Respiratory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Sigma-1 Agonist', 'Sigma-1 Receptor Agonists', 'UGT2B17 substrates', 'UGT2B7 substrates', 'Uncompetitive N-methyl-D-aspartate Receptor Antagonist', 'Uncompetitive NMDA Receptor Antagonists']" +DB00619,Imatinib,"Imatinibis a tyrosine kinase inhibitor used to treat a number of leukemias, myelodysplastic/myeloproliferative disease, systemic mastocytosis, hypereosinophilic syndrome, dermatofibrosarcoma protuberans, and gastrointestinal stromal tumors.","['P11274', 'P10721', 'O43519', 'P04629', 'P07333', 'P16234', 'Q08345', 'P00519', 'P09619', 'Q16832']","Imatinib is a 2-phenylaminopyrimidine derivative neoplastic agent that belongs to the class of tyrosine kinase inhibitors.14Although imatinib inhibits a number of tyrosine kinases, it is quite selective toward the BCR-ABL fusion protein that is present in various cancers.10BCR-ABL pathway controls many downstream pathways that are heavily implicated in neoplastic growth such as the Ras/MapK pathway (cellular proliferation), Src/Pax/Fak/Rac pathway (cellular motility), and PI/PI3K/AKT/BCL-2 pathway (apoptosis pathway).7,8,9Therefore, the BCR-ABL pathway is an attractive target for cancer treatment. Although normal cells also depend on these pathways for growth, these cells tend to have redundant tyrosine kinases to continually function in spite of ABL inhibition from imatinib.1Cancer cells, on the other hand, can have a dependence on BCR-ABL, thus more heavily impacted by imatinib.1",CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1,"Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutively active tyrosine kinase created by the Philadelphia chromosome abnormality in CML.Although the function of normal BCR is still unclear, ABL activation is overexpressed in various tumors and is heavily implicated in cancer cells growth and survival.,Imatinib inhibits the BCR-ABL protein by binding to the ATP pocket in the active site, thus preventing downstream phosphorylation of target protein.Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor +(SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces +apoptosis in GIST cells, which express an activating c-Kit mutation.TargetActionsOrganismABreakpoint cluster region proteininhibitorHumansAMast/stem cell growth factor receptor KitantagonistHumansARET proto-oncogeneinhibitorHumansUHigh affinity nerve growth factor receptorantagonistHumansUMacrophage colony-stimulating factor receptorantagonistHumansAPlatelet-derived growth factor receptor alphaantagonistHumansUEpithelial discoidin domain-containing receptor antagonistHumansATyrosine-protein kinase ABLinhibitorHumansAPlatelet-derived growth factor receptor betaantagonistHumansUDiscoidin domain-containing receptor antagonistHumans",[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Bcr-Abl Tyrosine Kinase Inhibitors', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'BSEP/ABCB11 Substrates', 'Cancer immunotherapy', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Highest Risk QTc-Prolonging Agents', 'Immunosuppressive Agents', 'Immunotherapy', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'OATP1B3 substrates', 'OCT1 substrates', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Piperazines', 'Protein Kinase Inhibitors', 'Pyrimidines', 'QTc Prolonging Agents', 'Tyrosine Kinase Inhibitors', 'UDP Glucuronosyltransferases Inhibitors', 'UGT2B17 Inhibitors']" +DB09131,Cupric Chloride,"Cupric Chlorideis a transition metal found in a variety of supplements and vitamins, including intravenous solutions for total parenteral nutrition (TPN).","['P04070', 'P04080']","Copper is an essential nutrient which serves as a co factor for serum ceruloplasmin, an oxidase necessary for proper formation of the iron carrier protein, transferrin. Copper also helps maintain normal rates of red and white blood cell formation. Providing copper during Total Parenteral Nutrition helps prevent development of the following deficiency symptoms: Leukopenia, neutropenia, anemia, depressed ceruloplasmin levels, impaired transferrin formation, secondary iron deficiency and osteoporosis.",Cl[Cu]Cl,"The in vitro interaction of organic copper compounds with rat liver glutathione S-transferases was studied with reduced glutathione and -chloro-,-dinitrobenzene as substrates. Both organic and inorganic copper are spontaneously conjugated with glutathione, but interact with glutathione S-transferase by direct binding to these proteins.TargetActionsOrganismUVitamin K-dependent protein CNot AvailableHumansUCystatin-BNot AvailableHumans",['Total parenteral nutrition therapy'],"['Elements', 'Metals', 'Metals, Heavy', 'Transition Elements']" +DB00834,Mifepristone,"Mifepristoneis a cortisol receptor blocker used to treat Cushing's syndrome, and to terminate pregnancies up to 70 days gestation.","['P06401', 'P04150', 'P07288', 'O75469']","Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.",[H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C1=CC=C(C=C1)N(C)C)C1=C3CCC(=O)C=C3CC[C@@]21[H],"The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results.In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.TargetActionsOrganismAProgesterone receptorantagonistHumansAGlucocorticoid receptorantagonistHumansUProstate-specific antigenNot AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumans",['Medically induced abortion'],"['Abortifacient Agents', 'Abortifacient Agents, Steroidal', 'Adrenal Cortex Hormones', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Substrates', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Synthetic', 'Contraceptives, Postcoital', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Estranes', 'Estrenes', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Highest Risk QTc-Prolonging Agents', 'Hormonal Contraceptives for Systemic Use', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypoglycemia-Associated Agents', 'Luteolytic Agents', 'Menstruation-Inducing Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'Progestational Hormone Receptor Antagonists', 'Progesterone Receptor Modulators', 'Progestin Antagonist', 'QTc Prolonging Agents', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00917,Dinoprostone,Dinoprostoneis a prostaglandin used to induce labor or abortion as well as to treat nonmetastatic gestational trophoblastic disease.,"['P43116', 'P34995', 'P43115', 'P35408', 'Q9Y5Y4']","Dinoprostone is equivalent to prostaglandin E2 (PGE2). It stimulates labor and delivery by stimulating the uterine, and thus terminates pregnancy. Dinoprostone is also capable of stimulating the smooth muscle of the gastrointestinal tract of man. This activity may be responsible for the vomiting and/or diarrhea that is not uncommon when dinoprostone is used to terminate pregnancy.",CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O,"Dinoprostone administered intravaginally stimulates the myometrium of the gravid uterus to contract in a manner that is similar to the contractions seen in the term uterus during labor, resulting in the evacuation of the products of conception from the uterus. It is believed that dinoprostone exerts its uterine effects via direct myometrial stimulation, but the exact mechanism of action is unkown. Other suggested mechanisms include the regulation of cellular membrane calcium transport and of intracellular concentrations of cyclic ','-adenosine monophosphate. Dinoprostone also appears to produce local cervical effects including softening, effacement, and dilation. The exact mechanism of action for this effect is also unknown, but it has been suggested that this effect may be associated with collagen degradation caused by secretion of the enzyme collagenase as a partial response to locally administered dinoprostone.TargetActionsOrganismAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansUProstaglandin D receptor agonistHumans","['Induction of cervix ripening therapy', 'Medically induced abortion', 'Uterus evacuation']","['Autacoids', 'Biological Factors', 'Dinoprostone, antagonists & inhibitors', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Genito Urinary System and Sex Hormones', 'Inflammation Mediators', 'Lipids', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Substrates', 'OATP2B1/SLCO2B1 substrates', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Prostaglandins', 'Prostaglandins E', 'Prostaglandins, Synthetic', 'Reproductive Control Agents', 'Uterotonic agents']" +DB00331,Metformin,Metforminis a biguanide antihyperglycemic used in conjunction with diet and exercise for glycemic control in type 2 diabetes mellitus. It is also used off-label for insulin resistance in polycystic ovary syndrome (PCOS).,"['Q16134', 'Q9Y478', 'P21695']","General effectsInsulin is an important hormone that regulates blood glucose levels.19Type II diabetes is characterized by a decrease in sensitivity to insulin, resulting in elevations in blood glucose when the pancreas can no longer compensate. In patients diagnosed with type 2 diabetes, insulin is unable to exert adequate effects on tissues and cells (i.e. insulin resistance)19and insulin deficiency may also be present.21Metformin reduces hepatic production of glucose, decreases the intestinal absorption of glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization. In contrast with drugs of the sulfonylurea class, which lead to hyperinsulinemia, the secretion of insulin is unchanged with metformin use.23Effect on fasting plasma glucose (FPG) and Glycosylated hemoglobin (HbA1c)HbA1c is an important periodic measure of glycemic control used to monitor diabetic patients. Fasting plasma glucose is also a useful and important measure of glycemic control. In a 29-week clinical trial of subjects diagnosed with type II diabetes, metformin decreased the fasting plasma glucose levels by an average of 59 mg/dL from baseline, compared to an average increase of 6.3 mg/dL from baseline in subjects taking a placebo.23Glycosylated hemoglobin (HbA1c) was decreased by about 1.4% in subjects receiving metformin, and increased by 0.4% in subjects receiving placebo only.23",CN(C)C(=N)NC(N)=N,"Metformin's mechanisms of action are unique from other classes of oral antihyperglycemic drugs. Metformin decreases blood glucose levels by decreasing hepatic glucose production (also called gluconeogenesis), decreasing the intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilization.It is well established that metformin inhibits mitochondrial complex I activity, and it has since been generally postulated that its potent antidiabetic effects occur through this mechanism.,The above processes lead to a decrease in blood glucose, managing type II diabetes and exerting positive effects on glycemic control.After ingestion, the organic cation transporter- (OCT) is responsible for the uptake of metformin into hepatocytes (liver cells). As this drug is positively charged, it accumulates in cells and in the mitochondria because of the membrane potentials across the plasma membrane as well as the mitochondrial inner membrane. Metformin inhibits mitochondrial complex I, preventing the production of mitochondrial ATP leading to increased cytoplasmic ADP:ATP and AMP:ATP ratios.These changes activate AMP-activated protein kinase (AMPK), an enzyme that plays an important role in the regulation of glucose metabolism.Aside from this mechanism, AMPK can be activated by a lysosomal mechanism involving other activators. Following this process, increases in AMP:ATP ratio also inhibitfructose-,-bisphosphataseenzyme, resulting in the inhibition of gluconeogenesis, while also inhibitingadenylate cyclaseand decreasing the production of cyclic adenosine monophosphate (cAMP),a derivative of ATP used for cell signaling. Activated AMPK phosphorylates two isoforms of acetyl-CoA carboxylase enzyme, thereby inhibiting fat synthesis and leading to fat oxidation, reducing hepatic lipid stores and increasing liver sensitivity to insulin.In the intestines, metformin increases anaerobic glucose metabolism in enterocytes (intestinal cells), leading to reduced net glucose uptake and increased delivery of lactate to the liver. Recent studies have also implicated the gut as a primary site of action of metformin and suggest that the liver may not be as important for metformin action in patients with type diabetes. Some of the ways metformin may play a role on the intestines is by promoting the metabolism of glucose by increasing glucagon-like peptide I (GLP-) as well as increasing gut utilization of glucose.In addition to the above pathway, the mechanism of action of metformin may be explained by other ways, and its exact mechanism of action has been under extensive study in recent years.,,,TargetActionsOrganismAElectron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrialinhibitorHumansA'-AMP-activated protein kinase subunit beta-induceractivatorHumansUGlycerol--phosphate dehydrogenase [NAD(+)], cytoplasmicinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amidines', 'Biguanides', 'Blood Glucose Lowering Agents', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Guanidines', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Oral Hypoglycemics']" +DB00787,Acyclovir,"Acycloviris a guanosine analog used to treat herpes simplex, varicella zoster, herpes zoster.","['P04293', 'P09252']","Acyclovir is a nucleoside analog that inhibits the action of viral DNA polymerase and DNA replication of different herpesvirus.10,11,12,13,14,15Acyclovir has a wide therapeutic window as overdose is rare in otherwise healthy patients.11",NC1=NC(=O)C2=C(N1)N(COCCO)C=N2,"Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase.Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase.,Acyclovir triphosphate has higher affinity for viral DNA polymerase than cellular DNA polymerase and incorporates into the DNA where the missing ' and ' carbons causes DNA chain termination.In other cases acyclovir triphosphate competes so strongly for viral DNA polymerase that other bases cannot associate with the enzyme, inactivating it.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-ADNA polymerase catalytic subunitinhibitorHHV-",[],"['Acyclovir and prodrug', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor', 'Herpes Zoster Virus Nucleoside Analog DNA Polymerase Inhibitor', 'Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'Nephrotoxic agents', 'Nucleic Acid Synthesis Inhibitors', 'Nucleosides and Nucleotides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OCT1 inhibitors', 'OCT1 substrates', 'Ophthalmologicals', 'Purines', 'Purinones', 'Sensory Organs']" +DB00203,Sildenafil,Sildenafilis a phosphodiesterase inhibitor used for the treatment of erectile dysfunction.,"['O76074', 'P18545', 'Q13956', 'P11926', 'Q9NZQ7']","In vitro studies have shown that sildenafil is selective for phosphodiesterase-5 (PDE5)11,12,13,14,15,16,8,9. Its effect is more potent on PDE5 than on other known phosphodiesterases11,12,13,14,15,16,8,9. In particular, there is a 10-times selectivity over PDE6 which is involved in the phototransduction pathway in the retina11,12,13,14,15,16,8,9. There is an 80-times selectivity over PDE1, and over 700-times over PDE 2, 3, 4, 7, 8, 9, 10 and 1111,12,13,14,15,16,8,9. And finally, sildenafil has greater than 4,000-times selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility11,12,13,14,15,16,8,9.In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (via the use of RigiScan®), after sildenafil administration compared with placebo11,12,13,14,15,16,8,9. Most studies assessed the efficacy of sildenafil approximately 60 minutes post-dose11,12,13,14,15,16,8,9. The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration11,12,13,14,15,16,8,9. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours11,12,13,14,15,16,8,9.Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects11,12,13,14,15,16,8,9. After chronic dosing of 80 mg, three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mmHg respectively11,12,13,14,15,16,8,9. After chronic dosing of 80 mg, three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg)11,12,13,14,15,16,8,9. At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen11,12,13,14,15,16,8,9.Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG11,12,13,14,15,16,8,9. After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported either11,12,13,14,15,16,8,9.In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70 % stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7 % and 6 % respectively compared to baseline11,12,13,14,15,16,8,9. Mean pulmonary systolic blood pressure decreased by 9%11,12,13,14,15,16,8,9. Sildenafil showed no effect on cardiac output and did not impair blood flow through the stenosed coronary arteries11,12,13,14,15,16,8,9.Mild and transient differences in color discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose11,12,13,14,15,16,8,9. The postulated mechanism for this change in color discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina11,12,13,14,15,16,8,9. Sildenafil has no effect on visual acuity or contrast sensitivity. In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n = 9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (which included visual acuity, Amsler grid, color discrimination simulated traffic light, and the Humphrey perimeter and photostress test)11,12,13,14,15,16,8,9.",CCCC1=NN(C)C2=C1N=C(NC2=O)C1=CC(=CC=C1OCC)S(=O)(=O)N1CCN(C)CC1,"Sildenafil is an oral therapy for erectile dysfunction,,,,. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis,,,,.The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation,,,,. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood,,,,.Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type (PDE) in the corpus cavernosum, where PDE is responsible for degradation of cGMP,,,,. Sildenafil has a peripheral site of action on erections,,,,. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue,,,,. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE by sildenafil results in increased corpus cavernosum levels of cGMP,,,,. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects,,,,.Moreover, apart from the presence of PDE in the corpus cavernosum of the penis, PDE is also present in the pulmonary vasculature,,,,. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation,,,,. In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation,,,,.TargetActionsOrganismAcGMP-specific ','-cyclic phosphodiesteraseinhibitorHumansNRetinal rod rhodopsin-sensitive cGMP ','-cyclic phosphodiesterase subunit gammainhibitorHumansNRetinal cone rhodopsin-sensitive cGMP ','-cyclic phosphodiesterase subunit gammainhibitorHumansUOrnithine decarboxylasedownregulatorHumansUProgrammed cell death ligand downregulatorHumans",[],"['Agents Causing Muscle Toxicity', 'Amides', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Erectile Dysfunction', 'Enzyme Inhibitors', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Piperazines', 'Purines', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Urological Agents', 'Urologicals', 'Vasodilating Agents']" +DB00378,Dydrogesterone,"Dydrogesteroneis a synthetic progesterone for menstrual cycle regulation, infertility treatment, prevention of miscarriage, and other conditions.",['P06401'],"Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.",[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@]1([H])[C@@]2([H])C=CC2=CC(=O)CC[C@@]12C,Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus.TargetActionsOrganismAProgesterone receptoragonistHumans,"['Assisted Reproductive Technology therapy', 'Menstrual Regulation']","['Adrenal Cortex Hormones', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Pregnadien Derivatives', 'Pregnadienes', 'Pregnanes', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00396,Progesterone,"Progesteroneis a hormone used for a variety of functions, including contraception, control of abnormal uterine bleeding, maintenance of pregnancy, and prevention of endometrial hyperplasia.","['P06401', 'P08235', 'P03372', 'P05093', 'P41145', 'P02763', 'P04150', 'P10275', 'P04278', 'Q92731']","Progesterone, depending on concentration and dosage form, and timing of exposure may have several pharmacodynamic effects. These actions, according, to various preparations, are listed below:General effectsProgesterone is the main hormone of the corpus luteum and the placenta. It acts on the uterus by changing the proliferative phase to the secretory phase of the endometrium (inner mucous lining of the uterus). This hormone, stimulated by a hormone calledluteinizing hormone(LH) is the main hormone during the secretory phase to prepare the corpus luteum and the endometrium for implantation of a fertilized ovum. As the luteal phase concludes, the progesterone hormone sends negative feedback to the anterior pituitary gland in the brain to decrease FSH (follicle stimulating hormone) and LH (luteinizing hormone) levels. This prevents ovulation and maturation of oocytes (immature egg cells). The endometrium then prepares for pregnancy by increasing its vascularity (blood vessels) and stimulating mucous secretion. This process occurs by progesterone stimulating the endometrium to decrease endometrial proliferation, leading to a decreased uterine lining thickness, developing more complex uterine glands, collecting energy in the form of glycogen, and providing more uterine blood vessel surface area suitable for supporting a growing embryo. As opposed to cervical mucous changes observed during the proliferative phase and ovulation, progesterone decreases and thickens the cervical mucus, rendering it less elastic. This change occurs because the fertilization time period has passed, and a specific consistency of mucous amenable to sperm entry is no longer required16.Gelatinized capsulesProgesterone capsules are an oral dosage form of micronized progesterone which, chemically identical to progesterone of ovarian origin. Progesterone capsules have all the properties of endogenous progesterone with induction of a secretory phase endometrium with gestagenic, antiestrogenic, slightly antiandrogenic and anti-aldosterone effects24. Progesterone opposes the effects of estrogen on the uterus, and is beneficial in women with unopposed estrogen exposure, which carries an increased risk of malignancy24.Vaginal gel and vaginal insertThe gel preparation mimics the effects of naturally occurring progesterone. In the presence of adequate levels of estrogen, progesterone converts a proliferative endometrium into secretory endometrium. This means that the endometrium changes from a growing and thickening stage into a subsequent preparation stage for pregnancy, which involves further preparatory changes. Progesterone is necessary for the development of decidual tissue (specialized tissue amenable to supporting a possible pregnancy). Progesterone is required to increase endometrial receptivity for the implantation of a fertilized embryo. Once an embryo is implanted, progesterone helps to maintain the pregnancy20.Injection (intramuscular)Intramuscularly injected progesterone increases serum progesterone and aids in the prevention of endometrial tissue overgrowth due to unopposed estrogen (which leads to abnormal uterine bleeding and sometimes uterine cancer)18,25. In the absence or deficiency of progesterone, the endometrium continually proliferates, eventually outgrowing its limited blood supply, shedding incompletely, and leading to abnormal and/or profuse bleeding as well as malignancy18.Tablets, contraceptiveProgesterone-only contraceptive tablets prevent conception by suppressing ovulation in about half of users, causing a thickening of cervical mucus to inhibit sperm movement, lowering the midcycle LH and FSH hormone peaks, slowing the movement of the ovum through the fallopian tubes, and causing secretory changes in the endometrium as described above22.",[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"Progesterone binds and activates its nuclear receptor,PR, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy.Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy.Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately .%. The typical failure rate, however, is estimated to be approximately %, due to late or missed pills.TargetActionsOrganismAProgesterone receptoragonistHumansAMineralocorticoid receptorantagonistagonistHumansUEstrogen receptor alphaagonistinhibitordownregulatorHumansUSteroid -alpha-hydroxylase/, lyasesubstrateinhibitorHumansUKappa-type opioid receptoractivatorpotentiatorHumansUAlpha--acid glycoprotein binderHumansUGlucocorticoid receptorpartial agonistHumansUAndrogen receptoragonistpotentiatorHumansUSex hormone-binding globulinbinderpotentiatorHumansUEstrogen receptor betaagonistdownregulatorHumans",['Assisted Reproductive Technology therapy'],"['Adrenal Cortex Hormones', 'BCRP/ABCG2 Inducers', 'BCRP/ABCG2 Inhibitors', 'BSEP/ABCB11 Inhibitors', 'Corpus Luteum Hormones', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inducers', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Progesterone and Derivatives', 'Progesterone, antagonists & inhibitors', 'Progestin-containing Intrauterine Device', 'Progestins', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00477,Chlorpromazine,"Chlorpromazineis a phenothiazine antipsychotic used to treat nausea, vomiting, preoperative anxiety, schizophrenia, bipolar disorder, and severe behavioral problems in children.","['P14416', 'P21728', 'P08908', 'P28223', 'P35348', 'P35368', 'P35367', 'Q12809', 'P21728', 'P21918', 'P35462', 'P21917', 'P21918', 'P28335', 'P28223', 'P41595', 'P28335', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P11229', 'P20309', 'P17405', 'P0DP23', 'P02763', 'P19652', 'P50406', 'P34969', 'Q9H3N8']",Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.,CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(Cl)C=C2,"Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D, D, D and D - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (-HT and -HT, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha/alpha-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M/M-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). +Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use).TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor AantagonistHumansAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAHistamine H receptorantagonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUD() dopamine receptorinhibitorHumansUDopamine D receptorinhibitorHumansUDopamine D receptorbinderHumansUDopamine D receptorinhibitorHumansU-hydroxytryptamine receptor CbinderHumansU-hydroxytryptamine receptorbinderHumansUAlpha- adrenergic receptorsinhibitorHumansUAlpha- adrenergic receptorsinhibitorHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUSphingomyelin phosphodiesteraseinhibitorHumansUCalmodulininhibitorHumansUalpha-acid glycoproteinbinderHumansU-hydroxytryptamine receptor binderHumansU-hydroxytryptamine receptor binderHumansUHistamine H receptorbinderHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Autonomic Agents', 'BSEP/ABCB11 Inhibitors', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenothiazines', 'Phenothiazines With Aliphatic Side-Chain', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB00578,Carbenicillin,Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function.,"['P0AEB2', 'P24228', 'P08506', 'P02918', 'P02919', 'P0AD65', 'P0AD68', 'Q47066']","Carbenicillin is a semisynthetic penicillin. Though carbenicillin provides substantialin vitroactivity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, carbenicillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of:Escherichia coli,Proteus mirabilis,Proteus vulgaris,Morganella morganii,Pseudomonasspecies,Providencia rettgeri,Enterobacterspecies, andEnterococci(S. faecalis).",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C(C(O)=O)C1=CC=CC=C1)C(O)=O,"Free carbenicillin is the predominant pharmacologically active fraction of the salt. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria. Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that carbenicillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding proteininhibitorGram positive and gram negative bacteriaUBeta-lactamase Toho-substrateEscherichia coli",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 inhibitors', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00607,Nafcillin,Nafcillinis a penicillin derivative antibiotic used to treat susceptible staphylococcal infections.,"['Q7CRA4', 'P0A3M6', 'Q8DNB6', 'Q75Y35', 'Q8DR59']",Nafcillin is a semisynthetic antibiotic substance derived from 6-amino-penicillanic acid. The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and non penicillinase-producing strains of Staphylococcus species.,[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(OCC)C=CC2=CC=CC=C12)C(O)=O,"Like other penicillins, nafcillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication in the bacterial cell wall synthesisLabel. It inhibits the biosynthesis of the bacterial cell wall by forming covalent bonds with penicillin-binding proteins that play a critical role in the final transpeptidation process. Binding to penicillin-binding proteins inhibits the transpeptidase and carboxypeptidase activities conferred by these proteins and prevents the formation of the crosslinks.TargetActionsOrganismAPenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Resistant Penicillins', 'beta-Lactams', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 inhibitors', 'Penicillins', 'Sulfur Compounds']" +DB00415,Ampicillin,Ampicillinis a penicillin derivative used for the treatment of a variety of infections caused by gram-positive and gram-negative bacteria as well as some anaerobes.,"['Q8DNB6', 'Q7CRA4', 'Q75Y35', 'Q8DR59', 'P0A3M6', 'P46059', 'Q16348', 'Q02763']","Ampicillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name ""penicillin"" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Ampicillin hasin vitroactivity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ampicillin results from the inhibition of cell wall synthesis and is mediated through Ampicillin binding to penicillin binding proteins (PBPs). Ampicillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, Ampicillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Ampicillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)USolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUAngiopoietin- receptorNot AvailableHumans",[],"['Amides', 'Aminopenicillins', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Ophthalmologicals', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sensory Organs', 'Sulfur Compounds']" +DB00537,Ciprofloxacin,Ciprofloxacinis a second generation fluoroquinolone used to treat various susceptible bacterial infections.,"['P43702', 'P43700', 'P11388', 'Q12809', 'P0AES4', 'P0C1U9', 'Q59192', 'P05653', 'C3T8E2', 'B4YQT9', 'P20831']","Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria.9,18,19,20,21,22,23,24,25,26It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV.12Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase.13There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective.13Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.12",OC(=O)C1=CN(C2CC2)C2=CC(N3CCNCC3)=C(F)C=C2C1=O,"Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV.Ciprofloxacin's targeting of the alpha subunits of DNA gyrase prevents it from supercoiling the bacterial DNA which prevents DNA replication.,TargetActionsOrganismADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumansUPotassium voltage-gated channel subfamily H member Not AvailableHumansUDNA gyrase subunit ANot AvailableEscherichia coli (strain K)UDNA topoisomerase subunit ANot AvailableStaphylococcus aureusUDNA topoisomerase subunit BNot AvailableBacillus subtilis (strain )UDNA gyrase subunit ANot AvailableBacillus subtilis (strain )UMultidrug resistance protein MdtKNot AvailableEscherichia coliUGyrase ANot AvailableMycobacterium tuberculosisUDNA gyrase subunit ANot AvailableStaphylococcus aureus",[],"['Agents Causing Muscle Toxicity', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Fluoroquinolone Antibacterial', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 2 Inhibitors', 'MATE inhibitors', 'MATE substrates', 'Moderate Risk QTc-Prolonging Agents', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Otologicals', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Sensory Organs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00355,Aztreonam,Aztreonamis a beta-lactam antibiotic used to treat select aztreonam sensitive gram negative bacteria.,"['P42971', 'P05193', 'Q47066']","Aztreonam is a monocyclic beta-lactam antibiotic (a monobactam) originally isolated fromChromobacterium violaceum. Aztreonam exhibits potent and specific activity in vitro against a wide spectrum of gram-negative aerobic pathogens includingPseudomonas aeruginosa. It has no useful activity against gram-positive bacteria or anaerobes, but has very broad spectrum against gram-negative aerobes, includingPseudomonas aeruginosa. This has given it the nickname ""the magic bullet for aerobic gram-negative bacteria"". Aztreonam, unlike the majority of beta-lactam antibiotics, does not induce beta-lactamase activity and its molecular structure confers a high degree of resistance to hydrolysis by beta-lactamases (such as penicillinases and cephalosporinases) produced by most gram-negative and gram-positive pathogens; it is, therefore, usually active against gram-negative aerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases. It is active against many strains that are multiply-resistant to other antibiotics, such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonam maintains its antimicrobial activity over a pH range of 6 to 8 in vitro, as well as in the presence of human serum and under anaerobic conditions.",C[C@H]1[C@H](NC(=O)C(=N/OC(C)(C)C(=O)O)\C2=CSC([NH3+])=N2)C(=O)N1S([O-])(=O)=O,"The bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam for penicillin binding protein (PBP). By binding to PBP, aztreonam inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that aztreonam interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorBacillus subtilis (strain )ABeta-lactamasepotentiatorCitrobacter freundiiUBeta-lactamase Toho-substrateEscherichia coli",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Monobactam Antibacterial', 'Monobactams', 'Sulfur Compounds']" +DB09121,Aurothioglucose,Aurothioglucoseis a gold compound used in the treatment of rheumatoid arthritis.,"['Q08828', 'Q08462', 'O95622']","After administration, patient serum levels of gold rise sharply but decline over the following week6. Peak levels with aqueous preparations are higher and decline faster than those with oily preparations6. Regular weekly administration produces a continuous rise in the basal value for several months, after which the serum level becomes relatively stable6. After a standard weekly dose, considerable individual variation in the levels of gold can be observed6. A steady decline in gold levels occurs when the interval between injections is lengthened, and small amounts may be found in the serum for months after discontinuation of therapy6. The incidence of toxic reactions is seemingly unrelated to the plasma level of gold, but may perhaps be more associated with the total cumulative content of gold in the body6.",OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O,"Rheumatoid arthritis is an autoimmune disease in which the body's immune system mistakenly attacks the lining of various skeletal bone joints of the body,. These attacks are facilitated by various pro-inflammatory immune cells and agents like cytokines, histamines, mast cells, macrophages, monocytes, lymphocytes, leukocytes, and many others. The longterm result of this unwanted immune response is chronic inflammation and painful tissue damage,. The cause of the malfunctioning immune system in rheumatoid arthritis is unknown and there is no definitive cure for the condition,.Similarly, the mechanism of action of aurothioglucose is also not well elucidated. Nevertheless, some studies have suggested that the combination of both the sulfhydryl ligand and aureus cation present in aurothioglucose elicits an inhibitory effect on adenylyl cyclase activity in human lymphocyte membranes and in membranes of T and B lymphocyte subsets. In particular, such inhibition of the activity of adenylyl cyclase and its various isoforms would theoretically also limit the cyclases' ability to induce mast cell degranulation and histamine release, to enhance respiratory burst effects, to stimulate the action of resting macrophages, to induce and activate phagocytes, to induce neutrophil chemotaxis, etc. - all of which are pro-inflammatory actions.TargetActionsOrganismUAdenylate cyclase type Not AvailableHumansUAdenylate cyclase type Not AvailableHumansUAdenylate cyclase type Not AvailableHumans",[],"['Antiinflammatory and Antirheumatic Products', 'Antirheumatic Agents', 'Drugs that are Mainly Renally Excreted', 'Gold Preparations', 'Musculo-Skeletal System', 'Organogold Compounds', 'Organometallic Compounds', 'Specific Antirheumatic Agents']" +DB03783,Phenacetin,Phenacetin was withdrawn from the Canadian market in June 1973 due to concerns regarding nephropathy (damage to or disease of the kidney).,['P23219'],"Phenacetin was the first NSAID and fever reducer to go on the market. It acts as an analgesic at the spinal cord as well as a negative inotrope at the heart. It can be used to treat subacute rheumatoid arthritis, intercostal neuralgia, and ataxias.",CCOC1=CC=C(NC(C)=O)C=C1,TargetActionsOrganismUProstaglandin G/H synthase Not AvailableHumans,[],"['Acetanilides', 'Amides', 'Amines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anilides', 'Aniline Compounds', 'Central Nervous System Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Nervous System', 'OAT1/SLC22A6 inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB00274,Cefmetazole,Cefmetazoleis a cephalosporin antibiotic used to treat a variety of bacterial infections.,"['C1KC03', 'P02918', 'P02919', 'P0AD68', 'P0AEB2', 'P08506']","Cefmetazole is a second-generation cephalosporin. The cephalosporins are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillins. Cefmetazole is more active than 1st-generation cephalosporins against indole-positiveProteus,Serratia, anaerobic gram-negative bacilli (includingB. fragilis), and someE. coli,Klebsiella, andP. mirabilis, but is less active than cefoxitin or cefotetan against most gram-negative bacilli.",[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@]2(NC(=O)CSCC#N)OC)C(O)=O,The bactericidal activity of cefmetazole results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).TargetActionsOrganismAPenicillin binding protein ainhibitorStaphylococcus aureusAPenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacAinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacCinhibitorEscherichia coli (strain K),[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Cephamycins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB01069,Promethazine,"Promethazineis a first-generation antihistamine used for the treatment of allergic conditions, nausea and vomiting, and motion sickness.","['P35367', 'P14416', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P0DP23', 'P25021', 'Q99677', 'P43657', 'P51575', 'Q9UBL9', 'P56373', 'Q99571', 'Q93086', 'O15547', 'Q99572', 'P47900', 'Q96G91', 'Q9H244', 'Q9BPV8', 'Q15391', 'P41231', 'P51582', 'Q86VZ1', 'O00398', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q09470', 'Q16322', 'P16389', 'P22001', 'P22459', 'P22460', 'P17658', 'Q14721', 'Q92953', 'P48547', 'Q96PR1', 'Q14003', 'Q03721', 'Q9NSA2', 'Q9NZV8', 'Q9UK17', 'P15382', 'Q9Y6J6', 'Q9Y6H6', 'Q8WWG9', 'Q9UJ90', 'Q9H3M0', 'Q9UIX4', 'Q9UJ96', 'Q8TAE7', 'Q8TDN1', 'O95259', 'Q12809', 'Q9ULD8', 'Q9UQ05', 'Q8NCM2', 'Q9H252', 'Q9NS40', 'Q96L42', 'P51787', 'O43526', 'O43525', 'P56696', 'Q9NR82', 'Q96KK3', 'Q9BQ31', 'Q6PIU1', 'Q8TDN2', 'Q14722', 'Q13303']","Promethazine is is a histamine H1 antagonist that can be used for it's ability to induce sedation, reduce pain, and treat allergic reactions.12Promethazine's effects generally last 4-6h but can last up to 12h.12Patients should be counselled regarding CNS and respiratory depression, reduce seizure threshold, and bone marrow depression.12",CC(CN1C2=CC=CC=C2SC2=CC=CC=C12)N(C)C,"Promethazine is a an antagonist of histamine H, post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors.,,The antihistamine action is used to treat allergic reactions.Antagonism of muscarinic and NMDA receptors contribute to its use as a sleep aid, as well as for anxiety and tension.Antagonism of histamine H, muscarinic, and dopamine receptors in the medullary vomiting center make promethazine useful in the treatment of nausea and vomiting.TargetActionsOrganismAHistamine H receptorantagonistHumansUDopamine D receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUAlpha adrenergic receptorantagonistHumansUCalmodulininhibitorHumansUHistamine H receptorantagonistHumansUP PurinoceptorsinhibitorUVoltage-gated sodium channel alpha subunitinhibitorHumansUVoltage-gated Potassium Channelsinducer","['Sedative therapy', 'Adjunct to anesthesia and analgesia therapy']","['Acid Reducers', 'Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Amines', 'Anti-Allergic Agents', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidotes', 'Antihistamines for Systemic Use', 'Antihistamines for Topical Use', 'Antipruritics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Antipsychotic Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H2 Antagonists', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Muscarinic Antagonists', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Phenothiazine Derivatives', 'Phenothiazines', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Propylamines', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Sulfur Compounds']" +DB00322,Floxuridine,Floxuridineis an antimetabolite used as palliative management for liver metastases of gastrointestinal malignancy.,['P04818'],"Floxuridine is an anti-metabolite or a pyrimidine analog that works by disrupting the process S-phase of cell division, selectively targeting rapidly dividing cells. Due to the structural similarities, antimetabolites act as pyrimidine-like molecules and prevent normal pyrimidines from being incorporated into DNA. After successful biotransformation, floxuridine is converted into an active component, flurouracil, which blocks the enzyme which converts cytosine nucleosides into the deoxy derivative. Flurouracil also physically prevents the incorporation of thymidine nucleotides into the DNA strand by taking their place, further preventing DNA synthesis.",OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(F)C(=O)NC1=O,"Floxuridine rapidly undergoes catabolism to form -fluorouracil, which is the active component of the drug. -Fluorouracil primarily works by interfering with DNA synthesis; however, it may also inhibit the formation of fraudulent RNA via physical incorporation into the RNA. It is also an inhibitor of riboside phophorylase, preventing the utilization of pre-formed uracil in RNA synthesis. Floxuridine can also form -fluoro-'-deoxyuridine-'-phosphate (FUDR-MP), which is the monophosphate of floxuridine that inhibits thymidylate synthetase that plays a role in the methylation of deoxyuridylic acid to thymidylic acid during DNA synthesis. FUDR-MP thus interferes with DNA synthesis.TargetActionsOrganismAThymidylate synthaseNot AvailableHumans",['Palliative Treatment'],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Deoxyribonucleosides', 'Deoxyuridine', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Pyrimidine Analogues', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Thyroxine-binding globulin inducers', 'Toxic Actions']" +DB01603,Meticillin,One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection.,"['Q53707', 'Q8DNB6', 'Q7CRA4', 'P0A3M6', 'Q75Y35', 'Q8DR59']","Meticillin (INN, BAN) or methicillin (USAN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is no longer clinically used. Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the term methicillin-resistantStaphylococcus aureus(MRSA) continues to be used to describeStaphylococcus aureusstrains resistant to all penicillins.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(OC)C=CC=C1OC)C(O)=O,"Similar to other beta-lactam antimicrobials, meticillin blocks synthesis of the bacterial cell wall. Meticillin stops cross-linkage between the peptidoglycan polymer chains, which make up a large portion of gram-positive bacterial cell walls. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis.TargetActionsOrganismAMecA PBP' (penicillin binding protein ')inhibitorStaphylococcus aureusAPenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Resistant Penicillins', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Sulfur Compounds']" +DB00456,Cefalotin,"Cefalotinis a broad-spectrum cephalosporin antibiotic used for the treatment of serious bacterial infections in various locations, such as the urinary tract, skin, bone, and lower respiratory tract.","['P15555', 'Q8DR59', 'Q7CRA4', 'Q75Y35', 'Q8DNB6', 'P0A3M6', 'Q8XJ01', 'P00811']",Cefalotin (INN) or cephalothin (USAN) is a semisynthetic first generation cephalosporin having a broad spectrum of antibiotic activity that is administered parenterally.,[H][C@@]1(NC(=O)CC2=CC=CS2)C(=O)N2C(C(O)=O)=C(COC(C)=O)CS[C@]12[H],"The bactericidal activity of cefalotin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). The PBPs are transpeptidases which are vital in peptidoglycan biosynthesis. Therefore, their inhibition prevents this vital cell wall compenent from being properly synthesized.TargetActionsOrganismAD-alanyl-D-alanine carboxypeptidaseinhibitorStreptomyces sp. (strain R)APenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)ABeta-lactamasepotentiatorEscherichia coli (strain K)",[],"['Agents that reduce seizure threshold', 'Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'First-Generation Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Sulfur Compounds', 'Thiazines']" +DB00921,Buprenorphine,Buprenorphineis a partial opioid agonist used for management of severe pain that is not responsive to alternative treatments. Also used for maintenance treatment of opioid addiction.,"['P41145', 'P35372', 'P41143', 'P41146']","Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.DependenceBuprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Buprenorphine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion.[F4718]WithdrawalAbrupt discontinuation of treatment is not recommended as it may result in an opioid withdrawal syndrome that may be delayed in onset. Signs and symptoms may include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.[F4718]Risk of Respiratory and Central Nervous System (CNS) Depression and OverdoseBuprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressant, including alcohol. Use buprenorphine and naloxone sublingual tablets with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).22Risk of Overdose in Opioid Naïve PatientsThere have been reported deaths of opioid-naïve individuals who received a 2 mg dose of buprenorphine as a sublingual tablet for analgesia. Buprenorphine and naloxone sublingual tablets are not appropriate as an analgesic in opioid-naïve patients.22Precipitation of Opioid Withdrawal Signs and SymptomsIf buprenorphine is started in opioid-dependent individuals, it will displace the other opioids and cause a phenomenon known as ""precipitated withdrawal"" which is characterized by a rapid and intense onset of withdrawal symptoms. Individuals must therefore be in a state of mild to moderate withdrawal before starting therapy with buprenorphine.Because it contains naloxone, buprenorphine and naloxone sublingual tablets are also highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone.22Gastrointestinal EffectsBuprenorphine and other morphine-like opioids have been shown to decrease bowel motility and cause constipation. Buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions and should be administered with caution to patients with dysfunction of the biliary tract.22Effects on the Endocrine SystemOpioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.22Adrenal InsufficiencyCases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.22Use in Patients With Impaired Hepatic FunctionBuprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. The doses of buprenorphine and naloxone in this fixed-dose combination product cannot be individually titrated, and hepatic impairment results in a reduced clearance of naloxone to a much greater extent than buprenorphine. Therefore, patients with severe hepatic impairment will be exposed to substantially higher levels of naloxone than patients with normal hepatic function. This may result in an increased risk of precipitated withdrawal at the beginning of treatment (induction) and may interfere with buprenorphine’s efficacy throughout treatment. In patients with moderate hepatic impairment, the differential reduction of naloxone clearance compared to buprenorphine clearance is not as great as in subjects with severe hepatic impairment. However, buprenorphine/naloxone products are not recommended for initiation of (treatment induction) in patients with moderate hepatic impairment due to the increased risk of precipitated withdrawal. Buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate hepatic impairment who have initiated treatment on a buprenorphine product without naloxone. However, patients should be carefully monitored and consideration given to the possibility of naloxone interfering with buprenorphine’s efficacy.22Risk of Hepatitis, Hepatic EventsCases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, buprenorphine and naloxone sublingual tablets may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated.22Orthostatic HypotensionLike other opioids, buprenorphine and naloxone sublingual tablets may produce orthostatic hypotension in ambulatory patients.Elevation of Cerebrospinal Fluid PressureBuprenorphine, like other opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation.Elevation of Intracholedochal PressureBuprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract.",CO[C@]12CC[C@@]3(C[C@@H]1[C@](C)(O)C(C)(C)C)[C@H]1CC4=C5C(O[C@@H]2[C@@]35CCN1CC1CC1)=C(O)C=C4,"Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. It demonstrates a high affinity for the mu-opioid receptor but has lower intrinsic activity compared to other full mu-opioid agonists such asheroin,oxycodone, ormethadone.This means that buprenorphine preferentially binds the opioid receptor and displaces lower affinity opioids without activating the receptor to a comparable degree. Clinically, this results in a slow onset of action and a clinical phenomenon known as the ""ceiling effect"" where once a certain dose is reached buprenorphine's effects plateau. This effect can be beneficial, however, as dose-related side effects such as respiratory depression, sedation, and intoxication also plateau at around mg, resulting in a lower risk of overdose compared tomethadoneand other full agonist opioids.,It also means that opioid-dependent patients do not experience sedation or euphoria at the same rate that they might experience with more potent opioids, improving quality of life for patients with severe pain and reducing the reinforcing effects of opioids which can lead to drug-seeking behaviours.Buprenorphine's high affinity, but low intrinsic activity for the mu-opioid receptor also means that if it is started in opioid-dependent individuals, it will displace the other opioids without creating an equal opioid effect and cause a phenomenon known as ""precipitated withdrawal"" which is characterized by a rapid and intense onset of withdrawal symptoms (i.e. anxiety, restlessness, gastrointestinal distress, diaphoresis, intense drug cravings, and tachycardia). Individuals must therefore be in a state of mild to moderate withdrawal before starting therapy with buprenorphine.Buprenorphine is commercially available as the brand name product Suboxone which is formulated in a : fixed-dose combination product along withnaloxone, a non-selective competitive opioid receptor antagonist. Combination of an opioid agonist with an opioid antagonist may seem counterintuitive, however this combination with naloxone is intended to reduce the abuse potential of Suboxone, as naloxone is poorly absorbed by the oral route (and has no effect when taken orally), but would reverse the opioid agonist effects of buprenorphine if injected intravenously.,TargetActionsOrganismAKappa-type opioid receptorantagonistHumansAMu-type opioid receptorpartial agonistHumansUDelta-type opioid receptorantagonistHumansUNociceptin receptorNot AvailableHumans",[],"['Alkaloids', 'Analgesics', 'BCRP/ABCG2 Inhibitors', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Addictive Disorders', 'Drugs Used in Opioid Dependence', 'Heterocyclic Compounds, Fused-Ring', 'Mixed Agonist / Antagonist Opioids', 'Morphinans', 'Narcotics', 'Nervous System', 'Opiate Agonists', 'Opiate Alkaloids', 'Opiate Partial Agonists', 'Opioid Antagonists', 'Opioids', 'Oripavine Derivatives', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'UGT1A1 Substrates', 'UGT1A9 Substrates']" +DB01212,Ceftriaxone,"Ceftriaxoneis a broad-spectrum cephalosporin antibiotic used for the treatment of bacterial infections in various locations, such as in the respiratory tract, skin, soft tissue, and urinary tract.","['P0A3M6', 'Q9NSA0', 'Q4U2R8', 'Q8TCC7', 'P46059']","Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms.11Ceftriaxone hasin vitroactivity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria.12The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs).10Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases.11However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability.10Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate.11Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.11,2",[H][C@]12SCC(CSC3=NC(=O)C(=O)NN3C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O,"Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall.,The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death.TargetActionsOrganismAPenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)USolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumans",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta Lactam Antibiotics', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'P-glycoprotein inhibitors', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB01076,Atorvastatin,Atorvastatinis an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke.,"['P04035', 'P27487', 'P35869', 'Q92769', 'Q14994']","Atorvastatin is an oral antilipemic agent that reversibly inhibits HMG-CoA reductase. It lowers total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), non-high density lipoprotein-cholesterol (non-HDL-C), and triglyceride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease, and high ratios are associated with a higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, atorvastatin reduces the risk of cardiovascular morbidity and mortality.21,9,10,27Elevated cholesterol levels (and high low-density lipoprotein (LDL) levels in particular) are an important risk factor for the development of CVD.9Clinical studies have shown that atorvastatin reduces LDL-C and total cholesterol by 36-53%.3In patients with dysbetalipoproteinemia, atorvastatin reduced the levels of intermediate-density lipoprotein cholesterol.2It has also been suggested that atorvastatin can limit the extent of angiogenesis, which can be useful in the treatment of chronic subdural hematoma.1Myopathy/RhabdomyolysisAtorvastatin, like other HMG-CoA reductase inhibitors, is associated with a risk of drug-induced myopathy characterized by muscle pain, tenderness, or weakness in conjunction with elevated levels of creatine kinase (CK). Myopathy often manifests as rhabdomyolysis with or without acute renal failure secondary to myoglobinuria. The risk of statin-induced myopathy is dose-related, and the symptoms of myopathy are typically resolved upon drug discontinuation. Results from observational studies suggest that 10-15% of people taking statins may experience muscle aches at some point during treatment.30Liver DysfunctionStatins, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevations (> 3 times the upper limit of normal [ULN] occurring on two or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. This effect appears to be dose-related.41,42Endocrine EffectsStatins are associated with a risk of increased serum HbA1c and glucose levels. Anin vitrostudy demonstrated a dose-dependent cytotoxic effect on human pancreatic islet β cells following treatment with atorvastatin. Moreover, insulin secretion rates decreased relative to control.7HMG-CoA reductase inhibitors interfere with cholesterol synthesis and may theoretically interfere with the production of adrenal and/or gonadal steroids. Clinical studies with atorvastatin and other HMG-CoA reductase inhibitors have suggested that these agents do not affect plasma cortisol concentrations, basal plasma testosterone concentration, or adrenal reserve. However, the effect of statins on male fertility has not been fully investigated. The effects of statins on the pituitary-gonadal axis in premenopausal women are unknown.42CardiovascularSignificant decreases in circulating ubiquinone levels in patients treated with atorvastatin and other statins have been observed. The clinical significance of a potential long-term statin-induced deficiency of ubiquinone has not been established. It has been reported that a decrease in myocardial ubiquinone levels could lead to impaired cardiac function in patients with borderline congestive heart failure.42Lipoprotein AIn some patients, the beneficial effect of lowered total cholesterol and LDL-C levels may be partly blunted by the concomitant increase in Lp(a) lipoprotein concentrations. Present knowledge suggests the importance of high Lp(a) levels as an emerging risk factor for coronary heart disease.42Further studies have demonstrated statins affect Lp(a) levels differently in patients with dyslipidemia depending on their apo(a) phenotype; statins increase Lp(a) levels exclusively in patients with the low molecular weight apo(a) phenotype.28",CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CC[C@@H](O)C[C@@H](O)CC(O)=O)C1=CC=C(F)C=C1)C1=CC=CC=C1,"Atorvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (-hydroxy--methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis.,Atorvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low-density lipoprotein (LDL) receptors, which increases hepatic uptake of LDL. Atorvastatin also reduces Very-Low-Density Lipoprotein-Cholesterol (VLDL-C), serum triglycerides (TG) and Intermediate Density Lipoproteins (IDL), as well as the number of apolipoprotein B (apo B) containing particles, but increases High-Density Lipoprotein Cholesterol (HDL-C).In vitroandin vivoanimal studies also demonstrate that atorvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.These effects include improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response. Statins were also found to bind allosterically to β integrin function-associated antigen- (LFA-), which plays an essential role in leukocyte trafficking and T cell activation.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUDipeptidyl peptidase inhibitorHumansUAryl hydrocarbon receptoragonistHumansUHistone deacetylase inhibitorHumansUNuclear receptor subfamily group I member ligandHumans",[],"['Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Fatty Acids', 'Heptanoic Acids', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Lipids', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'OATP2B1/SLCO2B1 substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Toxic Actions', 'UGT1A1 Substrates', 'UGT1A3 substrates']" +DB09270,Ubidecarenone,Ubidecarenoneis a cofactor found in various dietary supplements.,"['P56181', 'P31040']","Ubidecarenon has roles in many prysiological process including sulfide oxidation, regulation of mitochondrial permeability transition pore and translocation of protons and calcium ions accross biological membranes. Studies have shown its benefitial effect in treating cancer, statin myopathy, congestive heart failure and hypertension.2",COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O,"Ubidecarenone is an essential cofactor in the mitochondrial electron transport chain. Its functions are the acceptance of electrons from the complex I and II and this activity is vital for the production of ATP. It acts as a mobile redox agent shuttling electrons and protons in the electron transport chain.Ubidecarenone also presents antioxidant activity in mitochondria and cellular membranes, protecting against peroxidation of lipid membranes as well as inhibiting oxidation of LDL-cholesterol.TargetActionsOrganismANADH dehydrogenase [ubiquinone] flavoprotein , mitochondrialcofactorHumansASuccinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialcofactorHumans",[],"['Agents Causing Muscle Toxicity', 'Benzoquinones', 'Cardiac Therapy', 'Coenzymes', 'Diet, Food, and Nutrition', 'Electron Transport Chain Complex Proteins', 'Enzymes and Coenzymes', 'Food', 'Hypoglycemia-Associated Agents', 'Micronutrients', 'Other Nutritional Agents', 'P-glycoprotein substrates', 'Physiological Phenomena', 'Quinones', 'Ubiquinone', 'Vitamins']" +DB08882,Linagliptin,Linagliptinis a dipeptidyl peptidase-4 (DPP-4) inhibitor used to manage hyperglycemia in patients with type 2 diabetes mellitus.,['P27487'],"A 5mg oral dose of linagliptin results in >80% inhibition of dipeptidyl peptidase 4 (DPP-4) for ≥24 hours3. Inhibition of DPP-4 increases the concentration of glucagon-like peptide 1 (GLP-1), leading to decreased glycosylated hemoglobin and fasting plasma glucose3.",CC#CCN1C(=NC2=C1C(=O)N(CC1=NC3=C(C=CC=C3)C(C)=N1)C(=O)N2C)N1CCC[C@@H](N)C1,"Linagliptin is a competitive, reversible DPP- inhibitor. Inhibition of this enzyme slows the breakdown of GLP- and glucose-dependant insulinotropic polypeptide (GIP),. GLP- and GIP stimulate the release of insulin from beta cells in the pancreas while inhibiting release of glucagon from pancreatic beta cells. These effects together reduce the breakdown of glycogen in the liver and increase insulin release in response to glucose.TargetActionsOrganismADipeptidyl peptidase inhibitorHumans",[],"['Agents causing angioedema', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'DPP-IV Inhibitors', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Incretins', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Oral Hypoglycemics', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Purines', 'Quinazolines']" +DB11672,Curcumin,"Curcumin, also known as diferuloylmethane, is an active component in the golden spice turmeric (Curcuma longa) and inCurcuma xanthorrhiza oil. It is a highly pleiotropic molecule that exhibits antibacterial, anti-inflammatory, hypoglycemic, antioxidant, wound-healing, and antimicrobial activities1. Due to these properties, curcumin has been investigated for the treatment and supportive care of clinical conditions including proteinuria, breast cancer, multiple myeloma, depression, and Non Small Cell Lung Cancer (NSCLC). Despite proven efficacy against numerous experimental models, poor bioavailability due to poor absorption, rapid metabolism, and rapid systemic elimination have been shown to limit the therapeutic efficacy of curcumin1. Curcumin is under investigation for the treatment and supportive care of various clinical conditions including mucositis, rectal cancer, prostate cancer, chronic schizophrenia, and Mild Cognitive Impairment (MCI)1.","['P37231', 'P11473', 'O15440', 'P16152', 'P09211']","Intravenous application of 25 mg/kg bw curcumin to rats resulted in an increase in bile flow by 80 and 120%3. In the rat model of inflammation, curcumin was shown to inhibit edema formation. In nude mouse that had been injected subcutaneously with prostate cancer cells, administration of curcumin caused a marked decrease in the extent of cell proliferation, a significant increase of apoptosis and micro-vessel density3. Curcumin may exert choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility3. Curcumin inhibited arachidonic acid-induced platelet aggregationin vitro3.",COC1=CC(\C=C\C(=O)CC(=O)\C=C\C2=CC(OC)=C(O)C=C2)=CC=C1O,"Curcumin acts as a scavenger of oxygen species, such as hydroxyl radical, superoxide anion, and singlet oxygen and inhibit lipid peroxidation as well as peroxide-induced DNA damage. Curcumin mediates potent anti-inflammatory agent and anti-carcinogenic actions via modulating various signalling molecules. It suppresses a number of key elements in cellular signal transduction pathways pertinent to growth, differentiation, and malignant transformation; it was demonstratedin vitrothat curcumin inhibits protein kinases, c-Jun/AP- activation, prostaglandin biosynthesis, and the activity and expression of the enzyme cyclooxygenase (COX)-.TargetActionsOrganismUPeroxisome proliferator-activated receptor gammaNot AvailableHumansUVitamin D receptorNot AvailableHumansUMultidrug resistance-associated protein inhibitorHumansUCarbonyl reductase [NADPH] Not AvailableHumansUGlutathione S-transferase PNot AvailableHumans",[],"['Alkanes', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Antineoplastic Agents', 'Antirheumatic Agents', 'Benzene Derivatives', 'Catechols', 'Coloring Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Diarylheptanoids', 'Enzyme Inhibitors', 'Heptanes', 'Hydrocarbons, Acyclic', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenols', 'Sensory System Agents']" +DB01064,Isoprenaline,Isoprenalineis a catecholamine non-selective beta-adrenergic agonist typically used to treat bradycardia and heart block.,"['P08588', 'P07550', 'P13945', 'P00441']","Isoprenaline is a non-selective beta adrenergic receptor agonist used in a number of indications for the heart, as well as bronchospasm in anesthesia.2,14Isoprenaline has a short duration of action as it is rapidly cleared,8,7and a wide therapeutic index.14Patients should be counselled regarding the risks of isoprenaline in the treatment of cardiogenic shock following myocardial infarction, paradoxical worsening of heart block, or precipitation of Adams-Stokes attacks.14",CC(C)NCC(O)C1=CC(O)=C(O)C=C1,"Isoprenaline is a non-selective beta adrenergic receptor agonist.Agonism of beta- and beta- adrenergic receptors causes the alpha subunit of G-protein coupled receptors to exchange GMP for GTP, activating them, and allowing the alpha subunit to dissociate from the beta and gamma subunits.,Dissociation of the alpha subunit activates adenylate cyclase, converting ATP to cyclic AMP.Cyclic AMP activates protein kinase A (PKA), which phosphorylates cardiac L-type calcium channels such as Cav..,,These channels depolarize cells by inward active transport of calcium ions.,Agonism of beta- adrenergic receptors lead to increased strength of contractility, conduction of nerve impulses, speed of relaxation, and rate in the heart.Agonism of beta- adrenergic receptors leads to glycogenolysis in the liver,glucagon release from the pancreas, and activation of the renin-angiotensin-aldosterone system.In the alveoli, agonism of beta- adrenergic receptors, activates similar pathways to the heart, however the end result is regulation of sodium channels, the cystic fibrosis transmembrane conductance regulator (CFTR), and sodium potassium ATPase.PKA phosphorylates scaffolding proteins and sodium channels, increasing the number of sodium channels on the apical side of alveolar cells and increasing active transport of sodium ions into cells.Agonism of beta- adrenergic receptors can also increase chloride ion transport across CFTR.Together, these actions lead to passive transport of water out of the alveoli, and the clearance of alveolar fluid.TargetActionsOrganismABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistbinderHumansABeta- adrenergic receptoragonistHumansUSuperoxide dismutase [Cu-Zn]stabilizationHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic and Dopaminergic Agents', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Benzene Derivatives', 'Bronchodilator Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'Cholinesterase Inhibitors', 'Compounds used in a research, industrial, or household setting', 'COMT Substrates', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Neurotransmitter Agents', 'Non-selective Beta-adrenergic Agonists', 'Peripheral Nervous System Agents', 'Phenols', 'Protective Agents', 'Respiratory System Agents', 'Sympathomimetics']" +DB01112,Cefuroxime,"Cefuroximeis a cephalosporin indicated for the treatment of a variety of infections including acute bacterial otitis media, several upper respiratory tract infections, skin infections, urinary tract infections, gonorrhea, early Lyme disease, and impetigo.",['Q8XJ01'],"Cefuroxime is a β-lactam type antibiotic. More specifically, it is a second-generation cephalosporin. Cephalosporins work the same way as penicillins: they interfere with the peptidoglycan synthesis of the bacterial wall by inhibiting the final transpeptidation needed for the cross-links. This effect is bactericidal. Cefuroxime is effective against the following organisms: Aerobic Gram-positive Microorganisms:Staphylococcus aureus,Streptococcus pneumoniae,Streptococcus pyogenes. Aerobic Gram-negative Microorganisms:Escherichia coli,Haemophilus influenzae(including beta-lactamase-producing strains),Haemophilus parainfluenzae,Klebsiella pneumoniae,Moraxella catarrhalis(including beta-lactamase-producing strains),Neisseria gonorrhoeae(including beta-lactamase-producing strains). Spirochetes:Borrelia burgdorferi. Cefuroxime axetil is the prodrug",[H][C@]12SCC(COC(N)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CC=CO1)C(O)=O,"Cefuroxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefuroxime interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Ophthalmologicals', 'Second-Generation Cephalosporins', 'Sensory Organs', 'Sulfur Compounds', 'Thiazines']" +DB00166,Lipoic acid,A vitamin-like antioxidant.,"['Q9Y234', 'Q9Y289', 'O43766']","Lipoic acid (or α-lipoic acid) is able to pass the blood-brain barrier and is putatively used for detoxification of mercury attached to the brain cells. It can mobilise bound mercury into the blood stream as it is a mercaptan (sulfur compound which readily binds to the mercury). In the blood stream, another chelator such as dimercaptosuccinic acid (DMSA) or methylsulfonylmethane (MSM) is used to transfer mercury safely into the urine for excretion. Neither DMSA nor MSM can cross the blood-brain barrier, which is why both lipoic acid and DMSA are used. It is hypothesized that this treatment-along with carnitine, dimethylglycine (DMG), Vitamin B6, folic acid, and magnesium—could be used to treat autism and amalgam poisoning. In this hypothesis, the reason why autism is difficult to treat is that mercury is attached to the brain cells and most medicines and vitamin supplements do not penetrate the blood-brain barrier. However, α-lipoic acid and perhaps vitamin B12 could making it possible for other chelators to remove mercury safely out of the body and could perhaps one day be used as a treatment for autism. Because lipoic acid is related to cellular uptake of glucose and it is both soluble in water and fat, it is being used for treatment in diabetes. It may be helpful for people with Alzheimer's disease or Parkinson's disease.",OC(=O)CCCC[C@@H]1CCSS1,"Lipoic Acid is generally involved in oxidative decarboxylations of keto acids and is presented as a growth factor for some organisms. Lipoic acid exists as two enantiomers, the R-enantiomer and the S-enantiomer. Normally only the R-enantiomer of an amino acid is biologically active, but for lipoic acid the S-enantiomer assists in the reduction of the R-enantiomer when a racemic mixture is given. Some recent studies have suggested that the S-enantiomer in fact has an inhibiting effect on the R-enantiomer, reducing its biological activity substantially and actually adding to oxidative stress rather than reducing it. Furthermore, the S-enantiomer has been found to reduce the expression of GLUT-s in cells, responsible for glucose uptake, and hence reduce insulin sensitivity.TargetActionsOrganismULipoyltransferase , mitochondrialNot AvailableHumansUSodium-dependent multivitamin transporterNot AvailableHumansULipoyl synthase, mitochondrialNot AvailableHumans","['Dietary and Nutritional Therapies', 'Nutritional supplementation']","['Alimentary Tract and Metabolism', 'Antioxidants', 'Biological Factors', 'Coenzymes', 'Compounds used in a research, industrial, or household setting', 'Dietary Supplements', 'Enzymes and Coenzymes', 'Fatty Acids', 'Hypoglycemia-Associated Agents', 'Lipids', 'Micronutrients', 'Protective Agents', 'Sulfur Compounds', 'Supplements', 'Thiophenes', 'Various Alimentary Tract and Metabolism Products', 'Vitamin B Complex', 'Vitamins']" +DB00435,Nitric Oxide,Nitric Oxideis a vasodilating agent used in the treatment of hypoxic respiratory failure in premature neonates.,"['P33402', 'P04731', 'P14902', 'P29474']","Persistent pulmonary hypertension of the newborn (PPHN) occurs as a primary developmental defect or as a condition secondary to other diseases such as meconium aspiration syndrome (MAS), pneumonia, sepsis, hyaline membrane disease, congenital diaphragmatic hernia (CDH), and pulmonary hypoplasia. In these states, pulmonary vascular resistance (PVR) is high, which results in hypoxemia secondary to right-to-left shunting of blood through the patent ductus arteriosus and foramen ovale. In neonates with PPHN, Nitric oxide improves oxygenation (as indicated by significant increases in PaO2). Nitric oxide appears to increase the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better entilated areas of the lung, redistributing pulmonary blood flow away from lung regions with low ventilation/perfusion (V/Q) ratios toward regions with normal ratios.",[N]=O,"Nitric oxide is a compound produced by many cells of the body. It relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine ','-monophosphate, which then leads to vasodilation. When inhaled, nitric oxide produces pulmonary vasodilation.TargetActionsOrganismAGuanylate cyclase soluble subunit alpha-inducerHumansUMetallothionein-ANot AvailableHumansUIndoleamine ,-dioxygenase Not AvailableHumansUNitric oxide synthase, endothelialproduct ofHumans",[],"['Anti-Asthmatic Agents', 'Antioxidants', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Endothelium-Dependent Relaxing Factors', 'Free Radical Scavengers', 'Free Radicals', 'Gases', 'Gasotransmitters', 'Hypotensive Agents', 'Methemoglobinemia Associated Agents', 'Neurotransmitter Agents', 'Nitrates and Nitrites', 'Nitrogen Compounds', 'Nitrogen Oxides', 'Oxides', 'Oxygen Compounds', 'Peripheral Nervous System Agents', 'Reactive Nitrogen Species', 'Respiratory System Agents', 'Vasodilating Agents', 'Vasodilation']" +DB00960,Pindolol,"Pindololis a beta adrenoceptor antagonist used to treat hypertension, edema, ventricular tachycardias, and atrial fibrillation.","['P08588', 'P07550', 'P13945', 'P08908', 'P28222']","Pindolol is a nonselective beta blocker indicated in the management of hypertension9and prophylaxis of angina.10It has a short duration of action as it is given twice daily, and a wide therapeutic window as doses can range from 10-60 mg/day.9Patients should be counselled regarding the risk of cardiac failure, exacerbating ischemic heart disease with sudden withdrawal, nonallergic bronchospasm, masking hypoglycemia in diabetics, and masking hyperthyroidism.9",CC(C)NCC(O)COC1=CC=CC2=C1C=CN2,"The beta- adrenoceptor is a G-protein-coupled receptor.Agonism of the beta- adrenoceptor allows the Gs subunit to upregulate adenylyl cyclase, converting ATP to cyclic AMP (cAMP).Increased concentrations of cAMP activate cAMP-dependant kinase A, phosphorylating calcium channels, raising intracellular calcium, increasing calcium exchange through the sarcoplasmic reticulum, and increasing cardiac inotropy.cAMP-dependant kinase A also phosphorylates myosin light chains, increasing smooth muscle contractility.Increased smooth muscle contractility in the kidney releases renin.Pindolol is a non-selective beta blocker.Blocking beta- adrenergic receptors in the heart results in decreased heart rate and blood pressure.By blocking beta- receptors in the juxtaglomerular apparatus, pindolol inhibits the release of renin, which inhibits angiotensin II and aldosterone release.,Reduced angiotensin II inhibits vasoconstriction and reduced aldosterone inhibits water retention.,Beta- adrenoceptors located in the kidneys and peripheral blood vessels use a similar mechanism to activate cAMP-dependant kinase A to increase smooth muscle contractility.Blocking of the beta- adrenoceptor relaxes smooth muscle, leading to vasodilation.TargetActionsOrganismABeta- adrenergic receptorpartial agonistHumansABeta- adrenergic receptorpartial agonistHumansUBeta- adrenergic receptoragonistHumansU-hydroxytryptamine receptor AantagonistinhibitorligandHumansU-hydroxytryptamine receptor Bother/unknownligandHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antidepressive Agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Beta Blocking Agents, Non-Selective', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Neurotransmitter Agents', 'OCT2 Substrates', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Vasodilating Agents']" +DB00746,Deferoxamine,Deferoxamineis a chelating agent used to treat iron or aluminum toxicity and some blood transfusion dependent anemias.,['P05067'],"Deferoxamine, otherwise known as desferrioxamine or desferal, is a chelating agent used to remove excess iron or aluminum from the body. It acts by binding free iron or aluminum in the bloodstream and enhancing its elimination in the urine. By removing excess iron or aluminum, the agent reduces the damage done to various organs and tissues, such as the liver.",CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN,"Deferoxamine works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming ferrioxamine, a stable complex which is eliminated via the kidneys. mg of deferoxamine is capable of binding approximately . mg of trivalent (ferric) iron. Deferoxamine works in treating aluminum toxicity by binding to tissue-bound aluminum to form aluminoxamine, a stable, water-soluble complex. The formation of aluminoxamine increases blood concentrations of aluminum, resulting in an increased concentration gradient between the blood and dialysate, boosting the removal of aluminum during dialysis. mg of deferoxamine is capable of binding approximately . mg of aluminum.TargetActionsOrganismAIronchelatorHumansAAluminumchelatorHumansUAmyloid beta A proteinNot AvailableHumans",[],"['Amines', 'Chelating Agents', 'Compounds used in a research, industrial, or household setting', 'Heavy Metal Antagonists', 'Hydroxamic Acids', 'Hydroxy Acids', 'Hydroxylamines', 'Iron Chelating Activity', 'Iron Chelating Agents', 'Sequestering Agents', 'Siderophores']" +DB06782,Dimercaprol,"Dimercaprolis a chelating agent used as an antidote to arsenic, gold, and mercury poisoning, as well as acute lead poisoning in combination with edetate calcium disodium.",['P05067'],"Due to its oily nature, dimercaprol is not absorbed orally and its administration requires a deep intra-muscular injection that is extremely painful and allergenic. It was found to mobilize and relocate lead to the brain, increasing its neurotoxic effects. Despite that fact that dimercaprol increases cadmium excretion, there is an associated increase in kidney cadmium concentration. Because of this, dimercaprol must be avoided in patients with cadmium toxicity.",OCC(S)CS,The sulfhydryl groups of dimercaprol form complexes with certain heavy metals thus preventing or reversing the metallic binding of sulfhydryl-containing enzymes. The complex is excreted in the urine.TargetActionsOrganismAArsenicchelatorHumansACadmiumchelatorHumansAMercurychelatorHumansUAmyloid beta A proteinNot AvailableHumans,[],"['Antidotes', 'Chelating Agents', 'Compounds used in a research, industrial, or household setting', 'Drugs that are Mainly Renally Excreted', 'Heavy Metal Antagonists', 'Metal Chelating Activity', 'Metal Chelator', 'Sequestering Agents', 'Sulfhydryl Compounds', 'Sulfur Compounds']" +DB05294,Vandetanib,Vandetanibis an antineoplastic kinase inhibitor used to treat symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.,"['P15692', 'P00533', 'Q13882', 'Q02763', 'P07949']",Mean IC50 of approximately 2.1 μg/mL.,COC1=C(OCC2CCN(C)CC2)C=C2N=CN=C(NC3=C(F)C=C(Br)C=C3)C2=C1,"ZD- is a potent and selective inhibitor of VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor) and RET (REarranged during Transfection) tyrosine kinases.VEGFR- and EGFR-dependent signalling are both clinically validated pathways in cancer, including non-small-cell lung cancer (NSCLC). RET activity is important in some types of thyroid cancer, and early data with vandetanib in medullary thyroid cancer has led to orphan-drug designation by the regulatory authorities in the USA and EU.TargetActionsOrganismUVascular endothelial growth factor AinhibitorHumansUEpidermal growth factor receptorinhibitorHumansUProtein-tyrosine kinase inhibitorHumansUAngiopoietin- receptorinhibitorHumansUProto-oncogene tyrosine-protein kinase receptor RetNot AvailableHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Tyrosine Kinase Inhibitors']" +DB00571,Propranolol,"Propranololis a non-selective beta adrenergic antagonist used to treat hypertension, angina, atrial fibrillation, myocardial infarction, migraine, essential tremor, hypertrophic subaortic stenosis, and pheochromocytoma.","['P08588', 'P07550', 'P13945', 'P08908', 'P28222']","Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension.9,10Propranolol has a long duration of action as it is given once or twice daily depending on the indication.8,9,10When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.10",CC(C)NCC(O)COC1=CC=CC2=C1C=CC=C2,"Propranolol is a nonselective β-adrenergic receptor antagonist.Blocking of these receptors leads to vasoconstriction, inhibition of angiogenic factors like vascular endothelial growth factor (VEGF) and basic growth factor of fibroblasts (bFGF), induction of apoptosis of endothelial cells, as well as down regulation of the renin-angiotensin-aldosterone system.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumansU-hydroxytryptamine receptor Aother/unknownHumansU-hydroxytryptamine receptor Bother/unknownHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Non-Selective', 'Beta Blocking Agents, Non-Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Naphthalenes', 'Negative Inotrope', 'Neurotransmitter Agents', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB00361,Vinorelbine,Vinorelbineis a vinca alkaloid used in the treatment of metastatic non-small cell lung carcinoma (NSLC) and in conjunction with other drugs in locally advanced NSCLC.,['P07437'],"Vinorelbine is a semi-synthetic vinca-alkaloid with a wide spectrum of anti-tumor activity. The vinca-alkaloids are considered spindle poisons. They work by interfering with the polymerization of tubulin, a protein responsible for building the microtubule system which appears during cell division in proliferating cancer cells11.",[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC,"Vinca alkaloids are structurally similar compounds composed of two multi-ringed units,vindoline, andcatharanthine.Vinorelbine tartrateis a vinca alkaloid in which the catharanthine component is the target of structural modification,.This structural modification contributes to unique pharmacologic properties.The antitumor activity of vinorelbine tartrate is believed to be owed to the inhibition of mitosis at metaphase via its interaction with tubulin.Vinorelbine is a mitotic spindle poison that interferes with chromosomal segregation during mitosis, also known as cell division. It pauses cells at theG/Mphases, when present at concentrations close to the half maximal inhibitory concentration (IC). Microtubules, which are derived from polymers of tubulin, are the main target of vinorelbine.The chemical modification used to produce vinorelbine allows for the opening of the eight-member catharanthine ring with the formation of both a covalent and reversible bond with tubulin.The relative contribution of different microtubule-associated proteins in the production of tubulin vary between neural tissue and proliferating cells and this has important functional implications. The ability of vinorelbine to bind specifically to mitotic rather than other microtubules has been shown and may suggest that neurotoxicity is less likely to be a problem than with the molecular mechanism of action.As with other anti-microtubule agents, vinorelbine is known to contribute apoptosis in malignant cells. The exact mechanisms by which this process occurs are complex and many details are yet to be elucidated. The disarray of the microtubule structure has a number of effects, including the induction of tumor suppressor genepand activation/inactivation of a number of protein kinases involved in essential signaling pathways, includingp WAF/CIPandRas/Raf,PKC/PKA. These molecular changes lead to phosphorylation and consequently inactivation of the apoptosis inhibitorBcl. This, in turn, results in a decrease in the formation of heterodimers betweenBcland the pro-apoptotic geneBAX, stimulating the sequence of cell apoptosis.Vinorelbine tartrate also possibly interferes with amino acid, cyclic AMP and glutathione metabolism, calmodulin-dependent Ca++-transport ATPase activity, cellular respiration, and nucleic acid and lipid biosynthesis.TargetActionsOrganismATubulin beta chainantagonistinhibitorHumans",[],"['Alkaloids', 'Antimitotic Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Mitosis Modulators', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Neurotoxic agents', 'Secologanin Tryptamine Alkaloids', 'Tubulin Modulators', 'Vinca Alkaloids']" +DB08865,Crizotinib,"Crizotinibis a receptor tyrosine kinase inhibitor used to treat metastatic non-small cell lung cancer (NSCLC) where the tumors have been confirmed to be anaplastic lymphoma kinase (ALK), or ROS1-positive.","['Q9UM73', 'P08581', 'P08922', 'Q04912']","In a phase I study, 37 patients with a variety of solid-tumor cancers refractory to therapy received 50 to 300 mg of crizotinib daily or twice daily. In this group, two patients with non-small cell lung cancer (NSCLC) exhibiting echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) mutations responded to therapy; therefore, following studies focused on patients with advanced ALK-positive disease.1In this group of patients, the 6-month progression-free survival among crizotinib users was approximately 72%. When compared to ALK mutation-positive patients that did not receive crizotinib, ALK mutation-positive patients treated with crizotinib had a higher two-year overall survival rate (54% vs 36%).1The use of crizotinib may lead to hepatotoxicity, interstitial lung disease (ILD), pneumonitis, QT interval prolongation, bradycardia, severe visual loss, ​​embryo-fetal toxicity and gastrointestinal toxicity in pediatric and young adult patients with anaplastic large cell lymphoma (ALCL) or pediatric patients with inflammatory myofibroblastic tumor (IMT).4",C[C@@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl,"Crizotinib is a tyrosine kinase receptor inhibitor that targets anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), ROS (c-ros), and Recepteur d'Origine Nantais (RON).When activated, ALK inhibits apoptosis and promotes cell proliferation, and ALK-gene translocations can lead to the expression of oncogenic fusion proteins. A small portion of non-small cell lung cancer (NSCLC) patients have ALK-positive tumors. Most of these cases are characterized by the fusion of ALK with the chimeric protein echinoderm microtubule-associated protein-like (EML), resulting in increased kinase activity.,Crizotinib inhibits ALK by inhibiting its phosphorylation and creating an inactive protein conformation.This ultimately lowers the proliferation of cells carrying this genetic mutation and tumour survivability.In vitroassays on tumor cell lines demonstrated that crizotinib inhibits ALK, ROS, and c-Met phosphorylation in a concentration-dependent manner.In vivostudies in mice with tumor xenografts that expressed EML- or nucleophosmin (NPM)-ALK fusion proteins or c-Met showed that crizotinib has antitumor activity.TargetActionsOrganismAALK tyrosine kinase receptorinhibitorHumansAHepatocyte growth factor receptorinhibitorHumansAProto-oncogene tyrosine-protein kinase ROSinhibitorHumansAMacrophage-stimulating protein receptorinhibitorHumans",[],"['Aminopyridines', 'Anaplastic lymphoma kinase (ALK) inhibitors', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Kinase Inhibitor', 'Moderate Risk QTc-Prolonging Agents', 'Narrow Therapeutic Index Drugs', 'OCT2 Inhibitors', 'Organic Cation Transporter 1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Piperidines', 'Protein Kinase Inhibitors', 'Pyridines', 'QTc Prolonging Agents', 'Receptor Tyrosine Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB00317,Gefitinib,Gefitinibis a tyrosine kinase inhibitor used as first-line therapy to treat non-small cell lung carcinoma (NSCLC) that meets certain genetic mutation criteria.,['P00533'],"Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.",COC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C1,"Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to enhanced activation of the anti-apoptotic Ras signal transduction cascades, subsequently resulting in increased survival of cancer cells and uncontrolled cell proliferation. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her or ErbB-. By inhibiting EGFR tyrosine kinase, the downstream signaling cascades are also inhibited, resulting in inhibited malignant cell proliferation.TargetActionsOrganismAEpidermal growth factor receptorantagonistHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Kinase Inhibitor', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protein Kinase Inhibitors', 'Quinazolines', 'Tyrosine Kinase Inhibitors']" +DB00277,Theophylline,"Theophyllineis a xanthine used to manage the symptoms of asthma, COPD, and other lung conditions caused by reversible airflow obstruction.","['P30542', 'P29274', 'P29275', 'Q07343', 'O76074', 'P27815', 'Q14432', 'Q92769', 'Q99829', 'Q8TCT9', 'Q15155', 'P09874', 'Q7Z5B4', 'Q9Y4R7']","Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).",CN1C2=C(NC=N2)C(=O)N(C)C1=O,"Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine AB receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.TargetActionsOrganismAAdenosine receptor AantagonistHumansAAdenosine receptor AaantagonistHumansAAdenosine receptor AbantagonistHumansAcAMP-specific ','-cyclic phosphodiesterase BinhibitorHumansAcGMP-specific ','-cyclic phosphodiesteraseinhibitorHumansAcAMP-specific ','-cyclic phosphodiesterase AinhibitorHumansAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumansAHistone deacetylase activatorHumansUCopine-Not AvailableHumansUMinor histocompatibility antigen HNot AvailableHumansUNodal modulator Not AvailableHumansUPoly [ADP-ribose] polymerase Not AvailableHumansUProtein RIC-Not AvailableHumansUTubulin monoglycylase TTLLNot AvailableHumans","['Airway secretion clearance therapy', 'Bronchodilation']","['Agents that reduce seizure threshold', 'Alkaloids', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P1 Receptor Antagonists', 'Purines', 'Purinones', 'Respiratory Smooth Muscle Relaxants', 'Respiratory System Agents', 'Vasodilating Agents', 'Xanthine derivatives', 'Xanthines and Adrenergics']" +DB00780,Phenelzine,"Phenelzineis a monoamine oxidase inhibitor used to treat atypical, nonendogenous, or neurotic depression.","['P21397', 'P27338', 'Q16853', 'P80404', 'P24298', 'Q8TD30', 'Q9UGI5']","The elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings.7Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia.3",NNCCC1=CC=CC=C1,"The basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Phenelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase.TargetActionsOrganismAAmine oxidase [flavin-containing] AantagonistHumansAAmine oxidase [flavin-containing] BantagonistHumansUMembrane primary amine oxidaseinhibitorHumansU-aminobutyrate aminotransferase, mitochondrialinhibitorHumansUAlanine aminotransferase inhibitorHumansUAlanine aminotransferase inhibitorHumansUGlutamic acid decarboxylaseinhibitorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hydrazines', 'Hypotensive Agents', 'Monoamine Oxidase A Substrates', 'Monoamine Oxidase Inhibitors', 'Monoamine Oxidase Inhibitors, Non-Selective', 'Nervous System', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB00642,Pemetrexed,Pemetrexedis a folate analog used to treat mesothelioma and non-small cell lung cancer.,"['P04818', 'P31939', 'P00374', 'P22102']","Pemetrexed inhibited the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052) and showed synergistic +effects when combined with cisplatin. Based on population pharmacodynamic analyses, the depth of the absolute neutrophil counts (ANC) nadir correlates with systemic exposure to pemetrexed and supplementation with folic acid and vitamin B12. There is no cumulative effect of pemetrexed exposure on ANC nadir over multiple treatment cycles.11",NC1=NC(=O)C2=C(NC=C2CCC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N1,"Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.,,,,,TargetActionsOrganismAThymidylate synthaseinhibitorHumansABifunctional purine biosynthesis protein PURHinhibitorHumansADihydrofolate reductaseinhibitorHumansATrifunctional purine biosynthetic protein adenosine-inhibitorHumans",['Monotherapy'],"['Amino Acids', 'Amino Acids, Acidic', 'Amino Acids, Dicarboxylic', 'Amino Acids, Peptides, and Proteins', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inhibitors', 'Folic Acid Analogues', 'Folic Acid Antagonists', 'Glutamates', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nucleic Acid Synthesis Inhibitors', 'OAT3/SLC22A8 Substrates', 'OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index']" +DB01248,Docetaxel,"Docetaxelis a taxoid antineoplastic agent used in the treatment of various cancers, such as locally advanced or metastatic breast cancer, metastatic prostate cancer, gastric adenocarcinoma, and head and neck cancer.","['Q9H4B7', 'P11137', 'P27816', 'P10636', 'P10415', 'O75469']","Docetaxel is a taxoid antineoplastic agent. It promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network which is essential for vital interphase and mitotic cellular functions. In addition, docetaxel induces abnormal arrays or ""bundles"" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.4,5The use of docetaxel may lead to treatment-related deaths in breast cancer and non-small cell lung cancer patients, hepatic impairment, hematologic effects, enterocolitis and neutropenic colitis, hypersensitivity reactions, fluid retention, second primary malignancies, cutaneous reactions, neurologic reactions, eye disorders, asthenia, embryo-fetal toxicity, and tumor lysis syndrome.7",[H][C@@]1(C[C@@]2(O)[C@@H](OC(=O)C3=CC=CC=C3)[C@]3([H])[C@@]4(CO[C@@H]4C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C(=C1C)C2(C)C)OC(C)=O)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1,"Docetaxel interferes with the normal function of microtubule growth. Whereas drugs likecolchicinecause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the β-subunit of tubulin. Tubulin is the ""building block"" of microtubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis-stopping protein called Bcl- (B-cell leukemia ), thus arresting its function.,,TargetActionsOrganismATubulin beta- chainNot AvailableHumansAMicrotubule-associated protein Not AvailableHumansAMicrotubule-associated protein Not AvailableHumansAMicrotubule-associated protein tauNot AvailableHumansUApoptosis regulator Bcl-Not AvailableHumansUNuclear receptor subfamily group I member binderHumans",[],"['Agents Causing Muscle Toxicity', 'Antimitotic Agents', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cardiotoxic antineoplastic agents', 'Cyclodecanes', 'Cycloparaffins', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diterpenes', 'Hepatotoxic Agents', 'Immunosuppressive Agents', 'Microtubule Inhibition', 'Microtubule Inhibitors', 'Mitosis Modulators', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B3 substrates', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Taxane Derivatives', 'Taxoids', 'Terpenes', 'Tubulin Modulators']" +DB00283,Clemastine,Clemastineis an antihistamine with sedative and anticholinergic effects used to treat the symptoms of allergic rhinitis.,['P35367'],"Clemastine is an antihistamine that also induces anticholinergic and sedative effects. Antihistamines competitively antagonize various physiological effects of histamine including increased capillary permeability and dilatation, the formation of edema, the ""flare"" and ""itch"" response, and gastrointestinal and respiratory smooth muscle constriction. Within the vascular tree, H1- receptor antagonists inhibit both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, H1- receptor antagonists can produce CNS stimulation or depression. Most antihistamines exhibit central and/or peripheral anticholinergic activity. Antihistamines act by competitively blocking H1- receptor sites. Antihistamines do not pharmacologically antagonize or chemically inactivate histamine, nor do they prevent the release of histamine.",CN1CCC[C@@H]1CCO[C@](C)(C1=CC=CC=C1)C1=CC=C(Cl)C=C1,"Clemastine is a selective histamine H antagonist and binds to the histamine H receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Aminoalkyl Ethers', 'Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Antihistamines for Topical Use', 'Antipruritics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Highest Risk QTc-Prolonging Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Pyrrolidines', 'QTc Prolonging Agents']" +DB01098,Rosuvastatin,Rosuvastatinis an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke.,"['P04035', 'P20701']","Rosuvastatin is a synthetic, enantiomerically pure antilipemic agent. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.15,21Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.15Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.16,17,18,26,31Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.15,21Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.19,20Skeletal Muscle EffectsCases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including rosuvastatin. These risks can occur at any dose level, but are increased at the highest dose (40 mg). Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy (e.g., age ≥ 65 years, inadequately treated hypothyroidism, renal impairment).The risk of myopathy during treatment with rosuvastatin may be increased with concurrent administration of some other lipid-lowering therapies (such asfenofibrateorniacin),gemfibrozil,cyclosporine,atazanavir/ritonavir,lopinavir/ritonavir, orsimeprevir. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, coadministered withcolchicine, and caution should therefore be exercised when prescribing these two medications together.46Real-world data from observational studies has suggested that 10-15% of people taking statins may experience muscle aches at some point during treatment.41Liver Enzyme AbnormalitiesIncreases in serum transaminases have been reported with HMG-CoA reductase inhibitors, including rosuvastatin. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. There were two cases of jaundice, for which a relationship to rosuvastatin therapy could not be determined, which resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver disease in these trials.46Endocrine EffectsIncreases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including rosuvastatin calcium tablets. Based on clinical trial data with rosuvastatin, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus.46An in vitro study found thatatorvastatin,pravastatin,rosuvastatin, andpitavastatinexhibited a dose-dependent cytotoxic effect on human pancreas islet β cells, with reductions in cell viability of 32, 41, 34 and 29%, respectively, versus control]. Moreover, insulin secretion rates were decreased by 34, 30, 27 and 19%, respectively, relative to control.40HMG-CoA reductase inhibitors interfere with cholesterol synthesis and lower cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Rosuvastatin demonstrated no effect upon nonstimulated cortisol levels and no effect on thyroid metabolism as assessed by TSH plasma concentration. In rosuvastatin treated patients, there was no impairment of adrenocortical reserve and no reduction in plasma cortisol concentrations. Clinical studies with other HMG-CoA reductase inhibitors have suggested that these agents do not reduce plasma testosterone concentration. The effects of HMG-CoA reductase inhibitors on male fertility have not been studied. The effects, if any, on the pituitarygonadal axis in premenopausal women are unknown.47CardiovascularUbiquinone levels were not measured in rosuvastatin clinical trials, however significant decreases in circulating ubiquinone levels in patients treated with other statins have been observed. The clinical significance of a potential long-term statin-induced deficiency of ubiquinone has not been established. It has been reported that a decrease in myocardial ubiquinone levels could lead to impaired cardiac function in patients with borderline congestive heart failure.47Lipoprotein AIn some patients, the beneficial effect of lowered total cholesterol and LDL-C levels may be partly blunted by a concomitant increase in the Lipoprotein(a) [Lp(a)] concentrations. Present knowledge suggests the importance of high Lp(a) levels as an emerging risk factor for coronary heart disease. It is thus desirable to maintain and reinforce lifestyle changes in high-risk patients placed on rosuvastatin therapy.47Further studies have demonstrated statins affect Lp(a) levels differently in patients with dyslipidemia depending on their apo(a) phenotype; statins increase Lp(a) levels exclusively in patients with the low molecular weight apo(a) phenotype.23",CC(C)C1=NC(=NC(C2=CC=C(F)C=C2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(=O)O)N(C)S(C)(=O)=O,"Rosuvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (-hydroxy--methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis.Rosuvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL).The overall effect is a decrease in plasma LDL and VLDL.In vitro and in vivo animal studies also demonstrate that rosuvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.Statins have also been found to bind allosterically to β integrin function-associated antigen- (LFA-), which plays an important role in leukocyte trafficking and in T cell activation.Rosuvastatin exerts an anti-inflammatory effect on rat mesenteric microvascular endothelium by attenuating leukocyte rolling, adherence and transmigration.The drug also modulates nitric oxide synthase (NOS) expression and reduces ischemic-reperfusion injuries in rat hearts.Rosuvastatin increases the bioavailability of nitric oxide,,by upregulating NOSand by increasing the stability of NOS through post-transcriptional polyadenylation.It is unclear as to how rosuvastatin brings about these effects though they may be due to decreased concentrations of mevalonic acid.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUIntegrin alpha-Linhibitory allosteric modulatorHumans","['Lipid-Lowering Therapy', 'Primary Prevention of Cardiovascular Diseases']","['Agents Causing Muscle Toxicity', 'Alimentary Tract and Metabolism', 'Amides', 'Anticholesteremic Agents', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Fluorobenzenes', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hydrocarbons, Fluorinated', 'Hydrocarbons, Halogenated', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'Pyrimidines', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB00309,Vindesine,"Vindesineis a vinca alkaloid derived from vinblastine used for various types of malignancies, but mainly acute lymphocytic leukemia (ALL).",['Q9H4B7'],"Vindesine is indicated for the treatment of acute lymphocytic leukemia of childhood that is resistant to vincristine and non-oat cell lung cancer. Vindesine causes the arrest of cells in metaphase mitosis. It is three times more potent than vincristine and nearly 10 times more potent than vinblastine in causing mitotic arrest inin vitrostudies at doses designed to arrest from 10 to 15% of the cells in mitosis. Vindesine and vincristine are approximately equipotent at dose levels that arrest 40 to 50% of the cells in mitosis. Unlike vinblastine, vindesine produces very few postmetaphase cells. Vindesine has demonstrated activity in patients who have relapsed while receiving multiple-agent treatment that included vincristine.",[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C)[C@@]1([H])[C@](O)([C@H](O)[C@]2(CC)C=CC3)C(N)=O)[C@]1(C[C@@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=C2C=CC=C1)C(=O)OC,Vindesine acts by causing the arrest of cells in metaphase mitosis through its inhibition tubulin mitotic funcitoning. The drug is cell-cycle specific for the S phase.TargetActionsOrganismATubulin beta- chaininhibitorHumans,[],"['Alkaloids', 'Antimitotic Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Mitosis Modulators', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Secologanin Tryptamine Alkaloids', 'Tubulin Modulators', 'Vinca Alkaloids']" +DB00627,Niacin,Niacinis a B vitamin used to treat hypertriglyceridemia and pellagra.,"['P49019', 'Q8TDS4', 'Q15274', 'P40261']","Niacin is a B vitamin used to treat vitamin deficiencies as well as hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarctions.6,7,8,9,10,11Niacin acts to decrease levels of very low density lipoproteins and low density lipoproteins, while increasing levels of high density lipoproteins.3Niacin has a wide therapeutic window with usual oral doses between 500mg and 2000mg.6Patients with diabetes, renal failure, uncontrolled hypothyroidism, and elderly patients taking niacin with simvastatin or lovastatin are at increased risk of myopathy and rhabdomyolysis.6",OC(=O)C1=CN=CC=C1,"Niacin performs a number of functions in the body and so has many mechanisms, not all of which have been fully described.Niacin can decrease lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver, which degrades apo B, or by modulating lipolysis in adipose tissue.Niacin inhibits hepatocyte diacylglycerol acyltransferase-.This action prevents the final step of triglyceride synthesis in hepatocytes, limiting available triglycerides for very low density lipoproteins (VLDL).This activity also leads to intracellular degradation of apo B and decreased production of low density lipoproteins, the catabolic product of VLDL.Niacin also inhibits a high density lipoprotein (HDL) catabolism receptor, which increases the levels and half life of HDL.TargetActionsOrganismAHydroxycarboxylic acid receptor agonistHumansAHydroxycarboxylic acid receptor agonistHumansANicotinate-nucleotide pyrophosphorylase [carboxylating]binderHumansANicotinamide N-methyltransferasebinderHumans",['Dietary supplementation'],"['Agents Causing Muscle Toxicity', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Diet, Food, and Nutrition', 'Food', 'Growth Substances', 'Hyperglycemia-Associated Agents', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Micronutrients', 'Miscellaneous Antilipemic Agents', 'Nicotinic Acid and Derivatives', 'Nicotinic Acids', 'Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia', 'Noxae', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Peripheral Vasodilators', 'Physiological Phenomena', 'Pyridines', 'Thyroxine-binding globulin inhibitors', 'Toxic Actions', 'Vasodilating Agents', 'Vitamin B Complex', 'Vitamins']" +DB01053,Benzylpenicillin,"Benzylpenicillinis a penicillin used for the treatment of infections caused by gram-positive cocci, in particular streptococcal infections. This form of penicillin is typically used in intravenous or long-acting injectable formulations due to poor oral absorption.","['A0A0H2XJ39', 'Q8TCC7', 'P46059', 'Q16348']","Penicillin G is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name ""penicillin"" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Penicillin G hasin vitroactivity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin G inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that penicillin G interferes with an autolysin inhibitor.TargetActionsOrganismUPenicillin-binding protein inhibitorStaphylococcus aureus (strain USA)USolute carrier family member substrateinhibitorHumansUSolute carrier family member substrateinhibitorHumansUSolute carrier family member inhibitorHumans",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Sensitive Penicillins', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Natural Penicillins', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Substrates', 'OATP2B1/SLCO2B1 substrates', 'Ophthalmologicals', 'Penicillin G', 'Penicillins', 'Sensory Organs', 'Sulfur Compounds']" +DB00224,Indinavir,Indinaviris a protease inhibitor used to treat HIV infection.,['Q72874'],Indinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.,CC(C)(C)NC(=O)[C@@H]1CN(CC2=CN=CC=C2)CCN1C[C@@H](O)C[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]1[C@H](O)CC2=CC=CC=C12,"Indinavir inhibits the HIV viral protease enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Agents Causing Muscle Toxicity', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Pyridines', 'UGT1A1 Inhibitors', 'Viral Protease Inhibitors']" +DB00297,Bupivacaine,Bupivacaineis a local anesthetic used in a wide variety of superficial and invasive procedures.,"['Q9Y5Y9', 'P34995']","Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.",CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C,"Likelidocaine, bupivacaine is an amide local anesthetic that provides local anesthesia through blockade of nerve impulse generation and conduction.These impulses, also known as action potentials, critically depend on membrane depolarization produced by the influx of sodium ions into the neuron through voltage-gated sodium channels.Bupivacaine crosses the neuronal membrane and exerts its anesthetic action through blockade of these channels at the intracellular portion of their pore-forming transmembrane segments.The block is use-dependent, where repetitive or prolonged depolarization increases sodium channel blockade.,Without sodium ions passing through the channel’s pore, bupivacaine stabilizes the membrane at rest and therefore prevents neurotransmission.In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.Clinically, the order of loss of nerve function is as follows: () pain, () temperature, () touch, () proprioception, and () skeletal muscle tone.While it is well-established that the main action of bupivacaine is through sodium channel block, additional analgesic effects of bupivacaine are thought to potentially be due to its binding to the prostaglandin E receptors, subtype EP (PGEEP), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.,TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUProstaglandin E receptor EP subtypeother/unknownHumans","['General Anesthesia', 'Local Anaesthesia therapy', 'Regional nerve block therapy']","['Agents that reduce seizure threshold', 'Amides', 'Amines', 'Anesthetics', 'Anesthetics, Local', 'Anilides', 'Aniline Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Local Anesthesia', 'Local Anesthetics (Amide)', 'Methemoglobinemia Associated Agents', 'Nervous System', 'Neuraxial Anesthetics', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB00887,Bumetanide,"Bumetanideis a sulfamyl diuretic used to treat edema in congestive heart failure, hepatic and renal disease, and nephrotic syndrome.","['Q13621', 'P55011', 'Q9UP95', 'Q9H2X9', 'P13569']","Bumetanide is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in patients in whom high doses of furosemide are ineffective. There is however no reason not to use bumetanide as a first choice drug. The main difference between the two substances is in bioavailability. Bumetanide has more predictable pharmacokinetic properties as well as clinical effect. In patients with normal renal function, bumetanide is 40 times more effective than furosemide.",CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C(O)=O)S(N)(=O)=O,"Bumetanide interferes with renal cAMP and/or inhibits the sodium-potassium ATPase pump. Bumetanide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis.TargetActionsOrganismASolute carrier family member inhibitorHumansASolute carrier family member inhibitorHumansASolute carrier family member inhibitorHumansASolute carrier family member inhibitorHumansUCystic fibrosis transmembrane conductance regulatorantagonistHumans",[],"['Acids, Carbocyclic', 'Agents Causing Muscle Toxicity', 'Amides', 'Aminobenzoates', 'Benzene Derivatives', 'Benzoates', 'Cardiovascular Agents', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'High-Ceiling Diuretics', 'High-Ceiling Diuretics and Potassium-Sparing Agents', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis at Loop of Henle', 'Membrane Transport Modulators', 'meta-Aminobenzoates', 'Natriuretic Agents', 'Nephrotoxic agents', 'Non Potassium Sparing Diuretics', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Photosensitizing Agents', 'Sodium Potassium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB00883,Isosorbide dinitrate,Isosorbide dinitrateis a vasodilator used to treat angina in coronary artery disease.,['P16066'],"Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure.",[H][C@]12OC[C@H](O[N+]([O-])=O)[C@@]1([H])OC[C@H]2O[N+]([O-])=O,"Isosorbide dinitrate is converted to the active nitric oxide to activate guanylate cyclase. This activation increases levels of cyclic guanosine ','-monophosphate (cGMP). cGMP activates protein kinases and causes a series of phosphorylation reactions which leads to dephosphorylation of myosin light chains of smooth muscle fibres. Finally there is a release of calcium ions which causes smooth muscle relaxation and vasodilation.TargetActionsOrganismAAtrial natriuretic peptide receptor agonistHumans",[],"['Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Alcohols', 'Antianginal Agents', 'Carbohydrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Hypotensive Agents', 'Methemoglobinemia Associated Agents', 'Nitrate Vasodilator', 'Nitrates and Nitrites', 'Nitric Oxide Donors', 'Organic Nitrates', 'Sugar Alcohols', 'Vasodilating Agents', 'Vasodilation', 'Vasodilators Used in Cardiac Diseases', 'Vasoprotectives']" +DB00841,Dobutamine,Dobutamineis a beta-1 agonist used to treat cardiac decompensation in patients with organic heart disease or from cardiac surgery.,"['P35348', 'P35368', 'P25100', 'P08588', 'P07550', 'P03372']","Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the beta-adrenoceptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. Dobutamine acts primarily on beta-1 adrenergic receptors, with negligible effects on beta-2 or alpha receptors. It does not cause the release of endogenous norepinephrine, as does dopamine.",CC(CCC1=CC=C(O)C=C1)NCCC1=CC(O)=C(O)C=C1,"Dobutamine directly stimulates beta- receptors of the heart to increase myocardial contractility and stroke volume, resulting in increased cardiac output.TargetActionsOrganismAAlpha- adrenergic receptorsagonistHumansABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUEstrogen receptor alphaNot AvailableHumans",['Intravenous inotropic therapy'],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Adrenergic beta-1 Receptor Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Autonomic Agents', 'Benzene Derivatives', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'Compounds used in a research, industrial, or household setting', 'COMT Substrates', 'Drugs that are Mainly Renally Excreted', 'Ethylamines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Phenols', 'Protective Agents', 'Selective Beta 1-adrenergic Agonists', 'Sympathomimetic (Adrenergic) Agents', 'Sympathomimetics']" +DB00521,Carteolol,"Carteololis a beta adrenergic antagonist used to treat arrhythmia, angina, hypertension, and glaucoma.","['P07550', 'P08588']","Carteolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Carteolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Carteolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce.",CC(C)(C)NCC(O)COC1=CC=CC2=C1CCC(=O)N2,The primary mechanism of the ocular hypotensive action of carteolol in reducing intraocular pressure is most likely a decrease in aqueous humor production. This process is initiated by the non-selective beta and beta adrenergic receptor blockade.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistpartial agonistHumans,[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Autonomic Agents', 'Beta Blocking Agents, Non-Selective', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Negative Inotrope', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Potential QTc-Prolonging Agents', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Sensory Organs', 'Sympatholytics']" +DB00292,Etomidate,Etomidateis a short-acting intravenous anesthetic indicated for the induction of anesthesia and supplementation of subpotent anesthesia during short operative procedures.,"['P14867', 'P18089', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","Etomidate is a non-barbiturate hypnotic that acts at the level of the reticular-activating system to produce anesthesia. Etomidate is an imidazole compound that appears to depress CNS function via GABA. Duration of action is intermediate between thiopental and methohexital, and recovery from a single dose is rapid with little residual depression. Like the barbiturates and propofol, etomidate is does not induce analgesia. Etomidate induces unconsciousness within one circulation time. Recovery is rapid as a result of extensive redistribution and rapid metabolism.",CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1,"Etomidate binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAAlpha-B adrenergic receptoragonistHumansAGABA(A) Receptorpositive allosteric modulatorHumans",['General Anesthesia'],"['Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Hypnotics and Sedatives', 'Imidazoles', 'Nervous System']" +DB00165,Pyridoxine,Pyridoxineis a vitamin used to correct vitamin B6 deficiency and to treat nausea during pregnancy.,['O00764'],"Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.",CC1=C(O)C(CO)=C(CO)C=N1,"Vitamin B is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine '-phosphate (PNP), pyridoxal '-phosphate (PLP) and pyridoxamine '-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B, the term vitamin B is commonly used interchangeably with just one of them, pyridoxine. Vitamin B, principally in its biologically active coenzyme form pyridoxal '-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).TargetActionsOrganismAPyridoxal kinaseligandHumans","['Nutritional supplementation', 'Supplementation', 'Vitamin supplementation', 'Wellness of the Liver']","['Alimentary Tract and Metabolism', 'Analogs/Derivatives', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Diet, Food, and Nutrition', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Food', 'Micronutrients', 'Picolines', 'Pyridines', 'Vitamin B Complex', 'Vitamins']" +DB01085,Pilocarpine,"Pilocarpineis a muscarinic cholinergic agonist used on the eye to treat elevated intraocular pressure, various types of glaucoma, and to induce miosis. Also available orally to treat symptoms of dry mouth associated with Sjogren's syndrome and radiotherapy.","['P20309', 'P11229', 'P08172', 'P08173', 'P08912']","Pilocarpine is a muscarinic agent that mediates diaphoretic, miotic, and central nervous system effects. Pilocarpine stimulates the secretion of various exocrine glands, such as sweat, lacrimal, salivary, and gastrointestinal glands. Following oral administration, pilocarpine increased the mean salivary flow rate by 2- to lO-folds than placebo. Its peak levels were maintained for at least one to two hours.2,7Pilocarpine increases smooth muscle tone, contracts the pupillary and iris sphincter muscles, and induces miosis.2,7,9,10Because pilocarpine may affect all five muscarinic receptor subtypes, it is associated with parasympathetic side effects.1,3",CC[C@H]1[C@@H](CC2=CN=CN2C)COC1=O,"The muscarinic M receptor is expressed in various endocrine and exocrine glands, including the gastric and salivary glands.It is also found in smooth muscle cells in pupillary sphincter and ciliary bodies. The M receptor is a Gq-protein-coupled receptor that activates phospholipase C and upregulates inositol trisphosphate and intracellular calcium. M receptor activation has been implicated in smooth muscle contraction and the stimulation of salivary glands.Pilocarpine is an agonist for M and M receptors,,and is a full and partial agonist at the M receptor.TargetActionsOrganismAMuscarinic acetylcholine receptor MagonistHumansAMuscarinic acetylcholine receptor MagonistHumansAMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor Mpartial agonistHumansUMuscarinic acetylcholine receptor MagonistHumans",[],"['Alkaloids', 'Antiglaucoma Preparations and Miotics', 'Autonomic Agents', 'Cholinergic Agents', 'Cholinergic Agonists', 'Cholinergic Receptor Agonist', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strong)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Miotics', 'Muscarinic Agonists', 'Nervous System', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Parasympathomemetic (Cholinergic) Agents', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Sensory Organs']" +DB00186,Lorazepam,"Lorazepamis a short-acting benzodiazepine commonly used to treat panic disorders, severe anxiety, and seizures.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required.8The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect.9The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.10",OC1N=C(C2=CC=CC=C2Cl)C2=C(NC1=O)C=CC(Cl)=C2,"Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane.According to the binding site of lorazepam, we can observe different activities as the binding in the amygdala is known to help mainly in anxiety disorders while the binding in the cerebral cortex helps in seizure disorders.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",['Anesthetic premedication therapy'],"['Anti-Anxiety Agents', 'Anticonvulsants', 'Antiemetics', 'Autonomic Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00503,Ritonavir,Ritonaviris an HIV protease inhibitor used in combination with other antivirals in the treatment of HIV infection.,"['Q72874', 'O75469']",Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Ritonavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Modern protease inhibitors require the use of low-dose ritonavir to boost pharmacokinetic exposure through inhibition of metabolism via the cytochrome P450 3A4 enzyme pathway.,CC(C)[C@H](NC(=O)N(C)CC1=CSC(=N1)C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)OCC1=CN=CS1)CC1=CC=CC=C1,"Ritonavic inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such asgagandpol.Gagencodes proteins involved in the core and the nucleocapsid, whilepolencodes the the HIV reverse transcriptase, ribonuclease H, integrase, and protease. Thepol-encoded proteins are initially translated in the form of a larger precursoe polypeptide,gag-pol, and needs to be cleaved by HIV protease to form other complement proteins. Ritonavir prevents the cleavage of thegag-polpolyprotein, which results in noninfectious, immature viral particles. Ritonavir is a potent inhibitor of cytochrome P CYPA isoenzyme present both in the intestinal tract and liver. It is a type II ligand that perfectly fits into the CYPA active site cavity and irreversibly binds to the heme iron via the thiazole nitrogen, which decreases the redox potential of the protein and precludes its reduction with the redox partner, cytochrome P reductase. Ritonavir may also play a role in limiting cellular transport and efflux of other protease inhibitors via the P-glycoprotein and MRP efflux channels.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus UNuclear receptor subfamily group I member activatorHumans",[],"['Acids, Acyclic', 'Agents Causing Muscle Toxicity', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'Antivirals used in combination for the treatment of HIV infections', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (weak)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Experimental Unapproved Treatments for COVID-19', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Protease Inhibitors', 'QTc Prolonging Agents', 'Sulfur Compounds', 'Thiazoles', 'Treatments for Hepatitis C', 'UDP Glucuronosyltransferases Inducers', 'UGT1A1 Inducers', 'Viral Protease Inhibitors']" +DB00197,Troglitazone,Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded bypioglitazoneandrosiglitazone.,"['P37231', 'P62508', 'P11474', 'Q03181', 'Q07869', 'P09211', 'O60488', 'P05121', 'Q99808']","Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control.",CC1=C(C)C2=C(CCC(C)(COC3=CC=C(CC4SC(=O)NC4=O)C=C3)O2)C(C)=C1O,"Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPARα and PPARγ, with a highter affinity for PPARγ. The drug also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). Unlike sulfonylureas, troglitazone is not an insulin secretagogue.TargetActionsOrganismAPeroxisome proliferator-activated receptor gammaagonistregulatorHumansNEstrogen-related receptor gammainverse agonistHumansNSteroid hormone receptor ERRinverse agonistHumansUPeroxisome proliferator-activated receptor deltaNot AvailableHumansUPeroxisome proliferator-activated receptor alphaNot AvailableHumansUGlutathione S-transferase PNot AvailableHumansNLong-chain-fatty-acid--CoA ligase inhibitorHumansUPlasminogen activator inhibitor antagonistHumansNEquilibrative nucleoside transporter inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Benzopyrans', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Inhibitors', 'Chromans', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Heterocyclic Compounds, Fused-Ring', 'OATP1B1/SLCO1B1 Inhibitors', 'Oral Hypoglycemics', 'Pyrans', 'Sulfur Compounds', 'Thiazoles', 'Thiazolidinediones', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A4 substrates', 'UGT1A6 Inhibitors', 'UGT1A6 substrate', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB00599,Thiopental,"Thiopentalis a barbiturate used to induce general anesthesia, treat convulsions, and reduce intracranial pressure.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P43681', 'P36544', 'P42262', 'Q13002', 'O00519', 'P20309']","Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia",CCCC(C)C1(CC)C(=O)NC(=S)NC1=O,"Thiopental binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumansUFatty-acid amide hydrolase inhibitorHumansUMuscarinic acetylcholine receptor MNot AvailableHumans",[],"['Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Anticholinergic Agents', 'Anticonvulsants', 'Barbiturates', 'Barbiturates, Plain', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Hypotensive Agents', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones', 'Thiobarbiturates']" +DB00975,Dipyridamole,Dipyridamoleis a phosphodiesterase inhibitor used to prevent postoperative thromboembolic events.,"['Q9Y233', 'O76074', 'P27815', 'P00813', 'P53805', 'P02763']","Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis.",OCCN(CCO)C1=NC2=C(N=C(N=C2N2CCCCC2)N(CCO)CCO)C(=N1)N1CCCCC1,"Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation.TargetActionsOrganismAcAMP and cAMP-inhibited cGMP ','-cyclic phosphodiesterase AinhibitorHumansAcGMP-specific ','-cyclic phosphodiesteraseinhibitorHumansAcAMP-specific ','-cyclic phosphodiesterase AinhibitorHumansAAdenosine deaminaseinhibitorHumansUCalcipressin-Not AvailableHumansUAlpha--acid glycoprotein Not AvailableHumans",['Anti-platelet Therapy'],"['Anticoagulants', 'Antiplatelet agents', 'Blood and Blood Forming Organs', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Decreased Platelet Aggregation', 'Enzyme Inhibitors', 'Hematologic Agents', 'Hypotensive Agents', 'Miscellaneous Vasodilatating Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Pyrimidines', 'Vasodilating Agents']" +DB00761,Potassium chloride,Potassium chlorideis a potassium salt used to treat hypokalemia.,"['P55011', 'Q13621', 'Q9H2X9', 'Q9UHW9', 'Q9Y666', 'Q9UP95']","The potassium ion is in the principle intracellular cation of most body tissues. Potassium ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity, the transmission of nerve impulses, the contraction of cardiac, skeletal and smooth muscle, and the maintenance of normal renal function. The intracellular concentration of potassium is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane. Potassium is a normal dietary constituent and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of potassium is 50 to 100 mEq per day. Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primarily or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Potassium depletion may produce weakness, fatigue, disturbances of cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and, in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine. If potassium depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, e.g., where the patient requires long-term diuretic therapy, supplemental potassium in the form of high potassium food or potassium chloride may be able to restore normal potassium levels. In rare circumstances (e.g., patients with renal tubular acidosis) potassium depletion may be associated with metabolic acidosis and hyperchloremia. In such patients, potassium replacement should be accomplished with potassium salts other than the chloride, such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.",[Cl-].[K+],Supplemental potassium in the form of high potassium food or potassium chloride may be able to restore normal potassium levels.TargetActionsOrganismUSolute carrier family member Not AvailableHumansUSolute carrier family member binderHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumansUSolute carrier family member Not AvailableHumans,"['Acid- Base Balance', 'Bowel preparation therapy', 'Electrolyte replacement', 'Fluid replacement therapy', 'Haemofiltration', 'Hemodialysis Treatment', 'Parenteral Nutrition', 'Parenteral rehydration therapy', 'Plasma Volume Replacement', 'Urine alkalinization therapy', 'Fluid and electrolyte maintenance therapy']","['Agents causing hyperkalemia', 'Alimentary Tract and Metabolism', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Chlorides', 'Chlorine Compounds', 'Drugs that are Mainly Renally Excreted', 'Electrolyte Solutions', 'Hemodialysis Solution', 'I.V. Solution Additives', 'Mineral Supplements', 'Minerals', 'Potassium Compounds', 'Potassium Salt', 'Replacement Preparations']" +DB00867,Ritodrine,Ritodrineis an adrenergic beta agonist used to treat premature labor.,"['P07550', 'P08588', 'P07550', 'P13945', 'P48048', 'P78508', 'Q14654', 'Q14500', 'Q9UNX9', 'Q99712', 'Q15842', 'P98194', 'O75185', 'P20020', 'Q01814', 'Q16720', 'P23634', 'O14983', 'P16615', 'Q12791', 'Q16558', 'Q9Y691', 'Q9NPA1', 'Q86W47', 'O15554', 'Q92952', 'Q9H2S1', 'Q9UGI6', 'Q15746', 'O75897']","Beta-2 adrenergic receptors are located at sympathetic neuroeffector junctions of many organs, including uterus. Ritodrine is beta-2 adrenergic agonist. It stimulates beta-2 adrenergic receptor, increases cAMP level and decreases intracellular calcium concentration. The decrease of calcium concentration leads to a relaxation of uterine smooth muscle and, therefore, a decrease in premature uterine contractions.",C[C@@H](NCCC1=CC=C(O)C=C1)[C@@H](O)C1=CC=C(O)C=C1,"Ritodrine is beta- adrenergic agonist. It binds to beta- adrenergic receptors on outer membrane of myometrial cell, activates adenyl cyclase to increase the level of cAMP which decreases intracellular calcium and leads to a decrease of uterine contractions.TargetActionsOrganismABeta- adrenergic receptoragonistHumansABeta adrenergic receptoragonistdownregulatorHumansAATP-sensitive potassium channelactivatorHumansUCalcium transporting ATPasesinhibitorHumansACalcium-activated potassium channelactivatorHumansUMyosin light chain kinase, smooth muscleinhibitorHumansUSulfotransferase CsubstrateHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Autonomic Agents', 'Ethylamines', 'Genito Urinary System and Sex Hormones', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Propanolamines', 'Propanols', 'Reproductive Control Agents', 'Sympathomimetics', 'Sympathomimetics, Labour Repressants', 'Tocolytic Agents']" +DB00171,ATP,An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.,"['O95255', 'O15439', 'P33527', 'P13569', 'P42336', 'P68400', 'P67870', 'Q96G91', 'P53041', 'P42684', 'O95477', 'Q9NR19', 'Q9UM73', 'Q13564', 'Q13131', 'P10398', 'P37023', 'P33121', 'P49902', 'O43681', 'O60706', 'P31749', 'P25098', 'O14727', 'Q9NUB1', 'P36896', 'Q04771', 'O95342', 'P08243', 'Q96Q40', 'P12235', 'Q09428', 'P00966', 'Q9Y4W6', 'P35626', 'Q16671', 'Q07912', 'P00519', 'Q08828', 'P08183', 'P45844', 'Q92887']","Adenosine triphosphate (ATP) is the nucleotide known in biochemistry as the ""molecular currency"" of intracellular energy transfer; that is, ATP is able to store and transport chemical energy within cells. ATP also plays an important role in the synthesis of nucleic acids. The total quantity of ATP in the human body is about 0.1 mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis.",NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O,"ATP is able to store and transport chemical energy within cells. ATP also plays an important role in the synthesis of nucleic acids. ATP can be produced by various cellular processes, most typically in mitochondria by oxidative phosphorylation under the catalytic influence of ATP synthase. The total quantity of ATP in the human body is about . mole. The energy used by human cells requires the hydrolysis of to moles of ATP daily. This means that each ATP molecule is recycled to times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis.TargetActionsOrganismUMultidrug resistance-associated protein Not AvailableHumansUMultidrug resistance-associated protein Not AvailableHumansUMultidrug resistance-associated protein Not AvailableHumansUCystic fibrosis transmembrane conductance regulatorcofactorHumansUPhosphatidylinositol ,-bisphosphate -kinase catalytic subunit alpha isoformNot AvailableHumansUCasein kinase II subunit alphaNot AvailableHumansUCasein kinase II subunit betaNot AvailableHumansUPY purinoceptor Not AvailableHumansUSerine/threonine-protein phosphatase Not AvailableHumansUTyrosine-protein kinase ABLinhibitorHumansUATP-binding cassette sub-family A member Not AvailableHumansUAcetyl-coenzyme A synthetase, cytoplasmicNot AvailableHumansUALK tyrosine kinase receptorNot AvailableHumansUNEDD-activating enzyme E regulatory subunitNot AvailableHumansU'-AMP-activated protein kinase catalytic subunit alpha-Not AvailableHumansUSerine/threonine-protein kinase A-RafNot AvailableHumansUSerine/threonine-protein kinase receptor RNot AvailableHumansULong-chain-fatty-acid--CoA ligase Not AvailableHumansUCytosolic purine '-nucleotidaseNot AvailableHumansUATPase ASNANot AvailableHumansUATP-binding cassette sub-family C member Not AvailableHumansURAC-alpha serine/threonine-protein kinaseNot AvailableHumansUBeta-adrenergic receptor kinase Not AvailableHumansUApoptotic protease-activating factor Not AvailableHumansUAcetyl-coenzyme A synthetase -like, mitochondrialNot AvailableHumansUActivin receptor type-BNot AvailableHumansUActivin receptor type-Not AvailableHumansUBile salt export pumpNot AvailableHumansUAsparagine synthetase [glutamine-hydrolyzing]Not AvailableHumansUCyclin-dependent kinase Not AvailableHumansUADP/ATP translocase Not AvailableHumansUATP-binding cassette sub-family C member Not AvailableHumansUArgininosuccinate synthaseNot AvailableHumansUAFG-like protein Not AvailableHumansUBeta-adrenergic receptor kinase Not AvailableHumansUAnti-Muellerian hormone type- receptorNot AvailableHumansUActivated CDC kinase Not AvailableHumansUTyrosine-protein kinase ABLinhibitorHumansUAdenylate cyclase type Not AvailableHumansUP-glycoprotein Not AvailableHumansUATP-binding cassette sub-family G member Not AvailableHumansUCanalicular multispecific organic anion transporter Not AvailableHumans",[],"['Adenine Nucleotides', 'Adenosine Triphosphate', 'Dietary Supplements', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleotides', 'Purine Nucleotides', 'Purines', 'Ribonucleotides', 'Supplements']" +DB00649,Stavudine,Stavudineis a dideoxynucleoside used in the treatment of HIV infection.,['Q72547'],"Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.",CC1=CN([C@@H]2O[C@H](CO)C=C2)C(=O)NC1=O,Stavudine inhibits the activity of HIV- reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ,[],"['Agents Causing Muscle Toxicity', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'Deoxyribonucleosides', 'Dideoxynucleosides', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Neurotoxic agents', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'OAT1/SLC22A6 Substrates', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Reverse Transcriptase Inhibitors', 'Toxic Actions']" +DB01356,Lithium cation,Lithium cationis a drug used for the management of bipolar disorder and other psychiatric conditions.,"['P49841', 'P29218', 'O14732', 'P42263']","Although lithium has been used for over 50 years in treatment of bipolar disorder, the mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors.",[Li+],"The precise mechanism of action of Li+ as a mood-stabilizing agent is currently unknown. It is possible that Li+ produces its effects by interacting with the transport of monovalent or divalent cations in neurons. An increasing number of scientists have come to the conclusion that the excitatory neurotransmitter glutamate is the key factor in understanding how lithium works. Lithium has been shown to change the inward and outward currents of glutamate receptors (especially GluR), without a shift in reversal potential. Lithium has been found to exert a dual effect on glutamate receptors, acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little. It is postulated that too much glutamate in the space between neurons causes mania, and too little, depression. Another mechanism by which lithium might help to regulate mood include the non-competitive inhibition of an enzyme called inositol monophosphatase. Alternately lithium's action may be enhanced through the deactivation of the GSK-B enzyme. The regulation of GSK-B by lithium may affect the circadian clock. GSK- is known for phosphorylating and thus inactivating glycogen synthase. GSK-B has also been implicated in the control of cellular response to damaged DNA. GSK- normally phosphorylates beta catenin, which leads to beta catenin degratation. When GSK- is inhibited, beta catenin increases and transgenic mice with overexpression of beta catenin express similar behaviour to mice treated with lithium. These results suggest that increase of beta catenin may be a possible pathway for the therapeutic action of lithium.TargetActionsOrganismUGlycogen synthase kinase- betainhibitorHumansUInositol monophosphatase inhibitorHumansUInositol monophosphatase inhibitorHumansUGlutamate receptor potentiatorHumans",[],"['Antidepressive Agents', 'Antimanic Agents', 'Antipsychotic Agents', 'Central Nervous System Depressants', 'Highest Risk QTc-Prolonging Agents', 'Lithium Compounds', 'Mood Stabilizer', 'Nephrotoxic agents', 'Neurotoxic agents', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01001,Salbutamol,"Salbutamolis a beta-2 adrenergic receptor agonist used to treat asthma, bronchitis, COPD, as well as prevent exercise induced bronchospasms.","['P07550', 'P08588', 'P13945']","Salbutamol (INN) or albuterol (USAN), a moderately selective beta(2)-receptor agonist similar in structure to terbutaline, is widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases.Label,4,5The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity.2The R-enantiomer is available and sold in its pure form as levalbuterol and subsequently may produce fewer side-effects with only the R-enantiomer present - although this has not been formally demonstrated.2After oral and parenteral administration, stimulation of the beta receptors in the body, both beta-1 and beta-2, occurs because (a) beta-2 selectivity is not absolute, and (b) higher concentrations of salbutamol occur in the regions of these receptors with these modes of administration.Label,4,5This results in the beta-1 effect of cardiac stimulation, though not so much as with isoprenaline, and beta-2 effects of peripheral vasodilatation and hypotension, skeletal muscle tremor, and uterine muscle relaxation.Label,4,5Metabolic effects such as hyperinsulinemia and hyperglycemia also may occur, although it is not known whether these effects are mediated by beta-1 or beta-2 receptors.Label,4,5The serum potassium levels have a tendency to fall.4",CC(C)(C)NCC(O)C1=CC(CO)=C(O)C=C1,"In vitro studies and in vivo pharmacologic studies have shown that salbutamol has a preferential effect on beta-adrenergic receptors compared with isoproterenol.Label,,Although beta­ adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta adrenoceptors are the predominant receptors in the heart, there are also beta-adrenoceptors in the human heart comprising % to % of the total beta-adrenoceptors.Label,,The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta-agonists may have cardiac effects.Label,,Activation of beta-adrenergic receptors on airway smooth muscle leads to the activation of adenyl cyclase and to an increase in the intracellular concentration of cyclic-′,′-adenosine monophosphate (cyclic AMP).Label,,This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation.Label,,Salbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles.Label,,Salbutamol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges.Label,,Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway.Label,,Salbutamol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects.Label,,Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes.Label,,A measurable decrease in airway resistance is typically observed within to minutes after inhalation of salbutamol.Label,,The maximum improvement in pulmonary function usually occurs to minutes after salbutamol treatment, and significant bronchodilator activity has been observed to persist for to hours.Label,,TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUBeta- adrenergic receptorNot AvailableHumans","['Airway secretion clearance therapy', 'Bronchodilation']","['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Ethanolamines', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Reproductive Control Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetic (Adrenergic) Agents', 'Tocolytic Agents']" +DB00863,Ranitidine,"Ranitidineis a histamine H2 antagonist used to treat duodenal ulcers, Zollinger-Ellison syndrome, gastric ulcers, GERD, and erosive esophagitis.","['P25021', 'P22303']","Ranitidine decreases the secretion of gastric acid stimulated by food and drugs. It also reduces the secretion of gastric acid in hypersecretory conditions such as Zollinger-Ellison syndrome.6,11Marked improvements in the appearance of the esophageal tissues have been observed by endoscopic imaging after ranitidine therapy.5,11",CNC(NCCSCC1=CC=C(CN(C)C)O1)=C[N+]([O-])=O,"After a meal, the hormone gastrin, produced by cells in the lining of the stomach, stimulates the release of histamine, which then binds to histamine H receptors, leading to the secretion of gastric acid. Ranitidine reduces the secretion of gastric acid by reversible binding to histamine (H) receptors, which are found on gastric parietal cells. This process leads to the inhibition of histamine binding to this receptor, causing the reduction of gastric acid secretion. The relief of gastric-acid related symptoms can occur as soon as minutes after administration of a single dose, and the effects can last from - hours, providing fast and effective symptomatic relief.,,TargetActionsOrganismAHistamine H receptorantagonistHumansUAcetylcholinesteraseinhibitorHumans",[],"['Acid Reducers', 'Agents Causing Muscle Toxicity', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Furans', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Histamine Antagonists', 'Histamine H2 Antagonists', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Substrates', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates']" +DB01236,Sevoflurane,Sevofluraneis a inhalation anaesthetic agent used for induction and maintenance of general anesthesia during surgical procedures.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P23415', 'P42261', 'P98194', 'O75185', 'P20020', 'Q01814', 'Q16720', 'P23634', 'O14983', 'P16615', 'P03886', 'Q96ER9']","Sevoflurane induces muscle relaxation and reduces sensitivity by altering tissue excitability with a fast onset of action. It does so by decreasing the extent of gap junction-mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.6Compared tohalothaneandisoflurane, sevoflurane has a shorter emergence time, as well as a shorter time to first analgesia.8To reach an equilibrium between alveolar and arterial partial pressure, only a minimal amount of sevoflurane needs to be dissolved in blood.8The use of sevoflurane can increase the risk of renal injury, respiratory depression, and QT prolongation. Also, it can lead to malignant hyperthermia, perioperative hyperkalemia, and pediatric neurotoxicity. Episodes of severe bradycardia and cardiac arrest have been reported in pediatric patients with Down Syndrome given sevoflurane. Sevoflurane anesthesia may impair the performance of activities requiring mental alertness, such as driving or operating machinery.8",FCOC(C(F)(F)F)C(F)(F)F,"The precise mechanism of action of sevoflurane has not been fully elucidated. Like other halogenated inhalational anesthetics, sevoflurane induces anesthesia by binding to ligand-gated ion channels and blocking CNS neurotransmission. It has been suggested that inhaled anesthetics enhance inhibitory postsynaptic channel activity by binding GABAAand glycine receptors, and inhibit excitatory synaptic channel activity by binding nicotinic acetylcholine, serotonin, and glutamate receptors.Sevoflurane has an effect on several ionic currents, including the hyperpolarisation-activated cation current (If), the T-type and L-type Ca+currents (ICa, Tand ICa, L), the slowly activating delayed rectifier K+currents (IKs), and the Na+/Ca+exchange current (INCX).This ability to modulate ion channel activity can also regulate cardiac excitability and contractility.TargetActionsOrganismAGABA(A) ReceptoragonistHumansAGlycine receptor subunit alpha-agonistHumansAGlutamate receptor antagonistHumansACalcium transporting ATPasesinhibitorHumansUNADH-ubiquinone oxidoreductase chain inhibitorHumansAMitochondrial potassium channelactivatorHumans","['General Anesthesia', 'Induction and Maintenance of General Anesthesia']","['Agents that produce hypertension', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Inhalation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Ethers', 'Hydrocarbons, Fluorinated', 'Hydrocarbons, Halogenated', 'Hypotensive Agents', 'Methyl Ethers', 'Nervous System', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00443,Betamethasone,"Betamethasoneis a systemic corticosteroid used to relieve inflammation in various conditions, including but not limited to allergic states, dermatologic disorders, gastrointestinal diseases, and hematological disorders.",['P04150'],"Corticosteroids bind to the glucocorticoid receptor inhibiting pro-inflammatory signals, while promoting anti-inflammatory signals.1Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.1Patients who require long-term treatment with a corticosteroid should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.1",[H][C@@]12C[C@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Glucocorticoids inhibit neutrophil apoptosis and demargination, and inhibit NF-Kappa B and other inflammatory transcription factors.They also inhibit phospholipase A, leading to decreased formation of arachidonic acid derivatives.In addition, glucocorticoids promote anti-inflammatory genes like interleukin-.Corticosteroids like betamethasone can act through nongenomic and genomic pathways.The genomic pathway is slower and occurs when glucocorticoids activate glucocorticoid receptors and initiate downstream effects that promote transcription of anti-inflammatory genes including phosphoenolpyruvate carboxykinase (PEPCK), IL--receptor antagonist, and tyrosine amino transferase (TAT).On the other hand, the nongenomic pathway is able to elicit a quicker response by modulating T-cell, platelet and monocyte activity through the use of existing membrane-bound receptors and second messengers.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents Causing Muscle Toxicity', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Alimentary Tract and Metabolism', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids Acting Locally', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs for Obstructive Airway Diseases', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'Nasal Preparations', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Otologicals', 'P-glycoprotein substrates', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Respiratory System Agents', 'Steroids', 'Steroids, Fluorinated', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroxine-binding globulin inhibitors', 'Vasoprotectives']" +DB00152,Thiamine,Thiamineis a vitamin used to correct vitamin B1 deficiency.,['Q9H3S4'],"Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.",CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N,"It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions.TargetActionsOrganismAThiamin pyrophosphokinase substrateHumans","['Nutritional supplementation', 'Vitamin supplementation', 'Dietary supplementation']","['Alimentary Tract and Metabolism', 'Diet, Food, and Nutrition', 'Food', 'Growth Substances', 'Micronutrients', 'OCT1 substrates', 'OCT2 Inhibitors', 'Physiological Phenomena', 'Pyrimidines', 'Sulfur Compounds', 'Thiazoles', 'Vitamin B Complex', 'Vitamins']" +DB00244,Mesalazine,Mesalazineis an aminosalicylate drug used to treat mild to moderate active ulcerative colitis and also to maintain remission once achieved.,"['P35354', 'P23219', 'P09917', 'P37231', 'O15111', 'O14920', 'P35228']","Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter responsible for most of the side effects associated with sulphasalazine therapy, while mesalazine is known to be the active moiety in the treatment of ulcerative colitis12.Mesalazine is thought to dampen the inflammatory process through its ability to inhibit prostaglandin synthesis, interfere with leukotriene synthesis, and consequent leukocyte migration as well as act as a potent scavenger of free radicals.25Regardless of the mode of action, mesalazine appears to be active mainly topically rather than systemically.25Intraperitoneally administered mesalazine at 30 and 340 mg/kg daily had similar efficacy in attenuating colitis as prednisolone 4 to 550 mg/kg daily given intraperitoneally or sulphasalazine 0.34 to 5 mg/kg given orally in immune complex-induced colitis mice.11Mesalazine at 5 mmol/L and sulphasalazine 1.5 mmol/L also reversed the increase in water and chloride secretion and decrease the sodium in dinitrochlorbenzene-induced colitis guinea pig.11",NC1=CC(C(O)=O)=C(O)C=C1,"Although the mechanism of action of mesalazine is not fully understood, it is believed to possess a topical anti-inflammatory effect on colonic epithelial cells.Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.Furthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NFkB) and consequently the production of key pro-inflammatory cytokines.,,It has been proposed that reduced expression of PPAR gamma nuclear receptors (gamma form of peroxisome proliferator-activated receptors) may be implicated in ulcerative colitis, and that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium.,,,Other research also showed the potential involvement of inducible NO synthase (iNOS) and that mesalazine can inhibit this enzyme to amiliorate the enteropathy in inflammatory bowel diseases.Moreover, since increased leukocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B, and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease it is also believed that mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leukocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansAArachidonate -lipoxygenaseinhibitorHumansAPeroxisome proliferator-activated receptor gammaagonistHumansUInhibitor of nuclear factor kappa-B kinase subunit alphainhibitorHumansUInhibitor of nuclear factor kappa-B kinase subunit betainhibitorHumansUNitric oxide synthase, inducibleinhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Aminosalicylate', 'Aminosalicylic Acids', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Benzene Derivatives', 'Hydroxybenzoates', 'Intestinal Antiinflammatory Agents', 'Nephrotoxic agents', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'OATP2B1/SLCO2B1 substrates', 'Phenols', 'Salicylates']" +DB01213,Fomepizole,Fomepizoleis an inhibitor of alcohol dehydrogenase used as an antidote in confirmed or suspected methanol or ethylene glycol poisoning.,"['P07327', 'P00325', 'P00326', 'P04040']","Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycoaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. Glycolate and oxalate are primarily responsible for metabolic acidosis and renal damage seen in ethylene glycol toxicity. {01}{03} Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning.",CC1=CNN=C1,Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.TargetActionsOrganismAAlcohol dehydrogenase AinhibitorHumansAAlcohol dehydrogenase BinhibitorHumansAAlcohol dehydrogenase CinhibitorHumansACatalaseinhibitorHumans,[],"['Antidotes', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Protective Agents', 'Pyrazoles']" +DB00703,Methazolamide,Methazolamideis a carbonic anhydrase inhibitor used to treat open angle glaucoma and acute angle closure glaucoma.,"['P00915', 'P22748', 'P00918', 'P43166', 'P07451']","Methazolamide is topical carbonic anhydrase inhibitor. Methazolamide is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers. Methazolamide is a sulfonamide derivative; however, it does not have any clinically significant antimicrobial properties. Although methazolamide achieves a high concentration in the cerebrospinal fluid, it is not-considered an effective anticonvulsant. Methazolamide has a weak and transient diuretic effect, therefore use results in an increase in urinary volume, with excretion of sodium, potassium and chloride.",CN1N=C(S\C1=N\C(C)=O)S(N)(=O)=O,"Methazolamide is a potent inhibitor of carbonic anhydrase. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport.TargetActionsOrganismACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Antiglaucoma Preparations and Miotics', 'Carbonic Anhydrase Inhibitors', 'Cardiovascular Agents', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypotensive Agents', 'Natriuretic Agents', 'OAT1/SLC22A6 inhibitors', 'Ophthalmologicals', 'Photosensitizing Agents', 'Sensory Organs', 'Sulfonamides', 'Sulfur Compounds', 'Thiadiazoles', 'Thiazoles']" +DB00573,Fenoprofen,Fenoprofenis an anti-inflammatory analgesic used to treat mild to moderate pain in addition to the signs and symptoms of rheumatoid arthritis and osteoarthritis.,"['P35354', 'Q07869', 'P37231', 'P23219']","Fenoprofen is a propionic acid derivative with analgesic, antiinflammatory and antipyretic properties. Fenoprofen inhibits prostaglandin synthesis by decreasing the enzyme needed for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory action of fenoprofen has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenoprofen have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints. In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown fenoprofen to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with fenoprofen than in aspirin-treated patients. It is not known whether fenoprofen causes less peptic ulceration than does aspirin. In patients with pain, the analgesic action of fenoprofen has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect.",CC(C(O)=O)C1=CC(OC2=CC=CC=C2)=CC=C1,"Fenoprofen's exact mode of action is unknown, but it is thought that prostaglandin synthetase inhibition is involved. Fenoprofen has been shown to inhibit prostaglandin synthetase isolated from bovine seminal vesicles.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUPeroxisome proliferator-activated receptor alphaactivatorHumansUPeroxisome proliferator-activated receptor gammaNot AvailableHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Phenylpropionates', 'Propionates', 'Sensory System Agents']" +DB00543,Amoxapine,Amoxapineis a tricyclic antidepressant used in the treatment of neurotic or reactive depressive disorders and endogenous or psychotic depression.,"['P31645', 'P23975', 'P14416', 'P21728', 'P08913', 'P35348', 'P11229', 'P14867', 'P28223', 'P28335', 'P50406', 'P34969', 'P35462', 'P21917', 'P35367', 'P35348', 'P35368', 'P25100', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P41595', 'P46098', 'P08908', 'P28222', 'P08913', 'P18089', 'P18825', 'Q9H3N8', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'Q01959']","Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine",ClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C1,Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (-HT).TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansUSodium-dependent noradrenaline transporterinhibitorHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUGamma-aminobutyric acid receptor subunit alpha-antagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor antagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUHistamine H receptorantagonistHumansUAlpha- adrenergic receptorsantagonistHumansUMuscarinic acetylcholine receptorantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumansUAlpha- adrenergic receptorsantagonistHumansUHistamine H receptorbinderHumansUGABA(A) ReceptorbinderHumansUSodium-dependent dopamine transporterbinderHumans,[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tetracyclic', 'Antidepressive Agents, Tricyclic', 'Antipsychotic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dibenzoxazepines', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists']" +DB00373,Timolol,Timololis a non-selective beta adrenergic blocker used in the treatment of elevated intraocular pressure in ocular hypertension or open angle glaucoma.,"['P08588', 'P07550', 'P00720']","Timolol, when administered by the ophthalmic route, rapidly reduces intraocular pressure. When administered in the tablet form, it reduces blood pressure, heart rate, and cardiac output, and decreases sympathetic activity.1,2,3,17. This drug has a fast onset of action, usually occurring within 20 minutes of the administration of an ophthalmic dose. Timolol maleate can exert pharmacological actions for as long as 24 hours if given in the 0.5% or 0.25% doses.23",[H][C@](O)(CNC(C)(C)C)COC1=NSN=C1N1CCOCC1,"Timolol competes with adrenergic neurotransmitters for binding to beta()-adrenergic receptors in the heart and the beta()-receptors in the vascular and bronchial smooth muscle. This leads to diminished actions of catecholamines, which normally bind to adrenergic receptors and exert sympathetic effects leading to an increase in blood pressure and heart rate.Beta()-receptor blockade by timolol leads to a decrease in both heart rate and cardiac output during rest and exercise, and a decrease in both systolic and diastolic blood pressure.,In addition to this, a reduction in reflex orthostatic hypotension may also occur. The blockade of beta() receptors by timolol in the blood vessels leads to a decrease in peripheral vascular resistance, reducing blood pressure.,,The exact mechanism by which timolol reduces ocular pressure is unknown at this time, however, it likely decreases the secretion of aqueous humor in the eye.According to one study, the reduction of aqueous humor secretion may occur through the decreased blood supply to the ciliary body resulting from interference with the active transport system or interference with prostaglandin biosynthesis.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumansULysozymeNot AvailableEnterobacteria phage T",[],"['Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Non-Selective', 'Beta Blocking Agents, Non-Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'EENT Drugs, Miscellaneous', 'Hypotensive Agents', 'Morpholines', 'Ophthalmologicals', 'Oxazines', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Sulfur Compounds', 'Thiadiazoles', 'Thiazoles']" +DB01016,Glyburide,Glyburideis a sulfonylurea used in the treatment of non insulin dependent diabetes mellitus.,"['Q09428', 'Q14654', 'O60706', 'O95342', 'O95477', 'Q14654', 'Q15842', 'P50416', 'P13569', 'Q8TD43']","Glyburide is a second generation sulfonylurea8that stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations.7Glibenclamide has a long duration of action as it is given once daily, and a wide therapeutic index as patients are started at doses as low as 0.75mg but that can increase as high as 10mg or more.9,12Patients taking glyburide should be cautioned regarding an increased risk of cardiovascular mortality as seen with tolbutamide, another sulfonylurea.12",COC1=C(C=C(Cl)C=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1,"Glyburide belongs to a class of drugs known as sulfonylureas.These drugs act by closing ATP-sensitive potassium channels on pancreatic beta cells.The ATP-sensitive potassium channels on beta cells are known as sulfonylurea receptor (SUR).Under low glucose concentrations, SUR remains open, allowing for potassium ion efflux to create a -mV membrane potential.Normally SUR closes in response to high glucose concentrations, the membrane potential of the cells becomes less negative, the cell depolarizes, voltage gated calcium channels open, calcium ions enter the cell, and the increased intracellular calcium concentration stimulates the release of insulin containing granules.Glyburide bypasses this process by forcing SUR closed and stimulating increased insulin secretion.TargetActionsOrganismASulfonylurea receptor , Kir.blockerHumansUATP-binding cassette sub-family C member modulatorHumansUBile salt export pumpinhibitorHumansUATP-binding cassette sub-family A member inhibitorHumansUMitochondrial ATP-sensitive potassium channelinhibitorHumansUCarnitine O-palmitoyltransferase , liver isoforminhibitorHumansUCystic fibrosis transmembrane conductance regulatorantagonistHumansUTransient receptor potential cation channel subfamily M member inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'BCRP/ABCG2 Substrates', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs Used in Diabetes', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'OAT1/SLC22A6 inhibitors', 'OATP2B1/SLCO2B1 substrates', 'Oral Hypoglycemics', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB00363,Clozapine,Clozapineis an atypical or second-generation antipsychotic drug used in treatment-resistant schizophrenia and to decrease suicide risk in schizophrenic patients.,"['P21728', 'P14416', 'P35462', 'P21917', 'P21918', 'P08908', 'P28222', 'P28221', 'P28566', 'P28223', 'P46098', 'P28335', 'P50406', 'P34969', 'P18825', 'P35367', 'Q9H3N8', 'P35348', 'P35368', 'P08913', 'P18089', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'Q9NYX4', 'P09211', 'Q9UBS5', 'O75899', 'P14867', 'P18505', 'Q8N1C3']","Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives that is universally regarded as the treatment of choice for treatment-resistant schizophrenia.22Although it is thought to mediate its pharmacological effect through antagonism of the dopamine type 2 (D2) and the serotonin type 2A (5-HT2A) receptors, research have shown that clozapine can act on various types of receptors.21Patients should be counseled regarding the risk of hypersensitivity reactions such as agranulocytosis and myocarditis with clozapine use.27Clozapine-induced agranulocytosis, which is a reduction in the absolute neutrophil count or white blood cell count, places the patient at an increased risk for infection.8,27Agranulocytosis is most likely to occur in the first 3-6 months of therapy, but it can still occur after years of treatment. The mechanism is thought to be a dose-independent and immune-mediated reaction against neutrophils.6Patients are strictly monitored by lab testing (complete blood count with differential) to ensure agranulocytosis is detected and treated if it occurs.27Testing is initially completed at one-week intervals but is expanded to two-week intervals at six months, and then four-week intervals at twelve months if lab results have been within an appropriate range. Monitoring parameters may change if there is any break in therapy. In Canada, the patient's lab values are reported to the manufacturer for hematological monitoring, and in the USA, the patient's lab values are reported to the REMS (Risk Evaluation and Mitigation Strategy) program.7These programs function to notify the care provider of any significant drop in WBC/neutrophil count, or if there is a drop below a threshold level. Patients who enter the ""Red"" zone (WBC<2x109/L or ANC<1.5x109/L) should normally not be re-challenged.27Clozapine-induced myocarditis is a hypersensitivity reaction that usually occurs in the third week of clozapine therapy and about 2% of clozapine patients.5Monitor the patient's troponin, CRP, and ECG at baseline, and 28 days into treatment. Follow guidelines for appropriate next steps according to the patient's lab results. If myocarditis occurs, the patient should not be re-challenged with clozapine.27",CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12,"The mechanism of action of clozapine is unknown. However, it has been proposed that the therapeutic efficacy of clozapine in schizophrenia is mediated through antagonism of the dopamine type (D) and the serotonin type A (-HTA) receptors. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic, and other dopaminergic and serotonergic receptors.Clozapine demonstrated binding affinity to the following receptors: histamine H (Ki . nM), adrenergic αA (Ki . nM), serotonin -HT (Ki nM), serotonin -HTA (Ki . nM), muscarinic M (Ki . nM), serotonin -HT (Ki . nM), serotonin -HTC (Ki . nM), dopamine D (Ki nM), adrenergic αA (Ki nM), serotonin -HT (Ki nM), serotonin -HTA (Ki nM), dopamine D (Ki nM), dopamine D (Ki nM), dopamine D (Ki nM), and dopamine D (Ki nM).Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and HTwith similar receptor affinities may explain some of the other therapeutic and side effects of clozapine. Clozapine's antagonism of muscarinic M- receptors may explain its anticholinergic effects.Clozapine's antagonism of histamine H receptors may explain the somnolence observed with this drug.Clozapine's antagonism of adrenergic α receptors may explain the orthostatic hypotension observed with this drug.TargetActionsOrganismUDopamine D receptorantagonistHumansADopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorbinderHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor DantagonistHumansU-hydroxytryptamine receptor EantagonistHumansA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor antagonistHumansNAlpha-C adrenergic receptorantagonistHumansUHistamine H receptorantagonistHumansNHistamine H receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansNAlpha-B adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansNAlpha-B adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor Mpartial agonistHumansUMuscarinic acetylcholine receptor Mpartial agonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor Mpartial agonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUNeuron-specific vesicular protein calcyonunknownHumansUGlutathione S-transferase PNot AvailableHumansUGamma-aminobutyric acid type B receptor subunit positive modulatorHumansUGamma-aminobutyric acid type B receptor subunit positive modulatorHumansUGamma-aminobutyric acid receptor subunit alpha-antagonistHumansUGamma-aminobutyric acid receptor subunit beta-antagonistHumansUGamma-aminobutyric acid receptor subunit gamma-antagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diazepines, Oxazepines, Thiazepines and Oxepines', 'Dibenzazepines', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'OCT1 substrates', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT1D Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents', 'UGT1A4 substrates']" +DB00625,Efavirenz,Efavirenzis a non-nucleoside reverse transcriptase inhibitor used to treat HIV infection or prevent the spread of HIV.,['Q72547'],"Efavirenz (dideoxyinosine, ddI) is an oral non-nucleoside reverse transcriptase inhibitor (NNRTI). It is a synthetic purine derivative and, similar to zidovudine, zalcitabine, and stavudine. Efavirenz was originally approved specifically for the treatment of HIV infections in patients who failed therapy with zidovudine. Currently, the CDC recommends that Efavirenz be given as part of a three-drug regimen that includes another nucleoside reverse transcriptase inhibitor (e.g., lamivudine, stavudine, zidovudine) and a protease inhibitor or efavirenz when treating HIV infection.",FC(F)(F)[C@]1(OC(=O)NC2=C1C=C(Cl)C=C2)C#CC1CC1,"Similar to zidovudine, efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity of efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated efavirenz, this action may nevertheless account for some of the drug's toxicity.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ",[],"['Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'BSEP/ABCB11 Substrates', 'Central Nervous System Depressants', 'Cycloparaffins', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (moderate)', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (moderate)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor', 'Hydrocarbons, Acyclic', 'Inducers of Drug Clearance', 'Moderate Risk QTc-Prolonging Agents', 'Non-Nucleoside Reverse Transcriptase Inhibitors', 'Nonnucleoside Reverse Transcriptase Inhibitors', 'Nucleic Acid Synthesis Inhibitors', 'OCT1 inhibitors', 'Oxazines', 'QTc Prolonging Agents', 'Reverse Transcriptase Inhibitors', 'UGT1A1 Inducers']" +DB00914,Phenformin,"A biguanide hypoglycemic agent with actions and uses similar to those of metformin. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)","['Q13131', 'Q15842']","Used to treat diabetes, phenformin is a biguanide (contains 2 guanidino groups) hypoglycemic agent with actions and uses similar to those of metformin (Glucophage). Both drugs work by (1) decreasing the absorption of glucose by the intestines, (2) decreasing the production of glucose in the liver, and by (3) increasing the body's ability to use insulin more effectively. More specifically, phenformin improves glycemic control by improving insulin sensitivity. Phenformin is generally considered to be associated with an unacceptably high incidence of actic acidosis. In general biguanides should be used only in stable type II diabetics who are free of liver, kidney and cardiovascular problems and who cannot be controlled with diet.",NC(=N)NC(=N)NCCC1=CC=CC=C1,"Phenformin binds to the AMP-activated protein kinase (AMPK). AMPK is an ultra-sensitive cellular energy sensor that monitors energy consumption and down-regulates ATP-consuming processes when activated. The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK. Phenformin's hypoglycemic activity is related the effect it has in activating AMPK and fooling insulin sensitive cells into thinking that insulin levels are low and causing the body to use glucose as if in a state of low caloric consumption. This drug also seems to inhibit several varients of ATP-sensitive potassium channels (namely the receptor subtype Kir.).TargetActionsOrganismA'-AMP-activated protein kinase catalytic subunit alpha-activatorHumansUATP-sensitive inward rectifier potassium channel inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amidines', 'Biguanides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Guanidines', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'Oral Hypoglycemics']" +DB00709,Lamivudine,Lamivudineis a reverse transcriptase inhibitor used to treat HIV and hepatitis B infections.,"['Q72547', 'Q05486']","Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV) to disrupt viral DNA synthesis. When phosphorylated, lamivudine can form active metabolites that compete for incorporation into viral DNA. Via DNA incorporation, lamivudine metabolites competitively inhibit the activity of the HIV reverse transcriptase enzyme and act as a chain terminator of DNA synthesis. Due to the lack of a 3'-OH group, incorporated nucleoside analogues prevent the formation of a 5' to 3' phosphodiester linkage that is essential for DNA chain elongation.",NC1=NC(=O)N(C=C1)[C@@H]1CS[C@H](CO)O1,"Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active '-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ADNAbinderHumansAProtein PinhibitorHBV-F",[],"['Agents Causing Muscle Toxicity', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'BCRP/ABCG2 Substrates', 'Deoxycytidine', 'Deoxyribonucleosides', 'Dideoxynucleosides', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'OAT1/SLC22A6 Substrates', 'OCT1 substrates', 'OCT2 Substrates', 'P-glycoprotein substrates', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Reverse Transcriptase Inhibitors']" +DB00238,Nevirapine,Nevirapineis a non-nucleoside reverse transcriptase inhibitor used as part of a management regimen for HIV-1 virus infection.,['Q72547'],"Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time.",CC1=C2NC(=O)C3=C(N=CC=C3)N(C3CC3)C2=NC=C1,Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ,[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strong)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Hepatotoxic Agents', 'Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor', 'Inducers of Drug Clearance', 'Non-Nucleoside Reverse Transcriptase Inhibitors', 'Nonnucleoside Reverse Transcriptase Inhibitors', 'Nucleic Acid Synthesis Inhibitors', 'OCT1 inhibitors', 'Pyridines', 'Reverse Transcriptase Inhibitors']" +DB01035,Procainamide,Procainamideis a medication used to treat life threatening ventricular arrhythmias.,"['Q12809', 'Q14524', 'P26358']","Procainamide is an agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected.",CCN(CC)CCNC(=O)C1=CC=C(N)C=C1,Procainamide is sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.TargetActionsOrganismUPotassium voltage-gated channel subfamily H member inhibitorHumansUSodium channel protein type subunit alphainhibitorHumansUDNA (cytosine-)-methyltransferase otherHumans,[],"['Acids, Carbocyclic', 'Agents Causing Muscle Toxicity', 'Agents that produce neuromuscular block (indirect)', 'Amides', 'Aminobenzoates', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ia', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Highest Risk QTc-Prolonging Agents', 'MATE 1 Substrates', 'MATE 1 Substrates with a Narrow Therapeutic Index', 'MATE 2 Substrates', 'MATE 2 Substrates with a Narrow Therapeutic Index', 'MATE substrates', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'Negative Inotrope', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'OCT2 Substrates with a Narrow Therapeutic Index', 'para-Aminobenzoates', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB01099,Flucytosine,Flucytosineis an antifungal indicated only to treat severe infections throughout the body caused by susceptible strains of Candida or Cryptococcus.,"['P26358', 'P12461']","Flucytosine is an antimetabolite that acts as an antifungal agent within vitroandin vivoactivity against Candida and Cryptococcus. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. Antifungal synergism between Ancobon and polyene antibiotics, particularly amphotericin B, has been reported.",NC1=C(F)C=NC(=O)N1,"Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to -fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to -fluorouracil within fungal organisms. The -fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase.TargetActionsOrganismADNAcross-linking/alkylationHumansUDNA (cytosine-)-methyltransferase otherHumansUThymidylate synthaseinhibitorYeast",[],"['Anti-Infective Agents', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antimycotics for Systemic Use', 'Cytosine', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Fluorouracil and prodrugs', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Noxae', 'Nucleoside Analog Antifungal', 'Photosensitizing Agents', 'Pyrimidines', 'Pyrimidinones', 'Toxic Actions']" +DB00273,Topiramate,Topiramateis an anticonvulsant drug used in the control of epilepsy and in the prophylaxis and treatment of migraines.,"['P14867', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'P39086', 'Q13002', 'Q13003', 'Q16099', 'Q16478', 'P00918', 'P22748', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'P00915', 'P07451', 'Q15878']","Topiramate prevents the occurrence of seizures and prevents migraine symptoms by reducing neural pathway excitability.8,19It is important to note that this drug may cause metabolic acidosis, mood changes, suicidal thoughts and attempts, as well as kidney stones. When topiramate is combined withvalproic acid, it is known to cause hypothermia.19",[H][C@@]12CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@]3([H])[C@]1([H])OC(C)(C)O2,"A seizure is an abnormal and unregulated electrical discharge occurring in the brain. This leads to transient interruption in brain function, manifested by reduced alertness, abnormal sensations, and focal involuntary movements or convulsions. Several types of seizures exist, with common types including tonic-clonic seizures and partial onset seizures.The exact mechanisms by which topiramate exerts pharmacological actions on seizures and migraines are currently not fully characterized.,Several properties of this drug, however, are likely to contribute to its therapeutic effects. Topiramate has been observed to exert actions on voltage-dependent sodium channels, GABA receptors, and glutamate receptors.,Topiramate stimulates GABA-A receptor activity at brain non-benzodiazepine receptor sites and reduces glutamate activity at both AMPA and kainate receptors. Normally, GABA-A receptors are inhibitory and glutaminergic receptors are stimulatory for neuronal activity.,By increasing GABA activity and inhibiting glutamate activity, topiramate blocks neuronal excitability, preventing seizures and migraines.,,Additionally, it blocks the voltage-dependent sodium channels, further blocking seizure activity.Topiramate has been shown to inhibit various carbonic anhydrase isozymes, but the clinical significance of this is unknown at this time.,,,TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAVoltage-gated sodium channel alpha subunitinhibitorHumansAKainate receptorsantagonistHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansAVoltage gated L-type calcium channelantagonistHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUVoltage-dependent R-type calcium channelantagonistHumans","['Chronic Weight Management therapy', 'Weight Reduction']","['Alimentary Tract and Metabolism', 'Anti-Obesity Agents', 'Anticonvulsants', 'Antiobesity Preparations, Excl. Diet Products', 'Carbohydrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inducing Antiepileptic Drugs', 'Hexoses', 'Ketoses', 'Miscellaneous Anticonvulsants', 'Monosaccharides', 'Nervous System', 'Neuroprotective Agents', 'P-glycoprotein substrates']" +DB00421,Spironolactone,"Spironolactoneis an aldosterone receptor antagonist used to treat edema, hypertension, heart failure, and aldosteronism.","['P08235', 'P04150', 'P10275', 'P06401', 'P03372', 'Q92731', 'O75469', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555']","Spironolactone has a potassium-sparing diuretic effect. It promotes sodium and water excretion and potassium retention. It increases renin and aldosterone levels.7Spironolactone is a mineralocorticoid receptor antagonist and has a low affinity for the glucocorticoid receptor.13It also exhibits progestogenic and anti-androgenic actions as it binds to the androgen receptor and, to a lesser extent, estrogen and progesterone receptors.7,6,11Spironolactone exhibits anti-inflammatory effects.6",[H][C@@]12CC[C@@]3(CCC(=O)O3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@]([H])(CC2=CC(=O)CC[C@]12C)SC(C)=O,"Aldosterone is a key hormone in the renin-angiotensin-aldosterone system. By binding to the mineralocorticoid receptor at the distal tubules and collecting duct, it causes sodium reabsorption and potassium secretion, increases vascular stiffness and remodelling, and activates pro-inflammatory pathways.,Spironolactone and its active metabolites are aldosterone antagonists that produce a potassium-sparing diuretic effect. They competitively bind to receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents that act more proximally in the renal tubule.,TargetActionsOrganismAMineralocorticoid receptorantagonistHumansUGlucocorticoid receptorantagonistHumansUAndrogen receptorantagonistHumansUProgesterone receptoragonistHumansUEstrogen receptoragonistHumansUNuclear receptor subfamily group I member agonistHumansUVoltage-dependent L-type calcium channelinhibitorHumans","['Perioperative drug treatment', 'Maintenance therapy']","['Agents causing hyperkalemia', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Diuretics', 'Fused-Ring Compounds', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypotensive Agents', 'Lactones', 'Mineralocorticoid (Aldosterone) Receptor Antagonists', 'Mineralocorticoid Receptor Antagonists', 'Natriuretic Agents', 'P-glycoprotein inducers', 'Potassium-Sparing Diuretics', 'Pregnanes', 'Pregnenes', 'Steroids']" +DB01028,Methoxyflurane,"An inhalation anesthetic. Currently, methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with nitrous oxide to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation. (From AMA Drug Evaluations Annual, 1994, p180)","['P14867', 'P42261', 'P23415', 'Q09470', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P98194', 'P03886']",Methoxyflurane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.,COC(F)(F)C(Cl)Cl,"Methoxyflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Methoxyflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Methoxyflurane also binds to the GABA receptor, the large conductance Ca+activated potassium channel, the glutamate receptor and the glycine receptor.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGlutamate receptor antagonistHumansAGlycine receptor subunit alpha-agonistHumansAPotassium voltage-gated channel subfamily A member inducerHumansAGABA(A) Receptorpositive allosteric modulatorHumansUCalcium-transporting ATPase type C member inhibitorHumansUNADH-ubiquinone oxidoreductase chain unknownHumans",[],"['Agents that produce hypertension', 'Analgesics', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Inhalation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Ethers', 'Ethyl Ethers', 'Methyl Ethers', 'Miscellaneous Analgesics and Antipyretics', 'Nervous System']" +DB00369,Cidofovir,Cidofoviris an antiviral agent used to treat Cytomegalovirus (CMV) retinitis in patients with AIDS.,['P08546'],Cidofovir is a new anti-viral drug. It is classified as a nucleotide analogue and is active against herpes cytomegalovirus (CMV) retinitis infection. Most adults are infected with CMV. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis.,NC1=NC(=O)N(C[C@@H](CO)OCP(O)(O)=O)C=C1,"Cidofovir acts through the selective inhibition of viral DNA polymerase.Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Cidofovir diphosphate inhibits herpesvirus polymerases at concentrations that are - to -fold lower than those needed to inhibit human cellular DNA polymerase alpha, beta, and gamma(,,). Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytomegalovirus Nucleoside Analog DNA Polymerase Inhibitor', 'Cytosine', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Nephrotoxic agents', 'Nucleic Acid Synthesis Inhibitors', 'Nucleosides and Nucleotides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'Organophosphonates', 'Organophosphorus Compounds', 'Pyrimidines', 'Pyrimidinones']" +DB08804,Nandrolone decanoate,Nandrolone decanoateis an anabolic steroid indicated for the management of the anemia of renal insufficiency by increasing hemoglobin and red cell mass.,"['P10275', 'P01100', 'P28223', 'P41595', 'P28335', 'P28222', 'P08069', 'P21728', 'P21918', 'P14416', 'P35462', 'P21917']","Nandrolone decanoate is an alkylated anabolic steroid indicated in the management of anemia of renal insufficiency and as an adjunct therapy in the treatment of senile and postmenopausal osteoporosis.8,12,13It has a long duration of action as it is given every 3-4 weeks, and a wide therapeutic window as acute overdoses are rare.8,13Patients should be counselled regarding the risks of giving this drug to patients with cardiac, renal, or hepatic diseases.13",[H][C@@]12CC[C@H](OC(=O)CCCCCCCCC)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H],"Nandrolone decanoate is hydrolyzed tonandrolone, possibly by PDEB.,Nandrolone is brought into cells by receptor mediated endocytosis, where it interacts with the androgen receptor.,After binding to the androgen receptor, a conformational change occurs, the androgen receptor enters the nucleus, dimerizes, and can then bind to segments of DNA to regulate transcription.Androgens can also regulate transcription through activation of ERK, Akt, and MAPK; or binding to and competitively inhibiting transcription factors.TargetActionsOrganismAAndrogen receptoragonistHumansUProto-oncogene c-FosinducerHumansU-hydroxytryptamine receptormodulatorHumansU-hydroxytryptamine receptor BmodulatorHumansUInsulin-like growth factor receptorinducerHumansUDopamine receptormodulatorHumans",[],"['Anabolic Agents', 'Androgens', 'Bone Density Conservation Agents', 'Estranes', 'Estrenes', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nandrolone and esters', 'Steroids', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A4 substrates', 'UGT2B7 substrates']" +DB06718,Stanozolol,Stanozololis an anabolic steroid used to manage hereditary angioedema.,['P10275'],"Stanozolol is a synthetic anabolic-androgenic steroid (AAS), which promotes cell growth (anabolism) and development/maintenance of masculine characteristics (androgenism).",[H][C@@]12CC[C@](C)(O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])CC3=NNC=C3C[C@]12C,"Stanozolol binds to androgen receptors, such as membrane bound receptor proteins LAGS and stanozolol-binding protein (STBP).TargetActionsOrganismAAndrogen receptoragonistHumansUGlucocorticoid binding proteinsbinderHumans",[],"['Alimentary Tract and Metabolism', 'Anabolic Agents', 'Anabolic Agents for Systemic Use', 'Anabolic Steroids', 'Androgens', 'Androstan Derivatives', 'Androstanes', 'Androstanols', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Steroids', 'Thyroxine-binding globulin inhibitors']" +DB01183,Naloxone,Naloxoneis an opioid receptor antagonist used to rapidly reverse an opioid overdose. Also included in some drug formulations as an abuse deterrent to prevent injection.,"['P35372', 'P41143', 'P41145', 'P16220', 'P03372', 'O00206', 'P23141']","Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses.7Naloxone has a shorter duration of action than opioids and multiple doses may be required.3,7The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids.4,7Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved.7",OC1=CC=C2C[C@H]3N(CC=C)CC[C@@]45[C@@H](OC1=C24)C(=O)CC[C@@]35O,"Naloxone is a competitive inhibitor of the µ-opioid receptor.,Naloxone antagonizes the action of opioids, reversing their effects.If a patient has not taken opioids, naloxone does not have a significant effect on patients.TargetActionsOrganismAMu-type opioid receptorantagonistHumansADelta-type opioid receptorantagonistHumansAKappa-type opioid receptorantagonistHumansNCyclic AMP-responsive element-binding protein other/unknownHumansNEstrogen receptor alphaantagonistother/unknownHumansUToll-like receptor inhibitorHumansULiver carboxylesterase binderHumans",['Emergency Care'],"['Alimentary Tract and Metabolism', 'Alkaloids', 'Analgesics', 'Antidotes', 'Central Nervous System Agents', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Constipation', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Natural Opium Alkaloids', 'Nervous System', 'Opiate Alkaloids', 'Opiate Antagonists', 'Opioid Antagonists', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Peripheral Opioid Receptor Antagonists', 'Phenanthrenes', 'Sensory System Agents', 'UGT1A1 Substrates']" +DB00652,Pentazocine,Pentazocineis an analgesic used to treat moderate to severe pain.,"['Q99720', 'P35372', 'P41145']","Pentazocine is a potent analgesic which when administered orally in a 50 mg dose appears equivalent in analgesic effect to 60 mg (1 grain) of codeine. Onset of significant analgesia usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine and meperidine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has sedative activity.",CC1C2CC3=C(C=C(O)C=C3)C1(C)CCN2CC=C(C)C,"The preponderance of evidence suggests that pentazocine antagonizes the opioid effects by competing for the same receptor sites, especially the opioid mu receptor.TargetActionsOrganismASigma non-opioid intracellular receptor agonistHumansAMu-type opioid receptorantagonistHumansAKappa-type opioid receptoragonistHumans",['Anesthetic premedication therapy'],"['Adjuvants, Anesthesia', 'Agents that reduce seizure threshold', 'Alkaloids', 'Analgesics', 'Benzomorphan Derivatives', 'Benzomorphans', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Mixed Agonist / Antagonist Opioids', 'Morphinans', 'Narcotics', 'Nervous System', 'Opiate Alkaloids', 'Opiate Partial Agonists', 'Opioid Antagonists', 'Opioids', 'P-glycoprotein substrates', 'Partial Opioid Agonist/Antagonist', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB01541,Boldenone,"Boldenone is an anabolic steroid developed for veterinary use, mostly for treatment of horses. It is not indicated for use in humans in the US and is only available through veterinary clinics.",['P10275'],"Boldenone has primarily anabolic activity with low androgenic potency. The drug is commonly used in doping within bodybuilding, even though this use is illegal. If intended to assist in bodybuilding, the drug is taken as part of a steroid stack of other anabolic steroids, usually with a potent androgen like testosterone as the 'base' of the stack. Boldenone is an androgen that differs from 17b-testosterone (17b-T) by only one double bond at the 1-position, and the removal of the methyl group protecting the 17-OH group allows it to be orally active.",[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Boldenone is a steroid hormone which has androgenic activity. Androgens bind to the androgen receptor, which regulates gene transcription.TargetActionsOrganismAAndrogen receptoragonistHumans",[],"['Anabolic Agents', 'Androstanes', 'Androstenes', 'Androstenols', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Steroids', 'Testosterone and derivatives', 'Testosterone Congeners']" +DB00802,Alfentanil,"Alfentanilis an opioid agonist used to induce and maintain anesthesia, as well as an analgesic.",['P35372'],"Alfentanil is a synthetic opioid analgesic. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.",CCN1N=NN(CCN2CCC(COC)(CC2)N(C(=O)CC)C2=CC=CC=C2)C1=O,"Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Alfentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP and OP receptor agonist). This results in hyperpolarization and reduced neuronal excitability.TargetActionsOrganismAMu-type opioid receptoragonistHumans","['General Anesthesia', 'Induction of anesthesia therapy', 'Maintenance of anesthesia therapy', 'Monitored anesthesia care sedation', 'Perioperative analgesia']","['Agents that produce hypertension', 'Analgesics', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Bradycardia-Causing Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Fentanyl and fentanyl analogues', 'High-risk opioids', 'Narcotics', 'Nervous System', 'Opiate Agonists', 'Opioid Agonist', 'Opioid Anesthetics', 'Opioids', 'Opioids, Anilidopiperidine', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Phenylpiperidine opioids', 'Piperidines', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00813,Fentanyl,"Fentanylis an opioid analgesic used in anesthesia, for breakthrough cancer pain, or round the clock pain management.","['P35372', 'P41143', 'P41145', 'P08183']","Fentanyl produces strong analgesia through its activation of opioid receptors.Label,6It has a duration of action of several hours and a wider therapeutic index as patients develop tolerance to opioids.LabelFentanyl is associated with a risk of addiction and abuse and should not be mixed with alcohol or benzodiazepines.Label,15,16,17,18,19,20,21",CCC(=O)N(C1CCN(CCC2=CC=CC=C2)CC1)C1=CC=CC=C1,"Fentanyl binds to opioid receptors, especially the mu opioid receptor, which are coupled to G-proteins.Activation of opioid receptors causes GTP to be exchanged for GDP on the G-proteins which in turn down regulates adenylate cyclase, reducing concentrations of cAMP.Reduced cAMP decreases cAMP dependant influx of calcium ions into the cell.The exchange of GTP for GDP results in hyperpolarization of the cell and inhibition of nerve activity.TargetActionsOrganismAMu-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumansUP-glycoprotein Not AvailableHumans","['Anesthetic premedication therapy', 'Anesthetics Agent', 'General Anesthesia', 'Induction of anesthesia therapy', 'Maintenance of anesthesia therapy', 'Regional Anesthesia therapy']","['Adjuvants', 'Adjuvants, Anesthesia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Analgesics', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Antidepressive Agents', 'Bradycardia-Causing Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fentanyl and fentanyl analogues', 'High-risk opioids', 'Narcotics', 'Nervous System', 'Neuraxial Anesthetics', 'Opiate Agonists', 'Opioid Agonist', 'Opioid Anesthetics', 'Opioids', 'Opioids, Anilidopiperidine', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Phenylpiperidine opioids', 'Piperidines', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB00319,Piperacillin,"Piperacillinis a penicillin antibiotic combined with tazobactam to treat piperacillin-resistant, piperacillin/tazobactam­ susceptible, β-lactamase generating strains of several bacteria.","['Q75Y35', 'P0A3M6', 'Q8DNB6', 'Q7CRA4']","Piperacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name ""penicillin"" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Piperacillin hasin vitroactivity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Piperacillin results from the inhibition of cell wall synthesis and is mediated through Piperacillin binding to penicillin binding proteins (PBPs). Piperacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=CC=C1)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, Piperacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Piperacillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Agents that produce neuromuscular block (indirect)', 'Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Drugs that are Mainly Renally Excreted', 'Extended-spectrum Penicillins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Substrates', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00294,Etonogestrel,Etonogestrelis a long-acting synthetic derived progestin contraceptive used in various devices such as contraceptive rings and intradermal implants.,['P06401'],"Etonogestrel attains its therapeutic effect inhibiting fertility by impairing the release of the luteinizing hormone which is one of the most important reproductive hormones for ovulation. As well, etonogestrel is known to increase the viscosity of the cervical mucus hindering the passage of the spermatozoa and altering the lining in the uterus to prevent the implantation of the fertilized eggs in the endometrium.7In clinical trials, etonogestrel was implanted and reported to avoid 100% of pregnancies over a three year period. When the implant was removed, normal periods were reinstalled within 90 days in 91% of the individuals. Fertility was established quickly with 20 reported pregnancies within 3 months of implant removal.7The implants of etonogestrel release 40 mcg of etonogestrel daily and they usually provide a continuous contraception effect for 3 years. When the implant is administered, the failure rate is reported to be 0.1%. Some non-contraceptive effects are improved dysmenorrhea.4All data of etonogestrel comes from patients between 80-130% of the body mass.",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC(=C)[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H],"Etonogestrel binds with high affinity to the progesterone and estrogen receptors in the target organs.From the target organs, they include the female reproductive tract, mammary gland, hypothalamus, and pituitary. Once bound, this drug changes the synthesis of different proteins which in order decreases the level of gonadotropin-releasing hormone and the luteinizing hormone.TargetActionsOrganismAProgesterone receptoragonistHumans","['Contraception', 'Contraceptive implant therapy']","['Adrenal Cortex Hormones', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hyperglycemia-Associated Agents', 'Intravaginal Contraceptives', 'Norpregnanes', 'Norpregnenes', 'Norsteroids', 'Progesterone Congeners', 'Progestins', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00744,Zileuton,Zileutonis a leukotriene synthesis inhibitor used in the prophylaxis and treatment of chronic asthma.,['P09917'],"Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.",CC(N(O)C(N)=O)C1=CC2=CC=CC=C2S1,"Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of -lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB, LTC, LTD, and LTE formation. Both the R(+) and S(-) enantiomers are pharmacologically active as -lipoxygenase inhibitors inin vitrosystems. Due to the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of -lipoxygenase activity may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control.TargetActionsOrganismAArachidonate -lipoxygenaseinhibitorHumans",[],"['Agents to Treat Airway Disease', 'Amides', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Leukotriene Production', 'Enzyme Inhibitors', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Leukotriene Antagonists', 'Lipoxygenase Inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'UGT1A9 Substrates']" +DB00210,Adapalene,"Adapaleneis a third-generation topical retinoid with anti-comedogenic, comedolytic, and anti-inflammatory properties used to treat acne vulgaris in adolescents and adults.","['P10826', 'P13631', 'P28702', 'P48443', 'P19793', 'P05412', 'O60603', 'P10276', 'P17174']","Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response.2Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.8",COC1=C(C=C(C=C1)C1=CC2=C(C=C1)C=C(C=C2)C(O)=O)C12CC3CC(CC(C3)C1)C2,"Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity.Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation.These effects primarily account for adapalene's comedolytic and anticomedogenic properties.In addition, adapalene modulates the immune response by down-regulating toll-like receptor (TLR-) expression and inhibiting the transcription factor activator protein (AP-). TLR- recognizesCutibacterium acnes(formerlyPropionibacterium acnes), the bacterium primarily associated with acne. TLR- activation causes nuclear translocation of AP- and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms.When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.TargetActionsOrganismARetinoic acid receptor betaagonistHumansARetinoic acid receptor gammaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor RXR-gammaagonistHumansARetinoic acid receptor RXR-alphaagonistHumansATranscription factor AP-antagonistHumansAToll-like receptor antagonistHumansURetinoic acid receptor alphaNot AvailableHumansUAspartate aminotransferase, cytoplasmicinhibitorHumans",[],"['Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Inflammatory Agents', 'Dermatologicals', 'Misc. Skin and Mucous Membrane Agents', 'Naphthalenes', 'Retinoids', 'Retinoids for Topical Use in Acne']" +DB04839,Cyproterone acetate,Cyproterone acetateis a steroid used in combination with ethinyl estradiol to treat women with severe acne and symptoms of androgenization. Also used alone at much higher doses for palliative treatment of patients with prostate cancer,"['P10275', 'P07288']",Cyproterone is an antiandrogen. It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels).,[H][C@@]12C[C@]1([H])[C@@]1(C)C(=CC2=O)C(Cl)=C[C@@]2([H])[C@]3([H])CC[C@](OC(C)=O)(C(C)=O)[C@@]3(C)CC[C@]12[H],"The direct antiandrogenic effect of cyproterone is blockage of the binding of dihydrotestosterone to the specific receptors in the prostatic carcinoma cell. In addition, cyproterone exerts a negative feed-back on the hypothalamo-pituitary axis, by inhibiting the secretion of luteinizing hormone resulting in diminished production of testicular testosterone.TargetActionsOrganismAAndrogen receptorantagonistHumansUProstate-specific antigenNot AvailableHumans",['Hormone Replacement Therapy'],"['Adrenal Cortex Hormones', 'Antiandrogens', 'Antiandrogens and Estrogens', 'Antineoplastic Agents', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Male', 'Contraceptives, Oral', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Other Miscellaneous Therapeutic Agents', 'Pregnadienes', 'Pregnanes', 'Progestin Contraceptives', 'Progestins', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Steroids, Chlorinated']" +DB01190,Clindamycin,"Clindamycinis a lincosamide antibiotic used to treat serious infections caused by susceptible anaerobic, streptococcal, staphylococcal, and pneumococcal bacteria.",['Q2G0P0'],"Clindamycin exerts its bacteriostatic effect via inhibition of microbial protein synthesis.8Clindamycin has a relatively short Tmaxand half-life necessitating administration every six hours to ensure adequate antibiotic concentrations.20Clostridium difficileassociated diarrhea (CDAD) has been observed in patients using clindamycin, ranging in severity from mild diarrhea to fatal colitis and occasionally occurring over two months following cessation of antibiotic therapy.15Overgrowth ofC. difficileresulting from antibiotic use, along with its production of A and B toxins, contributes to morbidity and mortality in these patients. Because of the associated risks, clindamycin should be reserved for serious infections for which the use of less toxic antimicrobial agents are inappropriate.15Clindamycin is active against a number of gram-positive aerobic bacteria, as well as both gram-positive and gram-negative anaerobes.14Resistance to clindamycin may develop, and is generally the result of base modification within the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete, and may also occur between clindamycin and macrolide antibiotics (e.g.erythromycin) due to similarities in their binding sites.14As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.",[H][C@@](NC(=O)[C@@H]1C[C@@H](CCC)CN1C)([C@H](C)Cl)[C@@]1([H])O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O,"Clindamycin inhibits bacterial protein synthesis by binding to S RNA of the S subunit of the bacterial ribosome.It impedes both the assembly of the ribosome and the translation process.The molecular mechanism through which this occurs is thought to be due to clindamycin's three-dimensional structure, which closely resembles the '-ends of L-Pro-Met-tRNA and deacylated-tRNA during the peptide elongation cycle - in acting as a structural analog of these tRNA molecules, clindamycin impairs peptide chain initiation and may stimulate dissociation of peptidyl-tRNA from bacterial ribosomes.The mechanism through which topical clindamycin treats acne vulgaris is unclear, but may be related to its activity againstPropionibacterium acnes, a bacteria that has been associated with acne.TargetActionsOrganismAS ribosomal protein LinhibitorStaphylococcus aureus (strain NCTC )",[],"['Agents that produce neuromuscular block (indirect)', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Pneumocystis Pneumonia', 'Antiinfectives for Systemic Use', 'Antiinfectives for Treatment of Acne', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Sebaceous Gland Activity', 'Dermatologicals', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Glycosides', 'Gynecological Antiinfectives and Antiseptics', 'Lincomycins', 'Lincosamide Antibacterial', 'Lincosamides', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'Neuromuscular Blockade', 'Neurotoxic agents', 'P-glycoprotein substrates', 'Protein Synthesis Inhibitors', 'Pyrrolidines']" +DB00548,Azelaic acid,Azelaic acidis a saturated dicarboxylic acid used to treat mild to moderate acne vulgaris.,"['P66010', 'P51857', 'P31213', 'P14679', 'P00582']","Azelaic acid is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. It is a natural substance that is produced byMalassezia furfur(also known asPityrosporum ovale), a yeast that lives on normal skin. It is effective against a number of skin conditions, such as mild to moderate acne, when applied topically in a cream formulation of 20%. It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores clear. Azelaic acid's antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.",OC(=O)CCCCCCCC(O)=O,"The exact mechanism of action of azelaic acid is not known. It is thought that azelaic acid manifests its antibacterial effects by inhibiting the synthesis of cellular protein in anaerobic and aerobic bacteria, especiallyStaphylococcus epidermidisandPropionibacterium acnes. In aerobic bacteria, azelaic acid reversibly inhibits several oxidoreductive enzymes including tyrosinase, mitochondrial enzymes of the respiratory chain, thioredoxin reductase, -alpha-reductase, and DNA polymerases. In anaerobic bacteria, azelaic acid impedes glycolysis. Along with these actions, azelaic acid also improves acne vulgaris by normalizing the keratin process and decreasing microcomedo formation. Azelaic acid may be effective against both inflamed and noninflamed lesions. Specifically, azelaic acid reduces the thickness of the stratum corneum, shrinks keratohyalin granules by reducing the amount and distribution of filaggrin (a component of keratohyalin) in epidermal layers, and lowers the number of keratohyalin granules.TargetActionsOrganismAThioredoxin reductaseinhibitorStaphylococcus aureus (strain Mu / ATCC )A-oxo--beta-steroid -dehydrogenaseinhibitorHumansA-oxo--alpha-steroid -dehydrogenase inhibitorHumansATyrosinaseinhibitorHumansADNA polymerase IinhibitorEscherichia coli (strain K)",['Nutritional supplementation'],"['Acids, Acyclic', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Decreased Protein Synthesis', 'Decreased Sebaceous Gland Activity', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Misc. Skin and Mucous Membrane Agents']" +DB00250,Dapsone,"Dapsoneis a sulfone drug used to treat acne vulgaris, Hansen's disease, and dermatitis herpetiformis.","['P0C0X2', 'P0C0X1']","Dapsone is a sulfone with anti-inflammatory immunosuppressive properties as well as antibacterial and antibiotic properties. Dapsone is the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. As an anti-infective agent, it is also used for treating malaria and, recently, for Pneumocystic carinii pneumonia in AIDS patients. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Dapsone is distributed throughout total body water and is present in all tissues. However, it tends to be retained in skin and muscle and especially in the liver and kidney: traces of the drug are present in these organs up to 3 weeks after therapy cessation.",NC1=CC=C(C=C1)S(=O)(=O)C1=CC=C(N)C=C1,"Dapsone acts against bacteria and protozoa in the same way as sulphonamides, that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood.TargetActionsOrganismAInactive dihydropteroate synthase inhibitorMycobacterium leprae (strain TN)ADihydropteroate synthase inhibitorMycobacterium leprae (strain TN)",[],"['Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics for Pneumocystis Pneumonia', 'Antiinfectives for Systemic Use', 'Antimalarials', 'Antimycobacterials', 'Antiparasitic Agents', 'Antiprotozoals', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Drugs for Treatment of Lepra', 'Enzyme Inhibitors', 'Folic Acid Antagonists', 'Leprostatic Agents', 'Methemoglobinemia Associated Agents', 'Miscellaneous Antimycobacterials', 'Miscellaneous Local Anti-infectives', 'Photosensitizing Agents', 'Sulfones', 'Sulfur Compounds']" +DB04836,Amineptine,"The Food and Drug Administration suspended the marketing authorisation for Survector in 1999 and France withdrew it from the market, however several developing countries continued to produce it up until 2005.","['P23975', 'P31645']",Amineptine is an atypical tricyclic antidepressant.,OC(=O)CCCCCCNC1C2=CC=CC=C2CCC2=CC=CC=C12,"Amineptine selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect.TargetActionsOrganismUSodium-dependent noradrenaline transporterNot AvailableHumansUSodium-dependent serotonin transporterNot AvailableHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antidepressive Agents, Tricyclic', 'Benzocycloheptenes', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Non-Selective Monoamine Reuptake Inhibitors', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB09123,Dienogest,Dienogestis an oral progestin used for the treatment of endometriosis as monotherapy or contraception in combination with ethinylestradiol.,"['P06401', 'P10275']","Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use2. It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate5. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. 1mg/kg of dienogest also directly inhibits ovulation2. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder1. +Dienogest displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ4, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα3. It has no glucocorticoid or mineralocorticoid effects. In combined oral contraceptive pills (COCP) with ethinyloestradiol, dienogest conjuction therapy effectively reduces the symptoms of acne and hirsutism, as well as improving excessively heavy or prolonged menstrual bleeding2.",[H][C@@]12CC[C@@](O)(CC#N)[C@@]1(C)CCC1=C3CCC(=O)C=C3CC[C@@]21[H],"Dienogest acts as an agonist at the progesterone receptor (PR) with weak affinity that is comparable to that of progesterone but has a very potent progestagenic effect in the endometrium, causing endometrial atrophy after prolonged use. It promotes antiproliferative, immunologic and antiangiogenic effects on endometrial tissue. Dienogest reduces the level of endogenous production of oestradiol and thereby suppressing the trophic effects of oestradiol on both the eutopic and ectopic endometrium. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue. +It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism.TargetActionsOrganismAProgesterone receptoragonistHumansAAndrogen receptorantagonistHumans","['Contraception', 'Oral Contraceptives']","['Adrenal Cortex Hormones', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptive Agents, Male', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Estranes', 'Estrenes', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormone Antagonists', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Pregnadien Derivatives', 'Progestin Contraceptives', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Testosterone Congeners']" +DB00595,Oxytetracycline,Oxytetracyclineis a tetracycline antibiotic used to treat a wide variety of susceptible bacterial infections.,"['P0A7X3', 'P0A7V8']","Oxytetracycline is known as a broad-spectrum antibiotic due to its activity against such a wide range of infections. It was the second of the tetracyclines to be discovered. Oxytetracycline, like other tetracyclines, is used to treat many infections common and rare. Its better absorption profile makes it preferable to tetracycline for moderately severe acne, but alternatives sould be sought if no improvement occurs by 3 months.",[H][C@@]12[C@@H](O)[C@@]3([H])C(C(=O)C4=C(C=CC=C4O)[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C,Oxytetracycline inhibits cell growth by inhibiting translation. It binds to the S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Oxytetracycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)US ribosomal RNAinhibitorEnteric bacteria and other eubacteria,[],"['Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Antiinfectives for Systemic Use', 'Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Naphthacenes', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Ophthalmologicals', 'Sensory Organs', 'Stomatological Preparations', 'Tetracyclines']" +DB00199,Erythromycin,Erythromycinis a macrolide antibiotic used to treat and prevent a variety of bacterial infections.,"['O43193', 'Q12809']","Macrolides, such as erythromycin, stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections.8Erythromycin does not exert effects on nucleic acid synthesis.21This drug has been shown to be active against most strains of the following microorganisms, effectively treating both in vitro and clinical infections. Despite this, it is important to perform bacterial susceptibility testing before administering this antibiotic, as resistance is a common issue that may affect treatment.21A note on antimicrobial resistance, pseudomembranous colitis, and hepatotoxicityMany strains of Haemophilus influenzae are resistant to erythromycin alone but are found to be susceptible to erythromycin and sulfonamides used in combination. It is important to note that Staphylococci that are resistant to erythromycin may emerge during erythromycin and/or sulfonamide therapy.21Pseudomembranous colitis has been reported with most antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, the physician should consider this diagnosis in patients with diarrhea after the administration of antibacterial agents.21Erythromycin can cause hepatic dysfunction, cholestatic jaundice, and abnormal liver transaminases, particularly when erythromycin estolate is administered.22",CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O,"In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins.Erythromycin acts by inhibition of protein synthesis by binding to the S ribosomal RNA molecule in the S subunit of ribosomes in susceptible bacterial organisms. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the S ribosomal subunit.,This results in the control of various bacterial infections.,The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities.TargetActionsOrganismAS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaNMotilin receptoragonistHumansNPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Antiinfectives for Treatment of Acne', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Erythromycin and similars', 'Erythromycins', 'Gastrointestinal Agents', 'Lactones', 'Macrolide Antimicrobial', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'Moderate Risk QTc-Prolonging Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 inhibitors', 'OATP1B3 substrates', 'Ophthalmologicals', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protein Synthesis Inhibitors', 'QTc Prolonging Agents']" +DB00367,Levonorgestrel,Levonorgestrelis a progestin found in oral and IUD contraceptives and at higher doses in emergency contraceptives.,"['P06401', 'P18405', 'P03372', 'P10275', 'P04278', 'P04150']","Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse.3,7The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy.14,21,22Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration.13",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H],"Mechanism of action on ovulationOral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation.Mechanism of action in cervical mucus changesSimilar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted.,Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred.Interestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus.The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation.,Effects on implantation*The effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious.,Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity.,Mechanism of action in hormone therapyWhen combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use.TargetActionsOrganismAProgesterone receptormodulatorHumansA-oxo--alpha-steroid -dehydrogenase inhibitorHumansAEstrogen receptor alphaother/unknownHumansUAndrogen receptorbinderHumansUSex hormone-binding globulininhibitorbinderHumansUGlucocorticoid receptorbinderHumans",['Emergency Contraception'],"['Adrenal Cortex Hormones', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Synthetic', 'Contraceptives, Postcoital', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hyperglycemia-Associated Agents', 'Inhibit Ovum Fertilization', 'Norpregnanes', 'Norpregnenes', 'Norsteroids', 'Progestin Contraceptives', 'Progestin-containing Intrauterine Device', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB09096,Benzoyl peroxide,Benzoyl peroxideis an antibacterial and anti-inflammatory agent used for the symptomatic treatment of mild to moderate acne vulgaris and rosacea.,"['P04040', 'O75715', 'P07203', 'P18283', 'P22352', 'P59796', 'Q96SL4', 'P36969', 'Q8TED1', 'Q96A70', 'P17252', 'P05771', 'Q05655', 'Q02156', 'P05129', 'P41743', 'Q04759', 'Q05513', 'P08294', 'P00441', 'P04179']","Benzoyl peroxide is a topical treatment for acne that generates free radicals to break down comedones and increase the rate of epithelial cell turnover.1,3,4,5,9,10,11,12It has a short duration of action as its active free radical metabolites quickly react to form inactive metabolites.1The therapeutic index is wide, as overdoses are rare, however patients may still experience skin peeling.9,10,11,12Patients should be counselled regarding increased risks of skin irritation, dryness, and sunburn.9,10,11,12",O=C(OOC(=O)C1=CC=CC=C1)C1=CC=CC=C1,"Acne vulgaris is caused by inflammation in the pilosebaceous gland.Acne is generally caused by increased excretion of sebum from pilosebaceous glands, endocrine factors such as androgenic hormones, keratin developing around follicles, bacterial growth, and inflammation.These factors contribute to the formation of comedones (whiteheads and blackheads).The peroxide bond of benzoyl peroxide is cleaved to form benzoyloxy radicals.These radicals interact nonspecifically with bacterial proteins, interfering with their function, and survival of the bacteria.Over time, free radical interactions with bacterial proteins lead to decreased keratin and sebum around follicles.,Benzoyl peroxide can also increase the turnover rate of epithelial cells, leading to skin peeling, and breaking down comedones.TargetActionsOrganismUCatalaseinhibitorHumansUGlutathione peroxidaseinhibitorUArginine decarboxylaseactivatorHumansUProtein kinase CinhibitorHumansUSuperoxide DismutasesinhibitorHumans",[],"['Acids, Carbocyclic', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Benzene Derivatives', 'Benzoates', 'Dermatologicals', 'Keratolytic Agents', 'Peroxides']" +DB00957,Norgestimate,Norgestimateis a progesterone used as a contraceptive and to treat acne vulgaris.,"['P06401', 'P03372', 'P10275']","Norgestimate is a progestin that suppresses ovulation for contraception and reduces free testosterone to treat moderate acne vulgaris.7,10,11The therapeutic index is wide as overdoses are rare.10,11Patients should be counselled regarding the risk of vascular problems, liver disease, hypertension, metabolic effects, headaches, and bleeding irregularities.10,11",[H][C@@]12CC[C@@](OC(C)=O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CC\C(C=C3CC[C@@]21[H])=N/O,"Progesterone analogs like norgestimate decrease the frequency of gonadotropin releasing hormone pulses from the hypothalamus, decreasing follicle stimulating hormone and luteinizing hormone.These actions prevent ovulation.,Norgestimate suppresses the hypothalamo-pituitary-axis, reducing androgen synthesis.It also induces production of sex hormone binding globulin, which decreases free testosterone.These actions together result in less testosterone being available to stimulate sebaceous glands, resulting in effective treatment of some forms of acne.TargetActionsOrganismAProgesterone receptoragonistHumansAEstrogen receptor alphaagonistHumansUAndrogen receptorpartial agonistHumans",['Oral Contraceptives'],"['Adrenal Cortex Hormones', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Synthetic', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hyperglycemia-Associated Agents', 'Norpregnanes', 'Norpregnenes', 'Norsteroids', 'P-glycoprotein inhibitors', 'Progestin Contraceptives', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'UGT1A1 Substrates']" +DB01082,Streptomycin,Streptomycinis an aminoglycoside antibiotic indicated to treat multi-drug resistant mycobacterium tuberculosis and various non-tuberculosis infections.,"['P0A7S3', 'Q9UM07']","Although streptomycin originally had broad gram-negative and gram-positive coverage, its spectrum of activity has been significantly narrowed due to antibiotic resistance.2Streptomycins current spectrum of activity includes susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis, H. ducreyi, H. influenza, K. pneumoniae pneumonia, E.coli, Proteus, A. aerogenes, K. pneumoniae, Enterococcus faecalis, Streptococcus viridans, Enterococcus faecalis, and Gram-negative bacillary bacteremia. Streptomycin is not reliably active against pseudomonas aeruginosa.2Similar to other aminoglycosides, streptomycin is considered to have a narrow therapeutic index.18Characteristic toxicities of streptomycin include nephrotoxicity and ototoxicity.2,6Patients should be carefully monitored for early signs of hearing loss and vestibular dysfunction in order to prevent permanent damage to sensorineural cells. Neuromuscular blockade has also been rarely reported.6",CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](NC(N)=N)[C@@H](O)[C@@H]2NC(N)=N)O[C@@H](C)[C@]1(O)C=O,"There are key phases of aminoglycoside entry into cells.The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry.,,,The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial S ribosome.,This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane.Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified.,,Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model.,Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the S rRNA in helix (h), near the A site of the S ribosomal subunit, altering interactions between h and h. This binding also displaces two important residues, A and A, from h, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site.,Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling.,,Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h of the S rRNA of the S ribosomal subunit.,Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation.Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.,TargetActionsOrganismAS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaAS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaAS ribosomal protein SinhibitorEscherichia coli (strain K)ACytoplasmic membraneincorporation into and destabilizationBacteriaABacterial outer membraneincorporation into and destabilizationBacteriaNProtein-arginine deiminase type-inhibitorHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Glycosides', 'Intestinal Antiinfectives', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'Protein Synthesis Inhibitors', 'Streptomycins']" +DB00540,Nortriptyline,Nortriptylineis a tricyclic antidepressant used in the treatment of depression.,"['P23975', 'P31645', 'P28223', 'P08908', 'P35367', 'P35348', 'P25100', 'P28335', 'P35368', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945', 'P14416', 'O00264', 'Q99720', 'P08909', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Nortriptyline exerts antidepressant effects likely by inhibiting the reuptake of serotonin and norepinephrine at neuronal cell membranes. It also exerts antimuscarinic effects through its actions on the acetylcholine receptor.18,19",CNCCC=C1C2=CC=CC=C2CCC2=CC=CC=C12,"Though prescribing information does not identify a specific mechanism of action for nortriptyline, is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at the level of the beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain increased symptom improvement after nortriptyline therapy.Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.As with other tricyclics, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors, -HT receptors, in addition to other receptors.,,TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor AantagonistHumansNHistamine H receptorantagonistHumansNAlpha-A adrenergic receptorantagonistHumansNAlpha-D adrenergic receptorantagonistHumansU-hydroxytryptamine receptor CantagonistdownregulatorHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha- adrenergic receptorsantagonistHumansUBeta adrenergic receptorantagonistHumansUDopamine D receptorantagonistHumansUSigma receptorbinderHumansU-hydroxytryptamine receptor CantagonistRatUMuscarinic acetylcholine receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Benzocycloheptenes', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dibenzocycloheptenes', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB01113,Papaverine,"Papaverineis an alkaloid used to treat many types of smooth muscle spasms such as ""vascular spasms"" associated with acute myocardial infarction and angina pectoris, as well as ""visceral spasms"".","['Q07343', 'Q9Y233', 'Q01064', 'Q08499', 'Q13370', 'O76074']","Papaverine is a nonxanthine phosphodiesterase inhibitor for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. The main actions of Papaverine are exerted on cardiac and smooth muscle. Like qathidine, Papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by Papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one, and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the larger blood vessels, especially coronary, systemic peripheral, and pulmonary arteries.",COC1=C(OC)C=C(CC2=NC=CC3=CC(OC)=C(OC)C=C23)C=C1,"Perhaps by its direct vasodilating action on cerebral blood vessels, Papaverine increases cerebral blood flow and decreases cerebral vascular resistance in normal subjects; oxygen consumption is unaltered. These effects may explain the benefit reported from the drug in cerebral vascular encephalopathy.TargetActionsOrganismAcAMP-specific ','-cyclic phosphodiesterase BinhibitorHumansUcAMP and cAMP-inhibited cGMP ','-cyclic phosphodiesterase AinhibitorHumansUPhosphodiesterase enzymesinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Alkaloids', 'Benzylisoquinolines', 'Cardiovascular Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Drugs Used in Erectile Dysfunction', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Isoquinolines', 'Miscellaneous Vasodilatating Agents', 'Moderate Risk QTc-Prolonging Agents', 'Opiate Alkaloids', 'Papaverine and Derivatives', 'Phosphodiesterase Inhibitors', 'QTc Prolonging Agents', 'Urological Agents', 'Urologicals', 'Vasodilating Agents']" +DB00615,Rifabutin,Rifabutinis an antibiotic used to treat mycobacterium avium complex disease in patients with HIV.,"['P0A7Z4', 'P0A8V2', 'P0A8T7', 'P07900', 'P14625']","Rifabutin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (includingPseudomonas aeruginosa) and specificallyMycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifabutin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.",CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C2=C(C(O)=C3C)C(=O)C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)=C1NC3(CCN(CC3)CC(C)C)N=C21,"Rifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.TargetActionsOrganismADNA-directed RNA polymerase subunit alphainhibitorEscherichia coli (strain K)ADNA-directed RNA polymerase subunit betainhibitorEscherichia coli (strain K)ADNA-directed RNA polymerase subunit beta'inhibitorEscherichia coli (strain K)NHeat shock protein HSP -alphaother/unknownHumansNEndoplasminother/unknownHumans",[],"['Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics, Antitubercular', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (weak)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (moderate)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (weak)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs for Treatment of Tuberculosis', 'Heterocyclic Compounds, Fused-Ring', 'Lactams, Macrocyclic', 'P-glycoprotein inducers', 'Rifamycin Antimycobacterial', 'Rifamycins']" +DB00738,Pentamidine,Pentamidineis an antifungal agent used to treat Pneumocystis pneumonia in patients infected with HIV.,['O14717'],"Pentamidine is an antiprotozoal agent. It is an aromatic diamidine, and is known to have activity againstPneumocystis carinii. The exact nature of its antiprotozoal action is unknown.in vitrostudies with mammalian tissues and the protozoanCrithidia oncopeltiindicate that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids and proteins. Little is known about the drug's pharmacokinetics. The medication is also useful in Leishmaniasis and in prophylaxis against sleeping sickness caused byTrypanosoma brucei gambiense. Hydration before treatment lessens the incidence and severity of side effects, which include liver or kidney dysfunction, hypertension, hypotension, hypoglycemia, hypocalemia, leukopenia, thrombcytopenia, anemia, and allergic reaction. It is generally well-tolerated.",NC(=N)C1=CC=C(OCCCCCOC2=CC=C(C=C2)C(N)=N)C=C1,"The mode of action of pentamidine is not fully understood. It is thought that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids, and proteins.TargetActionsOrganismUtRNA (cytosine()-C())-methyltransferaseotherHumansUDNAintercalationHumans",[],"['Agents Against Leishmaniasis and Trypanosomiasis', 'Agents causing hyperkalemia', 'Amidines', 'Anti-Infective Agents', 'Antibiotics for Pneumocystis Pneumonia', 'Antifungal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Benzamidines', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Hyperglycemia-Associated Agents', 'Hypoglycemia-Associated Agents', 'Miscellaneous Antiprotozoals', 'Moderate Risk QTc-Prolonging Agents', 'Nephrotoxic agents', 'QTc Prolonging Agents', 'Trypanocidal Agents']" +DB00847,Cysteamine,Cysteamineis a cystine depleting agent used to treat the effects of cystinosis.,['P49146'],"Cystine accumulation is the cause of organ damage in cystinosis. Cysteamine prevents the accumulation of cystine crystals in the body and is specifically prescribed to prevent kidney and eye damage.4,9,12Cysteamine converts cystine into a form that may easily exit cells, preventing harmful accumulation.10",NCCS,"Individuals born without the ability to metabolize cystine suffer from cystinosis, a rare genetic disorder characterized by the widespread accumulation of cystine crystals throughout the body and eye tissues. The cystine crystals may cause considerable damage, particularly in the renal tissues and corneal tissues. In some cases, renal failure can occur during childhood if the condition is left untreated. Other organs that may be affected by cystinosis include the CNS, thyroid, pancreas, muscle tissues, and gonads.Cysteamine converts cystine to cysteine and cysteine-cysteamine mixed disulfides, reducing the buildup of corneal cystine crystals.This drug participates in a thiol-disulfide interchange reaction with lysosomes, leading to cysteine exit from the lysosome in patients diagnosed with cystinosis.TargetActionsOrganismUCystinecleavageHumansUNeuropeptide Y receptor type other/unknownHumans",[],"['Alimentary Tract and Metabolism', 'Amines', 'Amino Acids and Derivatives', 'Cystine Depleting Agents', 'Cystine Disulfide Reduction', 'EENT Drugs, Miscellaneous', 'Ethylamines', 'Mercaptoethylamines', 'Ophthalmics', 'Ophthalmologicals', 'Other Miscellaneous Therapeutic Agents', 'Sensory Organs', 'Sulfhydryl Compounds', 'Sulfur Compounds']" +DB11590,Thimerosal,"Thiomersal (INN), commonly known in the U.S. as thimerosal, is an organomercury compound. This compound is a well-established and widely used antiseptic and antifungal agent.","['Q99707', 'Q9UPY5', 'P54710']","Thimerosal is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties5. Thimerosal, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish21. Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury24.Prior to the recent initiative to reduce or eliminate thimerosal from childhood vaccines, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first 6 months of life was 187.5 micrograms. In the most recently formulated vaccines, the maximum cumulative exposure during the first 6 months of life should now be less than 3 micrograms of mercury. Currently, thimerosal may still be used in the early stages of manufacturing of certain childhood vaccines, however, only a trace remains after a chemical purification process. Note that the dose above is indicated for children 1-6 months of age is applicable only in the United States, and other countries may have varying indications20.",[Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O,"Although its mechanism of action is not fully understood, thimerosal inhibits sulfhydryl-containing active site of various enzymes and binds to sulfhydryl compounds, including glutathione, cysteine, and sulfhydryl groups of proteins. In addition, thimerosal activates the InsP calcium channel on the endoplasmic reticular membrane, thereby triggering the release of intracellular calcium resulting in a calcium-induced calcium-influx of extracellular calcium. Therefore, thimerosal may induce or inhibit various cellular functions that are dependent on the signaling of calcium.Ethylmercury is metabolized to inorganic mercury more rapidly than methylmercury. This difference in metabolism may account for kidney pathology that can result from toxic quantities. Also, whereas the increase in oxidative stress and induction of apoptosis observed in vitro with large doses ( μg/L to mg/L) of thimerosal may explain its damaging neurological effects. The effects of low-dose ethylmercury are not completely understood to date. It is known, however, that the shorter half-life of ethylmercury (the metabolite of thimerosal) allows for very limited opportunities of ethylmercury derived from thimerosal in vaccines.Ethylmercury is a lipophilic cation that is capable of crossing the blood-brain barrier. The octanol/water partition coefficients of methyl and ethylmercury are . to ., at intracellular pH and [Cl−], therefore, both organomercury compounds will primarily exist as intracellular lipophilic cations. It has been demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential. As the typical mitochondrial membrane potential of astrocytes and neurons is between – mV, one would expect the concentration of these organomercury compounds within mitochondria to be approximately times greater than the cytosolic concentration.TargetActionsOrganismUMethionine synthaseantagonistHumansUCystine/glutamate transporterantagonistHumansUSodium/potassium-transporting ATPase subunit gammaantagonistHumans",['Skin disinfection'],"['Alkylmercury Compounds', 'Antiseptics and Disinfectants', 'Cell-mediated Immunity', 'Compounds used in a research, industrial, or household setting', 'Dermatologicals', 'Ethylmercury Compounds', 'Increased Histamine Release', 'Mercurial Products', 'Organomercury Compounds', 'Organometallic Compounds', 'Pharmaceutic Aids', 'Pharmaceutical Preparations', 'Preservatives, Pharmaceutical', 'Standardized Chemical Allergen']" +DB06791,Lanreotide,"Lanreotideis a somatostatin analog used for the treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors and acromegaly.","['P30874', 'P35346']","Lanreotide exhibits antisecretory effects through cAMP suppression, and activation of ion currents such as K+ and Ca2+ which leads to hyperpolarization of the membrane and inhibition of Ca2+ mediated depolarization. Furthermore, through direct and indirect mechanisms, Lanreotide has potent antiproliferative effects.",[H]N([H])CCCCC1N([H])C(=O)C(CC2=CN([H])C3=CC=CC=C23)N([H])C(=O)C(CC2=CC=C(O)C=C2)N([H])C(=O)C(CSSCC(N([H])C(=O)C(N([H])C1=O)C(C)C)C(=O)N([H])C(C(C)O)C(=O)N([H])[H])N([H])C(=O)C(CC1=CC2=CC=CC=C2C=C1)N([H])[H],"Lanreotide is a somatostatin analogue (SSA) and has mainly inhibitory effects which are mediated via somatostatin receptors (SSTRs) and and include inhibition of growth hormone release in the brain. Tumor SSTR activation induces downstream cell cycle arrest and/or apoptosis, and also results in blunted production of substances that support tumor growth as well as tumor angiogenesis. This leads to the anti-proliferative effects of Lanreotide.TargetActionsOrganismUSomatostatin receptor type agonistHumansUSomatostatin receptor type agonistHumans",[],"['Acromegaly', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Hypoglycemia-Associated Agents', 'Hypothalamic Hormones', 'Nerve Tissue Proteins', 'Neuropeptides', 'Other Miscellaneous Therapeutic Agents', 'Pancreatic Hormones', 'Peptide Hormones', 'Peptides', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormone Release Inhibiting Hormones', 'Proteins', 'Somatostatin and Analogues', 'Somatostatin Receptor Agonists', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB00350,Minoxidil,Minoxidilis an antihypertensive vasodilating agent used for resistant hypertension that is symptomatic or has caused end organ damage.,"['P48048', 'P00797', 'P23219']","Minoxidil is an orally effective direct acting peripheral vasodilator that reduces elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance. Minoxidil is also used topically to treat androgenetic alopecia. Microcirculatory blood flow in animals is enhanced or maintained in all systemic vascular beds. In man, forearm and renal vascular resistance decline; forearm blood flow increases while renal blood flow and glomerular filtration rate are preserved. The predominant site of minoxidil action is arterial. Venodilation does not occur with minoxidil; thus, postural hypotension is unusual with its administration. The antihypertensive activity of minoxidil is due to its sulphate metabolite, minoxidil sulfate.",NC1=CC(=NC(N)=[N+]1[O-])N1CCCCC1,"Minoxidil is thought to promote the survival of human dermal papillary cells (DPCs) or hair cells by activating both extracellular signal-regulated kinase (ERK) and Akt and by preventing cell death by increasing the ratio of BCl-/Bax. Minoxidil may stimulate the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs. Minoxidil, when used as a vasodilator, acts by opening adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells. This vasodilation may also improve the viability of hair cells or hair follicles.TargetActionsOrganismAATP-sensitive inward rectifier potassium channel inducerHumansUReninNot AvailableHumansUProstaglandin G/H synthase inducerHumans",[],"['Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Arteriolar Smooth Muscle, Agents Acting On', 'Arteriolar Vasodilation', 'Arteriolar Vasodilator', 'Cardiovascular Agents', 'Dermatologicals', 'Direct Vasodilators', 'Hypotensive Agents', 'Misc. Skin and Mucous Membrane Agents', 'Piperidines', 'Potassium Channel Opener', 'Pyrimidine Derivatives', 'Pyrimidines', 'UGT1A1 Substrates', 'Vasodilating Agents']" +DB01065,Melatonin,Melatoninis an endogenous hormone produced by the pineal gland that regulates sleep-wake cycles and when provided exogenously has beneficial effects on sleep-onset latency; available as an over-the-counter supplement.,"['P48039', 'P49286', 'P03372', 'Q92753', 'P0DP23', 'P05164', 'P11678', 'P27797', 'P46597', 'P16083']","Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag. +MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions",COC1=CC2=C(NC=C2CCNC(C)=O)C=C1,"Melatonin is a derivative of tryptophan. It binds to melatonin receptor type A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors and , the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor (MT) and melatonin receptor (MT). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since . It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. +MT receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. +The binding of melatonin to melatonin receptors activates a few signaling pathways. MT receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell.TargetActionsOrganismAMelatonin receptor type AagonistHumansAMelatonin receptor type BagonistHumansUEstrogen receptor alphaantagonistHumansUNuclear receptor ROR-betaagonistHumansUCalmodulinNot AvailableHumansUMyeloperoxidaseinhibitorHumansUEosinophil peroxidaseinhibitorHumansUCalreticulinNot AvailableHumansUAcetylserotonin O-methyltransferaseNot AvailableHumansURibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHumans",[],"['Amines', 'Antioxidants', 'Biogenic Amines', 'Biogenic Monoamines', 'Biological Factors', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypnotics and Sedatives', 'Indoles', 'Melatonin Receptor Agonists', 'Melatonin, agonists', 'Nervous System', 'OAT3/SLC22A8 Inhibitors', 'Protective Agents', 'Psycholeptics', 'Tryptamines']" +DB01598,Imipenem,Imipenemis a carbapenem antibiotic normally administered with cilastatin to treat a variety of infections.,"['P0AD65', 'P02919', 'P02918', 'P42971', 'P72355', 'P52664']","Imipenem is a beta-lactam antibiotic belongings to the subgroup of carbapenems.12,13Imipenem is active against aerobic and anaerobic Gram positive as well as Gram negative bacteria includingPseudomonas aeruginosaand theEnterococcus. It exerts a bactericidal effects by disrupting cell wall synthesis.",[H][C@]12CC(SCC\N=C\N)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O,"Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria.,This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to penicillin-binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-, PBP-a, and PBP-b.This inhibition of PBPs prevents the bacterial cell from adding to the peptidoglycan polymer which forms the bacterial cell wall eventually leading to cell death.TargetActionsOrganismAPenicillin-binding protein inhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorEscherichia coli (strain K)UPenicillin-binding protein inhibitorBacillus subtilis (strain )UPenicillin-binding protein Not AvailableStaphylococcus aureusUBeta-lactamaseactivatorProteus vulgaris",[],"['Agents that reduce seizure threshold', 'Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Carbapenems', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Neurotoxic agents', 'Penem Antibacterial', 'Sulfur Compounds', 'Thienamycins']" +DB00734,Risperidone,"Risperidoneis a second-generation antipsychotic medication used to treat a number of mental health disorders including schizophrenia, bipolar mania, psychosis, or as an adjunct in severe depression.","['P28223', 'P14416', 'P35368', 'P18089', 'P35348', 'P18825', 'P35367', 'P28335', 'P28221', 'P08908', 'P34969', 'P21728']","The primary action of risperidone is to decrease dopaminergic and serotonergic pathway activity in the brain, therefore decreasing symptoms of schizophrenia and mood disorders.3,4Risperidone has a high binding affinity for serotonergic 5-HT2A receptors when compared to dopaminergic D2 receptors in the brain.2,3Risperidone binds to D2 receptors with a lower affinity than first-generation antipsychotic drugs, which bind with very high affinity. A reduction in extrapyramidal symptoms with risperidone, when compared to its predecessors, is likely a result of its moderate affinity for dopaminergic D2 receptors.7,5",CC1=C(CCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C(=O)N2CCCCC2=N1,"Though its precise mechanism of action is not fully understood, current focus is on the ability of risperidone to inhibit the D dopaminergic receptors and -HTA serotonergic receptors in the brain. Schizophrenia is thought to result from an excess of dopaminergic D and serotonergic -HTA activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively.,,D dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations.Risperidone binds transiently and with loose affinity to the dopaminergic D receptor, with an ideal receptor occupancy of -% for optimal effect.,Rapid dissociation of risperidone from the D receptors contributes to decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D dopaminergic receptors.,Low-affinity binding and rapid dissociation from the D receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D receptors is said to increase the risk of extrapyramidal symptoms and is therefore to be avoided.,,Increased serotonergic mesocortical activity in schizophrenia results in negative symptoms, such as depression and decreased motivation. The high-affinity binding of risperidone to -HTA receptors leads to a decrease in serotonergic activity. In addition, -HTA receptor blockade results in decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract. Dopamine level is therefore not completely inhibited.,Through the above mechanisms, both serotonergic and D blockade by risperidone are thought to synergistically work to decrease the risk of extrapyramidal symptoms.Risperidone has also been said to be an antagonist of alpha- (α), alpha- (α), and histamine (H) receptors.Blockade of these receptors is thought to improve symptoms of schizophrenia, however the exact mechanism of action on these receptors is not fully understood at this time.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUHistamine H receptorantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor DantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor antagonistHumansUD(L) dopamine receptorantagonistHumansUDopamine D receptorantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Pyrimidines', 'Pyrimidinones', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT1D Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB00948,Mezlocillin,"Semisynthetic ampicillin-derived acylureido penicillin. It has been proposed for infections with certain anaerobes and may be useful in inner ear, bile, and CNS infections.","['Q8XJ01', 'Q75Y35', 'P0AD65']","Mezlocillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name ""penicillin"" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Mezlocillin hasin vitroactivity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of mezlocillin results from the inhibition of cell wall synthesis and is mediated through mezlocillin binding to penicillin binding proteins (PBPs). Mezlocillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Mezlocillin can be used to treat susceptible strains ofH. influenzae,Klebsiellaspecies,Pseudomonasspecies,Proteus mirabilis,E. coli,Enterobacterspecies,Streptococcus faecelis,Peptococcusspecies,Peptostreptococcusspecies,Bacteriodesspecies (includingB. fragilis),Morganella morganii,Serratiaspecies,N. gonorrhoeae,P. vulgaris, andProvidencia rettgeri. This drug is discontinued in the U.S.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N1CCN(C1=O)S(C)(=O)=O)C1=CC=CC=C1)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, mezlocillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that mezlocillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)APenicillin-binding protein inhibitorStreptococcus pneumoniaeUPenicillin-binding protein inhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00399,Zoledronic acid,"Zoledronic acidis a bisphosphonate used to treat malignancy associated hypercalcemia, multiple myeloma, and bone metastasis from solid tumors.","['O95749', 'P14324']","Zoledronic acid is a third generation, nitrogen containing bisphosphonate that inhibits osteoclast function and prevents bone resorption.5The therapeutic window is wide as patients are unlikely to suffer severe effects from overdoses and the duration of action is long.14,15,16Patients should be counselled regarding the risk of electrolyte deficiencies, renal impairment, osteonecrosis of the jaw, atypical femoral fractures, bronchoconstriction, hepatic impairment, hypocalcemia, and embryo-fetal toxicity.14,15,16",OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O,"Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis.Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.Osteoclasts mediate resorption of bone.When osteoclasts bind to bone they form podosomes, ring structures of F-actin.Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes.,,Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.Nitrogen containing bisphosphonates such as zoledronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate.,These components are essential for post-translational prenylation of GTP-binding proteins like Rap.,The lack of prenylation of these proteins interferes with their function, and in the case of Rap, leads to apoptosis.,zoledronate also activated caspases which further contribute to apoptosis.,TargetActionsOrganismAGeranylgeranyl pyrophosphate synthaseinhibitorHumansAHydroxylapatiteantagonistbinderHumansAFarnesyl pyrophosphate synthaseinhibitorHumans",['Bone Mineral Density'],"['Bisphosphonates', 'Bone Density Conservation Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Imidazoles', 'Musculo-Skeletal System', 'Organophosphonates', 'Organophosphorus Compounds']" +DB00393,Nimodipine,Nimodipineis a calcium channel blocker used to improve neurological outcomes in patients with subarachnoid hemorrhage due to a ruptured intracranial aneurysm.,"['Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'P08235', 'P35869']","Nimodipine belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured congenital aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood brain barrier.",COCCOC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)C,"Although the precise mechanism of action is not known, nimodipine blocks intracellular influx of calcium through voltage-dependent and receptor-operated slow calcium channels across the membranes of myocardial, vascular smooth muscle, and neuronal cells. By specifically binding to L-type voltage-gated calcium channels, nimodipine inhibits the calcium ion transfer, resulting in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct effect involving the prevention of calcium overload in neurons may be responsible for nimodipine's clinical effect in patients with subarachnoid hemorrhage.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-FinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansUMineralocorticoid receptorantagonistHumansUAryl hydrocarbon receptoragonistHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Nicotinic Acids', 'P-glycoprotein inhibitors', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00816,Orciprenaline,"Orciprenalineis a beta-2 adrenergic agonist used to treat bronchospasm, asthma, and COPD.",['P07550'],"Orciprenaline (also known as metaproterenol), a synthetic amine, is structurally and pharmacologically similar to isoproterenol. Orciprenaline is used exclusively as a bronchodilator. The pharmacological effects of beta adrenergic agonist drugs, such as orciprenaline, are at least in part attributable to stimulation through beta adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3',5'- adenosine monophosphate (c-AMP). Increased cAMP levels lead to relaxation of bronchial smooth muscles and inhibition of the release of inalammatory mediators from mast cells that are involved in promoting immediate hypersensitivity .",CC(C)NCC(O)C1=CC(O)=CC(O)=C1,"Orciprenaline stimulates the β-adrenergic receptor expressed in the lungs, uterus, and vasculature supplying skeletal muscles by acting as a moderately selective agonist. It exerts minimal or no effect on alpha-adrenergic receptors. Intracellularly, the actions of orciprenaline are mediated by cAMP, the production of which is augmented by beta stimulation. The drug is believed to work by activating adenylate cyclase, the enzyme responsible for producing the cellular mediator cAMP.TargetActionsOrganismABeta- adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Benzene Derivatives', 'Bronchodilator Agents', 'Catecholamines', 'Catechols', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Neurotransmitter Agents', 'Non-selective Beta-adrenergic Agonists', 'Peripheral Nervous System Agents', 'Phenols', 'Reproductive Control Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetics', 'Tocolytic Agents']" +DB00831,Trifluoperazine,"Trifluoperazineis a phenothiazine used to treat depression, anxiety, and agitation.","['P14416', 'Q9NYX4', 'P35348', 'P0DP23', 'P63316', 'P26447']",Trifluoperazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Trifluoperazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.,CN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(C=C3)C(F)(F)F)CC1,"Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D and D receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.TargetActionsOrganismADopamine D receptorantagonistHumansANeuron-specific vesicular protein calcyonantagonistHumansAAlpha-A adrenergic receptorantagonistHumansUCalmodulininhibitorHumansUTroponin C, slow skeletal and cardiac musclesNot AvailableHumansUProtein S-AinhibitorHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenothiazines', 'Phenothiazines With Piperazine Structure', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Sulfur Compounds', 'Tranquilizing Agents', 'UGT1A4 substrates']" +DB00687,Fludrocortisone,Fludrocortisoneis a mineralocorticoid used to treat adrenocortical insufficiency and salt-losing adrenogenital syndrome.,"['P08235', 'P04150']","Fludrocortisone is a synthetic mineralocorticoid used to replace endogenousaldosteronein conditions resulting in missing or inadequate endogenous synthesis.14,15It acts on the kidneys to increase both sodium reabsorption and potassium excretion.13,11As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days15despite a relatively short plasma half-life.6,9,10Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.14",[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure.In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone.Fludrocortisone binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na+-K+-ATPase on the basolateral side.These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. Fludrocortisone may also exert a direct effect on plasma sodium levels via action at the Na+-H+exchanger found in the apical membrane of renal tubule cells.Fludrocortisone also acts on glucocorticoid receptors, albeit with a much lower affinity - the glucocorticoid potency of fludrocortisone is approximately - times that of endogenous cortisol, whereas its mineralocorticoid potency is - times greater.TargetActionsOrganismAMineralocorticoid receptoragonistHumansUGlucocorticoid receptoragonistHumans",[],"['11-Hydroxycorticosteroids', '17-Hydroxycorticosteroids', 'Adrenal Cortex Hormones', 'Adrenals', 'Anti-Inflammatory Agents', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydroxycorticosteroids', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Mineralocorticoids', 'Pregnenes', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB00655,Estrone,Estroneis an estrogen used to treat perimenopausal and postmenopausal symptoms.,"['P03372', 'Q92731', 'P10275', 'P11511', 'P04278']","Estrone, a synthetically prepared or naturally occurring steroidal estrogen obtained from pregnant equine urine, is the primary circulating estrogen after menopause. Estrone is naturally derived from the peripheral conversion of androstenedione by an aromatase enzyme found in adipose tissues and is converted to estradiol in peripheral tissues. The estrogenic potency of estrone is one third that of estradiol. Estropipate is piperazine-stabilized estrone sulfate. Estrone, and estropipate are used to treat abnormalities related to gonadotropin hormone dysfunction, vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated with menopause, and for the prevention of osteoporosis due to estrogen deficiency.",[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3,"Estrogens enter the cells of responsive tissues (e.g. female organs, breasts, hypothalamus, pituitary) where they interact with estrogen receptors. Hormone-bound estrogen receptors dimerize, translocate to the nucleus of cells and bind to estrogen response elements (ERE) of genes. Binding to ERE alters the transcription rate of affected genes. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) release from the anterior pituitary.TargetActionsOrganismAEstrogen receptor alphaagonistHumansUEstrogen receptor betaNot AvailableHumansUAndrogen receptorNot AvailableHumansUCytochrome P ANot AvailableHumansUSex hormone-binding globulinNot AvailableHumans",[],"['17-Ketosteroids', 'Adrenal Cortex Hormones', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Estrogens', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Ketosteroids', 'Natural and Semisynthetic Estrogens, Plain', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Thyroxine-binding globulin inducers']" +DB00603,Medroxyprogesterone acetate,"Medroxyprogesterone acetateis a progestin used as a contraceptive and in the treatment of secondary amenorrhea, abnormal uterine bleeding, pain from endometriosis, endometrial and renal carcinomas, paraphilia in males, and GnRH-dependent precocious puberty.","['P06401', 'P03372', 'P08183', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines.11,6MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long.2,3The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly.10,11,12,13,14Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future.10,11,12,13,14",[H][C@@]12CC[C@](OC(C)=O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)CC[C@]12C,"Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy.This action also thins the endometrium.MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium.MPA can also induce p dependant apoptosis in certain cancer cell lines,and inhibit GABA-A receptors.TargetActionsOrganismAProgesterone receptoragonistHumansAEstrogen receptor alphaagonistHumansUP-glycoprotein inhibitorHumansUGABA(A) ReceptorinhibitorHumans","['Contraception', 'Estrogen Replacement Therapy', 'Hormonal Contraception therapy']","['Adrenal Cortex Hormones', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptive Agents, Male', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Contraceptives, Oral, Synthetic', 'Corpus Luteum Hormones', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydroxyprogesterones', 'Hyperglycemia-Associated Agents', 'P-glycoprotein inhibitors', 'Pregnanes', 'Pregnen (4) Derivatives', 'Pregnenediones', 'Pregnenes', 'Progesterone and Derivatives', 'Progesterone Congeners', 'Progestin Contraceptives', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00882,Clomifene,Clomifeneis a medication used to induce ovulation.,"['P03372', 'P04278']","Clomifene (previously clomiphene) is an orally administered, non steroidal, ovulatory stimulant that acts as a selective estrogen receptor modulator (SERM). Clomifene can lead to multiple ovulation, and hence increase the risk of conceiving twins. In comparison to purified FSH, the rate of ovarian hyperstimulation syndrome is low. There may be an increased risk of ovarian cancer and weight gain. Clomifene is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular estrogen receptors. Clomifene initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event, in response to a course of clomifene therapy, is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.",CCN(CC)CCOC1=CC=C(C=C1)C(=C(Cl)C1=CC=CC=C1)C1=CC=CC=C1,"Clomifene has both estrogenic and anti-estrogenic properties, but its precise mechanism of action has not been determined. Clomifene appears to stumulate the release of gonadotropins, follicle-stimulating hormone (FSH), and leuteinizing hormone (LH), which leads to the development and maturation of ovarian follicle, ovulation, and subsequent development and function of the coprus luteum, thus resulting in pregnancy. Gonadotropin release may result from direct stimulation of the hypothalamic-pituitary axis or from a decreased inhibitory influence of estrogens on the hypothalamic-pituitary axis by competing with the endogenous estrogens of the uterus, pituitary, or hypothalamus. Clomifene has no apparent progestational, androgenic, or antrandrogenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.TargetActionsOrganismAEstrogen receptor alphaantagonistagonistHumansUSex hormone-binding globulinNot AvailableHumans",[],"['Benzene Derivatives', 'Benzylidene Compounds', 'Clomiphene', 'Estrogen Agonist-antagonists', 'Estrogen Agonist/Antagonist', 'Estrogen Antagonists', 'Estrogen Receptor Modulators', 'Fertility Agents', 'Fertility Agents, Female', 'Genito Urinary System and Sex Hormones', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Ovulation Stimulants, Synthetic', 'P-glycoprotein substrates', 'Reproductive Control Agents', 'Selective Estrogen Receptor Modulators', 'Sex Hormones and Modulators of the Genital System', 'Stilbenes']" +DB01094,Hesperetin,"Hesperetin belongs to the flavanone class of flavonoids. Hesperetin, in the form of its glycosidehesperidin, is the predominant flavonoid in lemons and oranges.","['P55157', 'P35610', 'P04278', 'O75908']","Hesperetin is a cholesterol lowering flavanoid found in a number of citrus juices. It appears to reduce cholesteryl ester mass and inhibit apoB secretion by up to 80%. Hesperetin may have antioxidant, anti-inflammatory, anti-allergic, hypolipidemic, vasoprotective and anticarcinogenic actions.",COC1=C(O)C=C(C=C1)[C@@H]1CC(=O)C2=C(O)C=C(O)C=C2O1,"Hesperetin reduces or inhibits the activity of acyl-coenzyme A:cholesterol acyltransferase genes (ACATand ACAT) and it reduces microsomal triglyceride transfer protein (MTP) activity. Hesperetin also seems to upregulate the LDL receptor. This leads to the reduced assembly and secretion of apoB-containing lipoproteins and enhanced reuptake of those lipoproteins, thereby lowering cholesterol levels.TargetActionsOrganismAMicrosomal triglyceride transfer protein large subunitantagonistHumansASterol O-acyltransferase inhibitorHumansUSex hormone-binding globulinNot AvailableHumansUSterol O-acyltransferase inhibitorHumans",[],"['BCRP/ABCG2 Inhibitors', 'Benzopyrans', 'Carbohydrates', 'Chromones', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Flavanones', 'Flavonoids', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring', 'Pyrans']" +DB00482,Celecoxib,"Celecoxibis an NSAID used to treat osteoarthritis, rheumatoid arthritis, acute pain, menstrual symptoms, and to reduce polyps is familial adenomatous polyposis.","['P35354', 'P00918', 'P07451', 'H3BUU9', 'O15530', 'Q99519']","Celecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding.28A note on the risk of cardiovascular eventsSignificant concerns regarding the safety of COX-2 selective NSAIDs emerged in the early 2000s.Rofecoxib, another member of the COX-2 inhibitor drug class, also known as Vioxx, was withdrawn from the market due to prothrombotic cardiovascular risks.30Following an FDA Advisory Committee meeting in 2005, in which data from large clinical outcome trials were evaluated, the FDA concluded that the risk for cardiovascular thrombotic events for both COX-2 selective NSAIDs and nonselective NSAIDs was evident.23It was determined that the benefits of celecoxib treatment, however, outweighed the risks.30Postmarketing cardiovascular outcomes trial (PRECISION) revealed that the lowest possible dose of celecoxib was similar in cardiovascular safety to moderate strength doses of both naproxen and ibuprofen. Patients who had previous cardiovascular events including acute MI, coronary revascularization, or coronary stent insertion were not evaluated in the trial. It is not advisable to administer NSAIDS to these groups of patients.23",CC1=CC=C(C=C1)C1=CC(=NN1C1=CC=C(C=C1)S(N)(=O)=O)C(F)(F)F,"Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX- and COX-), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase- (COX-) enzyme. COX- is expressed heavily in inflamed tissues where it is induced by inflammatory mediators.The inhibition of this enzyme reduces the synthesis of metabolites that include prostaglandin E (PGE), prostacyclin (PGI), thromboxane (TXA), prostaglandin D (PGD), and prostaglandin F (PGF). Resultant inhibition of these mediators leads to the alleviation of pain and inflammation.,By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract.Celecoxib poses less of an ulceration risk than other NSAIDS, owing to its decreased effect on gastric mucosal prostaglandin synthesis when compared to placebo.Celecoxib exerts anticancer effects by binding to the cadherin- (CDH)protein, which is thought to be involved in the progression of tumors, and inhibiting the -phosphoinositide-dependent kinase- (PDK-) signaling mechanism.,In addition, celecoxib has been found to inhibit carbonic anhydrase enzymes and , further enhancing its anticancer effects.,As mentioned in the pharmacodynamics section of this drug entry, celecoxib may cause an increased risk of thrombotic events. The risk of thrombosis resulting from COX- inhibition is caused by the vasoconstricting actions of thromboxane A, leading to enhanced platelet aggregation, which is uncontrolled when the actions of prostacyclin, a platelet aggregation inhibitor, are suppressed through the inhibition of COX-.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCadherin-inhibitorHumansU-phosphoinositide-dependent protein kinase inhibitorHumansASialidase-inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amides', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'Benzenesulfonamides', 'BSEP/ABCB11 Inhibitors', 'Central Nervous System Agents', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cyclooxygenase-2 (COX-2) Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Methemoglobinemia Associated Agents', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Pyrazoles', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB01188,Ciclopirox,Ciclopiroxis a broad-spectrum topical antifungal agent used to treat mild to moderate onychomycosis of fingernails and toenails in immunocompetent patients.,['P05023'],"Ciclopirox is a broad-spectrum antifungal medication that also has antibacterial and anti-inflammatory properties. Its main mode of action is thought to be its high affinity for trivalent cations, which inhibit essential co-factors in enzymes. Ciclopirox exhibits either fungistatic or fungicidal activity in vitro against a broad spectrum of fungal organisms, such as dermatophytes, yeasts, dimorphic fungi, eumycetes, and actinomycetes. In addition to its broad spectrum of action, ciclopirox also exerts antibacterial activity against many Gram-positive and Gram-negative bacteria. Furthermore, the anti-inflammatory effects of ciclopirox have been demonstrated in human polymorphonuclear cells, where ciclopirox has inhibited the synthesis of prostaglandin and leukotriene. Ciclopirox can also exhibit its anti-inflammatory effects by inhibiting the formation of 5-lipoxygenase and cyclooxygenase.",CC1=CC(=O)N(O)C(=C1)C1CCCCC1,"Unlike antifungals such as itraconazole and terbinafine, which affect sterol synthesis, ciclopirox is thought to act through the chelation of polyvalent metal cations, such as Fe+and Al+. These cations inhibit many enzymes, including cytochromes, thus disrupting cellular activities such as mitochondrial electron transport processes and energy production. Ciclopirox also appears to modify the plasma membrane of fungi, resulting in the disorganization of internal structures. The anti-inflammatory action of ciclopirox is most likely due to inhibition of -lipoxygenase and cyclooxygenase. +ciclopirox may exert its effect by disrupting DNA repair, cell division signals and structures (mitotic spindles) as well as some elements of intracellular transport.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-binderHumans",[],"['Anti-Infective Agents', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Cyclohexanes', 'Cycloparaffins', 'Decreased DNA Replication', 'Decreased Protein Synthesis', 'Decreased RNA Replication', 'Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hydroxypyridones', 'Protein Synthesis Inhibitors', 'Pyridines', 'Pyridones', 'Vaginal Creams, Foams, and Jellies']" +DB01380,Cortisone acetate,Cortisone acetateis a steroid hormone used for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and endocrine disorders associated with inadequate production of steroid hormones.,"['P04150', 'P04083']","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.3The duration of action is moderate as it is generally given once daily.8Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.3Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.3",[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUAnnexin AinducerHumans",[],"['17-Hydroxycorticosteroids', 'Adrenal Cortex Hormones', 'Adrenals', 'Anti-Inflammatory Agents', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydroxycorticosteroids', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'OAT3/SLC22A8 Substrates', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Pregnanes', 'Pregnenes', 'Steroids']" +DB01420,Testosterone propionate,Testosterone propionateis a slow-release anabolic steroid no longer used commonly for the treatment of androgen deficiency or promotion of anabolic effects on muscles.,['P10275'],The administration of testosterone propionate can induce production of proteins related to male sexual development.5Clinical trials have shown a decrease in plasma LH after the administration of testosterone propionate.1,[H][C@@]12CC[C@H](OC(=O)CC)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to alpha-dihydrotestosterone (DHT) by the cytoplasmic enzyme alpha-reductase. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.TargetActionsOrganismAAndrogen receptoragonistHumans",[],"['Androgens', 'Androstanes', 'Androstenes', 'Androstenols', 'COMT Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'P-glycoprotein substrates', 'Steroids', 'Testosterone and derivatives', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors', 'UGT1A1 Inducers']" +DB00328,Indomethacin,Indomethacinis a nonsteroidal anti-inflammatory (NSAID) used for symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants.,"['P35354', 'P14555', 'P23219', 'Q8N8N7', 'P37231', 'Q04760', 'Q9Y5Y4', 'Q07869', 'P42330', 'P19525', 'P23219', 'P35354']","Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation.13Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength.13In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.13In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment.13The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity.1There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.1",COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(O)=O,"Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX- is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A, while COX- is expressed in response to injury or inflammation.Constitutively expressed, the COX- enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G and PGG to PGH.COX- is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX- also catalyzes the conversion of arachidonic acid to PGG and PGG to PGH. In the COX--mediated pathway, PGH is further converted to PGE and PGI (also known as prostacyclin). PGE is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation.The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis.At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth.Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE mediates an opposite effect to that of oxygen. PGE dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus.By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIFα, inhibiting protein synthesis.,TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAPhospholipase A, membrane associatedinhibitorHumansUProstaglandin G/H synthase inhibitorHumansUProstaglandin reductase inhibitorHumansUPeroxisome proliferator-activated receptor gammaactivatorHumansULactoylglutathione lyaseinhibitorHumansUProstaglandin D receptor other/unknownHumansUPeroxisome proliferator-activated receptor alphaagonistHumansUAldo-keto reductase family member CinhibitorHumansUInterferon-induced, double-stranded RNA-activated protein kinaseinducerHumansAHuman CyclooxygenasesinhibitorHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antigout Preparations', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'BSEP/ABCB11 Substrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypoglycemia-Associated Agents', 'Immunosuppressive Agents', 'Indoles', 'Musculo-Skeletal System', 'Myelosuppressive Agents', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Inhibitors', 'Ophthalmologicals', 'Other Nonsteroidal Anti-inflammatory Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Sensory Organs', 'Sensory System Agents', 'Tocolytic Agents', 'Topical Products for Joint and Muscular Pain', 'UGT1A1 Inhibitors', 'UGT1A1 Substrates', 'UGT1A9 Substrates', 'UGT2B7 Inhibitors', 'UGT2B7 substrates']" +DB01100,Pimozide,Pimozideis an antipsychotic used to manage debilitating motor and phonic tics in patients with Tourette's Disorder.,"['P14416', 'P35462', 'Q12809', 'P0DP23']","Pimozide is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both pimozide's therapeutic and untoward effects. In addition, pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized. Pimozide also has less potential for inducing sedation and hypotension as it has more specific dopamine receptor blocking activity than other neuroleptic agents (and is therefore a suitable alternative to haloperidol).",FC1=CC=C(C=C1)C(CCCN1CCC(CC1)N1C(=O)NC2=CC=CC=C12)C1=CC=C(F)C=C1,The ability of pimozide to suppress motor and phonic tics in Tourette's Disorder is thought to be primarily a function of its dopaminergic blocking activity. Pimozide binds and inhibits the dopamine D receptor in the CNS.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansAPotassium voltage-gated channel subfamily H member inhibitorHumansUCalmodulininhibitorHumans,[],"['Agents that reduce seizure threshold', 'Anti-Dyskinesia Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Benzimidazoles', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diphenylbutylpiperidine Derivatives', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Miscellaneous Antipsychotics', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Tranquilizing Agents']" +DB01151,Desipramine,Desipramineis a tricyclic antidepressant used in the treatment of depression.,"['P23975', 'P31645', 'P28223', 'P07550', 'P08588', 'P17405', 'P35367', 'P35348', 'P35368', 'P25100', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P08908', 'P28335', 'P14416', 'P08913', 'P18089', 'P18825']","Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms.",CNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12,"Desipramine is a tricyclic antidepressant (TCA) that selectively blocks reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases stimulation of the post-synaptic neuron. Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor AantagonistHumansUBeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorotherHumansUSphingomyelin phosphodiesteraseinhibitorHumansNHistamine H receptorantagonistHumansNAlpha- adrenergic receptorsantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor CbinderHumansUDopamine D receptorbinderHumansUAlpha- adrenergic receptorsbinderHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dibenzazepines', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB00499,Flutamide,Flutamideis an antiandrogen used for locally confined stage B2-C and D-2 metastatic prostate carcinoma.,"['P10275', 'P35869', 'O75469']","Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g. castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration.",CC(C)C(=O)NC1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F,"Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.TargetActionsOrganismAAndrogen receptorantagonistHumansUAryl hydrocarbon receptoragonistHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['Amides', 'Amines', 'Androgen Receptor Antagonists', 'Androgen Receptor Inhibitors', 'Anilides', 'Aniline Compounds', 'Antiandrogens', 'Antiandrogens, non-steroidal', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Methemoglobinemia Associated Agents']" +DB00890,Dienestrol,Dienestrolis a non steroidal estrogen used to treat atrophic vaginitis and kraurosis vulvae.,"['P03372', 'P04278']","Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).",[H]\C(C)=C(/C(=C(\[H])C)/C1=CC=C(O)C=C1)\C1=CC=C(O)C=C1,"Dienestrol is a synthetic, non-steroidal estrogen. Estrogens passively diffuse into target cells of responsive tissues, complex with the estrogen receptors, and enter the cell's nucleus to initiate or enhance gene transcription of protein synthesis after binding to DNA.TargetActionsOrganismAEstrogen receptor alphaagonistHumansUSex hormone-binding globulinNot AvailableHumans",[],"['Benzene Derivatives', 'Benzyl Compounds', 'Benzylidene Compounds', 'Bibenzyls', 'Dihydrostilbenoids', 'Estrogens', 'Estrogens, Non-Steroidal', 'Genito Urinary System and Sex Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Phenols', 'Sex Hormones and Modulators of the Genital System', 'Stilbenes', 'Stilbestrols', 'Synthetic Estrogens, Plain']" +DB01101,Capecitabine,"Capecitabineis a nucleoside metabolic inhibitor indicated to treat different gastrointestinal, including pancreatic cancer, and breast cancer.",['P04818'],"Capecitabine is a fluoropyrimidine carbamate belonging to a group of antineoplastic agents called antimetabolites, which kill cancerous cells by interfering with DNA synthesis.39,26It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to 5-fluorouracil (5-FU) by enzymes that are expressed in higher concentrations in many tumors.40Capecitabine was designed specifically to overcome the disadvantages of 5-FU and to mimic the infusional pharmacokinetics of 5-FU without the associated complexity and complications of central venous access and infusion pumps.39Particularly, since the enzymes converting 5-FU into active metabolites exist in the gastrointestinal tract, infusion of 5-FU can have gastrointestinal toxicity while also losing efficacy.41Since capecitabine can be transported intact across the intestinal mucosa, it can be selectively delivered 5-FU to tumor tissues through enzymatic conversion preferentially inside tumor cells.415-FU exerts its pharmacological action through the inhibition and interference of 3 main targets: thymidylate synthase, DNA, and RNA, leading through protein synthesis disruption and apoptosis.26,20Population-based exposure-effect analyses demonstrated a positive association between AUC of 5-FU and grade 3-4 hyperbilirubinemia.42",CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O,"Capecitabine is metabolized to -fluorouracil in vivo by carboxylesterases, cytidine deaminase, and thymidine phosphorylase/uridine phosphorylase sequentially.,,,,-fluorouracil is further metabolized through a series of enzymatic reactions into main active metabolites: -fluorouridine triphosphate (-FUTP), -fluoro-’-deoxyuridine monophosphate (-FdUMP), and -fluorodeoxyuridine triphosphate (-FdUTP).,,. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N--methylenetetrahydrofolate (CHTHF), bind to thymidylate synthase (TS) to form a covalently bound ternary complex.TS is an enzyme that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).,Under normal physiological conditions, dUMP binds to TS first before CHTHF, followed by a , or Michael addition from the pyrimidine C ()atom to the Cys nucleophile.,If correctly positioned, dUMP, CHTHF, and TS would form a ternary complex to facilitate the donation of the methyl group from CHTHF to dUMP.However, the substitution of dUMP with FdUMP results in a new time-dependent TS–FdUMP–CHTHF complex. Since the fluorine group prevents dissociation of FdUMP from the pyrimidine ring, the whole complex is rendered irreversibly deactivated, terming this reaction ""suicide inhibition"".,TS inhibition prevents the conversion of dUMP to dTMP, depleting the pool of dTMP that could be phosphorylated into dTTP to be incorporated as DNA nucleotides. This disrupts the nucleotides balance, particularly the the ATP/dTTP ratio, thus impairing DNA synthesis and repair and causing apoptosis.,-FdUMP can also be phosphorylated into -FdUTP, further increasing the pool of dUTP base to potentially overwhelm the activity of dUTPase.Coupled with the decrease in dTTP, -FdUMP, and -FdUTP increase the probability of mistakenly incorporating a uracil base into DNA strands in place of thymine. Although this mistake can often be resolved by the nucleotide excision repair enzyme uracil-DNA-glycosylase (UDG), the high (F)dUTP/dTTP ratio would result in re-incorporation of uracil into DNA, leading to a futile cycle of misincorporation, excision, and repair.,Repeated base excision repair can result in abasic sites, which can lead to DNA mutagenesis and thus protein miscoding, replication forks collapse, and DNA fragmentation through single or double strand breaks,,,However, several reports have found that the incorporation of uracil in genomic DNA does not significantly affect the cytotoxicity of -FU, suggesting that the cytotoxic effect of -FU is dominated by the perturbation of RNA through -FUTP.,Similar to -dFUTP, -FUTP can be mistakenly incorporated into RNA in place of regular UTP and disrupt regular RNA biology through various mechanisms. -FUTP can be incorporated into the spliceosomal U snRNA at pseudouridylated sites to prevent further pseudouridylation and thus pre-mrNA splicing. -FUTP can also change the structure of U and U snRNA and reduce the turnover rate of U snrNA once incorporated.For tRNA, -FUTP can affect tRNA's post-transcriptional RNA modifications activity, particularly by inhbiting pseudouridine synthase through formation of covalent complex.,Recently, the effect of -FUTP on miRNAs and lncRNA was also observed through profound changes in expression, although the precise mechanism is still unknown.,,Although the main mechanism of -FU cytotoxicity was thought to be attributed to DNA damages, recent reports have shown that the majority of -FU pharmacological action is mediated through RNA, since -FU is accumulated ~- to  -fold more in RNA compared to that of DNA.TargetActionsOrganismADNAincorporation into and destabilizationinhibition of synthesisHumansARNAincorporation into and destabilizationHumansAThymidylate synthaseinhibitorHumans",['Chemotherapy'],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Cytidine Deaminase Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fluoropyrimidines', 'Fluorouracil and prodrugs', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Pyrimidine Analogues', 'Toxic Actions']" +DB00007,Leuprolide,"Leuprolideis a peptide-based GnRH receptor superagonist used for the palliative treatment of prostate cancer, uterine leiomyomata, endometriosis, and central precocious puberty.",['P30968'],"Leuprolide is a gonadotropin-releasing hormone (GnRH) analogue that functions as a GnRH receptor superagonist.3,4After an initial spike in GnRH-mediated steroidal production, including testosterone and estradiol, prolonged use results in a significant drop in circulating steroid levels, in line with those produced through other forms of androgen-deprivation therapy (ADT).1,2,3The corresponding hormonal/steroidal changes produce specific adverse effects in different patient populations.In women undergoing treatment for endometriosis or uterine leiomyomata, careful consideration regarding pregnancy status is advised. The initial increase in estradiol levels may worsen symptoms such as pain and bleeding. Long-term use of leuprolide is associated with loss of bone mineral density. Patients co-administered withnorethisteronemay experience sudden vision loss, proptosis, diplopia, migraine, thrombophlebitis, and pulmonary embolism and may also be at higher risk of cardiovascular disease. Patients with a history of depression may experience severe recurrence of depressive symptoms.5,10In men undergoing palliative treatment for advanced/metastatic prostate cancer, short-term spikes in testosterone levels may cause tumour flare and associated symptoms such as bone pain, hematuria, neuropathy, bladder and/or ureteral obstruction, and spinal cord compression. In addition, patients are at increased risk of developing hyperglycemia, diabetes, and cardiovascular disease, which may manifest through myocardial infarction, stroke, cardiac death, or prolonged QT/QTc interval. In addition, Leuprolide may cause convulsions and embryo-fetal toxicity.6,9In pediatric patients undergoing treatment for central precocious puberty (CPP), the initial steroidal spike may be associated with increased clinical signs of puberty within 2-4 weeks of treatment initiation. In addition, leuprolide may cause convulsions and psychiatric symptoms, including irritability, impatience, aggression, anger, and crying.7,8",CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H]1CCC(=O)N1,"Gonadotropin-releasing hormone (GnRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal (HPG) axis. GnRH binds to corresponding receptors (GnRHRs) on the anterior pituitary gonadotropes, which in turn release luteinizing hormone (LH) and follicle-stimulating hormone (FSH); these, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol.,Despite the variety of conditions indicated for treatment with leuprolide, the mechanism of action underlying efficacy is the same in all cases. As a GnRHR agonist, leuprolide binds to and initially activates downstream LH and FSH release; this initial spike in gonadotropin levels is responsible for some of the adverse effects associated with treatment. After - weeks of treatment, continuous stimulation of GnRHR results in feedback inhibition and significant downregulation of LH, FSH, and their corresponding downstream effects, producing a therapeutic benefit. These effects are reversible upon treatment discontinuation.,,,,,,,,,TargetActionsOrganismAGonadotropin-releasing hormone receptoragonistHumans",['Palliative Treatment'],"['Adrenal Cortex Hormones', 'Agents Causing Muscle Toxicity', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Fertility Agents', 'Fertility Agents, Female', 'Gonadotropin Releasing Hormone Receptor Agonist', 'Gonadotropin Releasing Hormone Receptor Agonists', 'Gonadotropin-releasing hormone agonist', 'Gonadotropins', 'Hormones and Related Agents', 'Hyperglycemia-Associated Agents', 'Hypothalamic Hormones', 'Moderate Risk QTc-Prolonging Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptides', 'Photosensitizing Agents', 'Pituitary Hormone-Releasing Hormones', 'Proteins', 'QTc Prolonging Agents', 'Reproductive Control Agents']" +DB00262,Carmustine,"Carmustineis an alkylating agent used in the treatment of various malignancies, including brain tumours and multiple myeloma, among others.",['P00390'],"Carmustine is one of the nitrosoureas indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.",ClCCNC(=O)N(CCCl)N=O,"Carmustine causes cross-links in DNA and RNA, leading to the inhibition of DNA synthesis, RNA production and RNA translation (protein synthesis). Carmustine also binds to and modifies (carbamoylates) glutathione reductase. This leads to cell death.TargetActionsOrganismARNAother/unknownHumansAGlutathione reductase, mitochondrialinhibitorHumansADNAother/unknownHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Amides', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nitroso Compounds', 'Nitrosourea Compounds', 'Nitrosoureas', 'Noxae', 'Toxic Actions']" +DB00293,Raltitrexed,Raltitrexedis a folate analog thymidylate synthase inhibitor used in the treatment of advanced colorectal cancer.,"['P04818', 'Q05932']","Raltitrexed belongs to a group of medicines known as antimetabolites. It is used to treat cancer of the colon and rectum. It may also be used to treat other kinds of cancer, as determined by your doctor. Raltitrexed blocks an enzyme needed by the cell to live. This interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by raltitrexed, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern.",CN(CC1=CC2=C(NC(C)=NC2=O)C=C1)C1=CC=C(S1)C(=O)N[C@@H](CCC(O)=O)C(O)=O,"Raltitrexed is an antineoplastic Agents and folic acid antagonists. Raltitrexed inhibits thymidylate synthase (TS) leading to DNA fragmentation and cell death. It is transported into cells via a reduced folate carrier. Inside the cell Raltitrexed is extensively polyglutamated, which enhances thymidylate synthase inhibitory power and duration. Inhibition of this enzyme results in decreased synthesis of thymidine triphosphate which is required for DNA synthesis.TargetActionsOrganismAThymidylate synthaseinhibitorHumansUFolylpolyglutamate synthase, mitochondrialantagonistHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Enzyme Inhibitors', 'Folic Acid Analogues', 'Folic Acid Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Sulfur Compounds', 'Thymidylate Synthase, antagonists & inhibitors', 'Toxic Actions']" +DB00441,Gemcitabine,"Gemcitabineis a nucleoside metabolic inhibitor used as adjunct therapy in the treatment of certain types of ovarian cancer, non-small cell lung carcinoma, metastatic breast cancer, and as a single agent for pancreatic cancer.","['P23921', 'P04818', 'P30085']","Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary.4Gemcitabine demonstrated cytotoxic effects against a broad range of cancer cell linesin vitro. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer.2Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage.2Gemcitabine inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months.3In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months.2Gemcitabine causes dose-limiting myelosuppression, such as anemia, leukopenia, neutropenia, and thrombocytopenia; however, events leading to discontinuation tend to occur less than 1% of the patients. Gemcitabine can elevate ALT, AST and alkaline phosphatase levels.3",NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F,"Gemcitabine is a potent and specific deoxycytidine analog. After uptake into malignant cells, gemcitabine is phosphorylated by deoxycytidine kinase to form gemcitabine monophosphate, which is then converted to the active compounds, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These active metabolites are nucleosides that mediate antitumour effects. dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, thereby competitively inhibiting DNA chain elongation. The non-terminal position of dFdCTP in the DNA chain prevents detection of dFdCTP in the chain and repair by proof-reading ′′-exonuclease: this process is referred to as ""masked DNA chain termination."" Incorporation of dFdCTP into the DNA chain ultimately leads to chain termination, DNA fragmentation, and apoptotic cell death of malignant cells.,,Gemcitabine has self-potentiating pharmacological actions that can increase the probability of successful incorporation of gemcitabine triphosphate into the DNA chain: dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate dCTP for DNA synthesis. Since dFdCDP reduces the levels of dCTP, there is less competition for gemcitabine triphosphate for incorporation into DNA.,Gemcitabine can also reduce metabolism and elimination of active metabolites from the target cel, prolonging high intracellular concentrations of the active metabolites. Such self-potentiating effects are not present withcytarabine.TargetActionsOrganismADNAcross-linking/alkylationHumansARibonucleoside-diphosphate reductase large subunitinhibitorHumansUThymidylate synthaseinhibitorHumansUUMP-CMP kinaseinhibitorHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cytidine Deaminase Substrates', 'Deoxycytidine', 'Deoxyribonucleosides', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Pyrimidine Analogues', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Ribonucleosides', 'Ribonucleotide Reductases, antagonists & inhibitors', 'Toxic Actions']" +DB00762,Irinotecan,Irinotecanis an antineoplastic enzyme inhibitor used to treat metastatic carcinoma of the colon or rectum.,"['Q969P6', 'P11387']","Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).",CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=CC=C(OC(=O)N3CCC(CC3)N3CCCCC3)C=C12,"Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.TargetActionsOrganismADNA topoisomerase I, mitochondrialinhibitorHumansADNA topoisomerase inhibitorHumans",[],"['Alkaloids', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Carbohydrates', 'Cholinesterase substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Disaccharides', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'Oligosaccharides', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Pharmaceutical Preparations', 'Polysaccharides', 'Topoisomerase 1 (TOP1) inhibitors', 'Topoisomerase I Inhibitors', 'Topoisomerase Inhibitors', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index', 'UGT1A9 Substrates', 'UGT1A9 Substrates with a Narrow Therapeutic Index']" +DB06825,Triptorelin,Triptorelinis a GnRH agonist indicated for the palliative treatment of advanced prostate cancer.,['P30968'],"The first administration of triptorelin is followed by a transient surge of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol,and testosterone. The time, peak and decline of testosterone in the body varies depending on the dose administered. This initial surge is often responsible for worsening of prostate cancer symptoms such as urethral or bladder outlet obstruction, bone pain, spinal cord injury and hematuria in the early stages. A sustained decrease in FSH and LH, and significant reduction of testicular steroidogenesis is usually seen 2-4 weeks post-initiation of therapy. This result is a reduction of serum testosterone to levels which are typically seen in surgically castrated men. Ultimately, tissues and functions that require these hormones become inactive. The effects of triptorelin can usually be reversed once the drug is discontinued.",CC(C)C[C@H](NC(=O)[C@@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)NCC(N)=O,"Triptorelin is a synthetic agonist analog of gonadotropin releasing hormone (GnRH). Animal studies comparing triptorelin to native GnRH found that triptorelin had fold higher releasing activity for luteinizing hormone, and -fold higher releasing activity for follicle-stimulating hormone.TargetActionsOrganismAGonadotropin-releasing hormone receptoragonistHumans",['Controlled ovarian hyperstimulation therapy'],"['Adrenal Cortex Hormones', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Contraceptive Agents, Hormonal', 'Endocrine Therapy', 'Gonadotropin Releasing Hormone Receptor Agonist', 'Gonadotropin Releasing Hormone Receptor Agonists', 'Gonadotropin-releasing hormone agonist', 'Hormones', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Hypothalamic Hormones', 'Luteolytic Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary Hormone-Releasing Hormones', 'Potential QTc-Prolonging Agents', 'Proteins', 'QTc Prolonging Agents', 'Reproductive Control Agents']" +DB00257,Clotrimazole,Clotrimazoleis a topical broad-spectrum antifungal agent used for the treatment of a wide variety of dermatophyte infections and candidiasis.,"['P10613', 'O15554', 'O75469', 'Q8TDS4']","Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidalin vitroagainst Candida albicans and other species of the genus Candida at higher concentrationsLabel. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations2.Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations2.",ClC1=CC=CC=C1C(N1C=CN=C1)(C1=CC=CC=C1)C1=CC=CC=C1,"Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane,. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth.Though decreased ergosterol, due to the inhibition of lanosterol -demethylase (also known asCYP)is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities.TargetActionsOrganismACytochrome P antagonistinhibitorYeastAIntermediate conductance calcium-activated potassium channel protein inhibitorHumansAErgosterolinhibitorCandida albicansUNuclear receptor subfamily group I member activatorHumansUHydroxycarboxylic acid receptor partial agonistHumans",[],"['Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Antifungal Agents', 'Antifungal Agents (Vaginal)', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Azole Antifungals', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strong)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (strong)', 'Cytochrome P-450 CYP3A7 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Gynecological Antiinfectives and Antiseptics', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazole and Triazole Derivatives', 'Imidazole Derivatives', 'Imidazoles', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 inducers', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Steroid Synthesis Inhibitors', 'Stomatological Preparations']" +DB00183,Pentagastrin,"Pentagastrinis a gastrin-like molecule used as a diagnostic aid for the evaluation of gastric acid secretory function, gastric hypersecretion, and Zollinger-Ellison tumors.",['P32239'],"Pentagastrin is indicated as a diagnostic aid for evaluation of gastric acid secretory function. It is effective in testing for anacidity (achlorhydria) in patients with suspected pernicious anemia, atrophic gastritis, or gastric carcinoma. It is also effective in determining the reduction in acid output after operations for peptic ulcer, such as vagotomy or gastric resection.",CSCC[C@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CCNC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(N)=O,"The exact mechanism by which pentagastrin stimulates gastric acid, pepsin, and intrinsic factor secretion is unknown; however, since pentagastrin is an analogue of natural gastrin, it is believed that it excites the oxyntic cells of the stomach to secrete to their maximum capacity. Pentagastrin stimulates pancreatic secretion, especially when administered in large intramuscular doses. Pentagastrin also increases gastrointestinal motility by a direct effect on the intestinal smooth muscle. However, it delays gastric emptying time probably by stimulation of terminal antral contractions, which enhance retropulsion.TargetActionsOrganismAGastrin/cholecystokinin type B receptoragonistHumans",[],"['Amino Acids, Peptides, and Proteins', 'Diagnostic Agents', 'Gastrins', 'Gastrointestinal Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Oligopeptides', 'Pentagastrin, antagonists & inhibitors', 'Peptides', 'Proteins', 'Tests for Gastric Secretion']" +DB00276,Amsacrine,Amsacrineis a cytotoxic agent used to induce remission in acute adult leukemia that is not adequately responsive to other agents.,"['P11388', 'Q12809', 'P02763', 'P02768']","Amsacrine is an aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects.",COC1=C(NC2=C3C=CC=CC3=NC3=CC=CC=C23)C=CC(NS(C)(=O)=O)=C1,Amsacrine binds to DNA through intercalation and external binding. It has a base specificity for A-T pairs. Rapidly dividing cells are two to four times more sensitive to amsacrine than are resting cells. Amsacrine appears to cleave DNA by inducing double stranded breaks. Amsacrine also targets and inhibits topoisomerase II. Cytotoxicity is greatest during the S phase of the cell cycle when topoisomerase levels are at a maximum.TargetActionsOrganismADNAintercalationHumansADNA topoisomerase -alphainhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUAlpha--acid glycoprotein Not AvailableHumansUSerum albuminNot AvailableHumans,[],"['Acridines', 'Aminoacridines', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cardiotoxic antineoplastic agents', 'Compounds used in a research, industrial, or household setting', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Indicators and Reagents', 'Intercalating Agents', 'Laboratory Chemicals', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors']" +DB01030,Topotecan,"Topotecanis an antineoplastic agent used to treat ovarian cancer, small cell lung cancer, or cervical cancer.","['P11387', 'Q969P6']","Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from theCamptotheca acuminatatree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.",CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=O,"Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death).Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−) and downstream (+) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor.TargetActionsOrganismADNA topoisomerase inhibitorHumansADNAintercalationHumansUDNA topoisomerase I, mitochondrialinhibitorHumans",[],"['Alkaloids', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 1 Substrates with a Narrow Therapeutic Index', 'MATE 2 Substrates', 'MATE 2 Substrates with a Narrow Therapeutic Index', 'MATE inhibitors', 'MATE substrates', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Topoisomerase 1 (TOP1) inhibitors', 'Topoisomerase I Inhibitors', 'Topoisomerase Inhibitors']" +DB01708,Prasterone,Prasteroneis a steroid formulated as a vaginal insert indicated for the treatment of moderate to severe dyspareunia associated with menopausal vulvar and vaginal atrophy.,"['P03372', 'Q92731', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'P10275', 'Q07869', 'Q99720', 'O75469', 'Q14994']","DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. DHEA is increased by exercise and calorie restriction. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.",[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@]([H])(O)CC[C@]12C,"DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, it is argued that there is a role in the immune and stress response. DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia as it is produced nearly entirely by the adrenal glands. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.TargetActionsOrganismUEstrogen receptor alphabinderHumansUEstrogen receptor betaactivatorHumansUGABA(A) ReceptorantagonistHumansUNMDA receptoragonistHumansUAndrogen receptoragonistHumansUPeroxisome proliferator-activated receptor alphaactivatorHumansUSigma non-opioid intracellular receptor agonistHumansUNuclear receptor subfamily group I member activatorHumansUNuclear receptor subfamily group I member activatorHumans",[],"['17-Ketosteroids', 'Adjuvants, Immunologic', 'Adrenal Cortex Hormones', 'Alimentary Tract and Metabolism', 'Anabolic Agents for Systemic Use', 'Anabolic Steroids', 'Androgens and Estrogens', 'Androstan Derivatives', 'Androstanes', 'Androstenes', 'Androstenols', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunologic Factors', 'Ketosteroids', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'OATP2B1/SLCO2B1 substrates', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Testosterone Congeners']" +DB00269,Chlorotrianisene,"A powerful synthetic, non-steroidal estrogen. [PubChem]",['P03372'],"Chlorotrianisene is a nonsteroidal synthetic estrogen. After menopause, when the body no longer produces estrogen, chlorotrianisene is used as a simple replacement of estrogen. The estrogen-stimulated endometrium may bleed within 48-72 hours after discontinuance of estrogen therapy. Paradoxically, prolonged estrogen therapy may cause shrinkage of the endometrium and an increase in size of the myometrium. Estrogens have a weak anabolic effect and may cause sodium retention with associated fluid retention and edema. Estrogens may also decrease elevated blood cholesterol and phospholipid concentrations. Estrogens affect bone by increasing calcium deposition and accelerating epiphyseal closure, following initial growth stimulation. During the preovulatory or nonovulatory phase of the menstrual cycle, estrogen is the principal determinant in the onset of menstruation. A decline of estrogenic activity at the end of the menstrual cycle also may induce menstruation; however, the cessation of progesterone secretion is the most important factor during the mature ovulatory phase of the menstrual cycle. The benefit derived from estrogen therapy in the prevention of postpartum breast engorgement must be carefully weighed against the potential increased risk of puerperal thromboembolism associated with the use of large doses of estrogens.",COC1=CC=C(C=C1)C(Cl)=C(C1=CC=C(OC)C=C1)C1=CC=C(OC)C=C1,"Chlorotrianisene binds to the estrogen receptor on various estrogen receptor bearing cells. Target cells include cells in the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.TargetActionsOrganismAEstrogen receptor alphaagonistHumans",[],"['Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Benzene Derivatives', 'Benzylidene Compounds', 'Estrogens', 'Estrogens, Non-Steroidal', 'Genito Urinary System and Sex Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Natural and Semisynthetic Estrogens, Plain', 'Sex Hormones and Modulators of the Genital System', 'Stilbenes']" +DB00357,Aminoglutethimide,Aminoglutethimideis an adrenocortical steroid synthesis inhibitor used in the treatment of Cushing's syndrome.,"['P05108', 'P11511']","Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.",CCC1(CCC(=O)NC1=O)C1=CC=C(N)C=C1,"Aminoglutethimide reduces the production of D-pregnenolone and blocks several other steps in steroid synthesis, including the C-, C-, and C- hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P- complexes. Specifically, the drug binds to and inhibits aromatase which is essential for the generation of estrogens from androstenedione and testosterone. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.TargetActionsOrganismACholesterol side-chain cleavage enzyme, mitochondrialinhibitorHumansACytochrome P AinhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Aromatase Inhibitors', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Endocrine Therapy', 'Enzyme Inhibitors', 'Estrogen Antagonists', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Narrow Therapeutic Index Drugs', 'Piperidines', 'Piperidones', 'Steroid Synthesis Inhibitors']" +DB00712,Flurbiprofen,Flurbiprofenis an NSAID used to treat the signs and symptoms of osteoarthritis and rheumatoid arthritis.,"['P35354', 'P23219']","Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of the propionic acid class, is structually and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen, and has similar pharmacological actions to other prototypica NSAIAs. Flurbiprofen exhibits antiinflammatory, analgesic, and antipyretic activities. The commercially available flurbiprofen is a racemic mixture of (+)S- and (-) R-enantiomers. The S-enantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity.",CC(C(O)=O)C1=CC(F)=C(C=C1)C1=CC=CC=C1,"Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G (PGG) and PGG to prostaglandin H (PGH) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX- and -. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Acyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Benzene Derivatives', 'Biphenyl Compounds', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'Ophthalmologicals', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Propionates', 'Sensory Organs', 'Sensory System Agents', 'Throat Preparations', 'Topical Products for Joint and Muscular Pain', 'UGT1A1 Inhibitors', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB04630,Aldosterone,A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.,"['P04150', 'P08235']","At the late distal tubule and collecting duct, aldosterone has two main actions: 1) aldosterone acts on mineralocorticoid receptors (MR) on principal cells in the distal tubule of the kidney nephron, increasing the permeability of their apical (luminal) membrane to potassium and sodium and activates their basolateral Na+/K+ pumps, stimulating ATP hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, hence reabsorbing sodium (Na+) ions and water into the blood, and secreting potassium (K+) ions into the urine; 2) aldosterone stimulates H+ secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate (HCO3−) levels and its acid/base balance; and 3) aldosterone may act on the central nervous system via the posterior pituitary gland to release vasopressin (ADH) which serves to conserve water by direct actions on renal tubular resorption.",[H][C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CC[C@]4(C)[C@@]3([H])[C@@H](O)C[C@]12C=O)C(=O)CO,TargetActionsOrganismUGlucocorticoid receptorNot AvailableHumansUMineralocorticoid receptoragonistHumans,[],"['11-Hydroxycorticosteroids', 'Adrenal Cortex Hormones', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydroxycorticosteroids', 'Immunosuppressive Agents', 'Mineralocorticoids', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB00842,Oxazepam,"Oxazepamis an intermediate-acting benzodiazepine with slow onset commonly used to treat panic disorders, severe anxiety, alcohol withdrawals, and insomnia.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Benzodiazepines, including oxazepam, exert their sedative and anxiolytic effects by potentiating the effects of endogenous GABA, the primary inhibitory neurotransmitter in the CNS.10Compared to other benzodiazepines, it has relatively low potency and a moderate duration of action.10Oxazepam should be administered with caution to patients for whom a drop in blood pressure may lead to cardiac complications as, in rare cases, it may cause hypotension.14",OC1N=C(C2=CC=CC=C2)C2=C(NC1=O)C=CC(Cl)=C2,"Like other benzodiazepines, oxazepam exerts its anxiolytic effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA(A) receptors, the main inhibitory neurotransmitter receptors in the mammalian brain.GABA(A) receptors are a component of GABA-gated ionotropic chloride channels that produce inhibitory postsynaptic potentials - following activation by GABA, the channel undergoes a conformational change that allows the passage of chloride ions through the channel. The inhibitory potentials produced by GABA neurotransmission play an integral role in the suppression and control of epileptiform nerve firing such as that seen in epilepsy, which makes the GABA system a desirable target in the treatment of epilepsy.Benzodiazepines are positive allosteric modulators of GABA(A) function. They bind to the interface between alpha (α) and gamma (γ) subunits on the receptor, commonly referred to as the benzodiazepine binding site, and modulate the receptor such that its inhibitory response to GABA binding is dramatically increased.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB00927,Famotidine,"Famotidineis a histamine H2 receptor antagonist used to treat duodenal ulcers, benign gastric ulcers, GERD, and Zollinger-Ellison syndrome.",['P25021'],"Famotidine decreases the production of gastric acid, suppresses acid concentration and pepsin content, and decreases the volume of gastric secretion. Famotidine inhibits both basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, caffeine, insulin, and pentagastrin.5,6Famotidine has a dose-dependent therapeutic action, with the highest dose having the most extended duration of action and the highest inhibitory effect on gastric acid secretion. Following oral administration, the onset of action is within one hour, and the peak effect is reached within 1-3 hours. The duration of effect is about 10-12 hours.1",NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1,"Histamine acts as a local hormone that stimulates the acid output by parietal cells via a paracrine mechanism. Neuroendocrine cells called enterochromaffin-like (ECL) cells lie close to the parietal cells and regulate the basal secretion of histamine. Histamine release is also promoted from stimulation by acetylcholine and gastrin, a peptide hormone. Gastrin (G) cells release gastrin, which works on CCKreceptors on ECL cells. This action promotes the release of histamine from ECL cells. Upon release, histamine acts on Hreceptors expressed on the basolateral membrane of parietal cells, leading to increased intracellular cAMP levels and activated proton pumps on parietal cells. Proton pump releases more protons into the stomach, thereby increasing the secretion of acid.In conditions that are associated with acid hypersecretion such as ulcers, there is a loss of regulation of acid secretion. Famotidine works on Hreceptors and blocks the actions of histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Acid Reducers', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H2 Antagonists', 'MATE 1 Inhibitors', 'MATE inhibitors', 'Neurotransmitter Agents', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OCT2 Inhibitors', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfur Compounds', 'Thiazoles']" +DB04930,Permethrin,Permethrinis an insecticide used to prevent infestation with Sarcoptes scabiei (scabies).,"['P35498', 'P03372', 'O75469']","Permethrin, a pyrethroid, is active against a broad range of pests including lice, ticks, fleas, mites, and other arthropods.",CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC(OC2=CC=CC=C2)=CC=C1,Permethrin acts on the nerve cell membrane to disrupt the sodium channel current by which the polarization of the membrane is regulated. Delayed repolarization and paralysis of the pests are the consequences of this disturbance.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUEstrogen receptor alphaNot AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumans,[],"['Agrochemicals', 'Antiparasitic Products, Insecticides and Repellents', 'Benzene Derivatives', 'Compounds used in a research, industrial, or household setting', 'Cyclopentane Monoterpenes', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Ectoparasiticides, Incl. Scabicides', 'Ectoparasiticides, Incl. Scabicides, Insecticides and Repellents', 'Enzyme Inhibitors', 'Ethers', 'Insecticides', 'Monoterpenes', 'Pesticides', 'Phenols', 'Phenyl Ethers', 'Pyrethrines, Incl. Synthetic Compounds', 'Pyrethrins', 'Scabicides and Pediculicides', 'Terpenes', 'Toxic Actions']" +DB00753,Isoflurane,Isofluraneis an inhaled general anesthetic used in surgery.,"['P14867', 'P98194', 'P23415', 'P42261', 'Q09470', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P30049', 'P0DP23', 'P43681', 'P17787']",Isoflurane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.,FC(F)OC(Cl)C(F)(F)F,"Isoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Isoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. Also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Isoflurane also binds to the GABA receptor, the large conductance Ca+activated potassium channel, the glutamate receptor and the glycine receptor.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansACalcium-transporting ATPase type C member inhibitorHumansAGlycine receptor subunit alpha-agonistHumansAGlutamate receptor antagonistHumansAPotassium voltage-gated channel subfamily A member inducerHumansAGABA(A) Receptorpositive allosteric modulatorHumansUATP synthase subunit delta, mitochondrialunknownHumansUCalmodulinother/unknownHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit beta-antagonistHumans",['Induction and Maintenance of General Anesthesia'],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Inhalation', 'Anticholinergic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Ethers', 'Hydrocarbons, Halogenated', 'Hypotensive Agents', 'Methyl Ethers', 'Nervous System', 'Nicotinic Antagonists', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00175,Pravastatin,"Pravastatinis an HMG-CoA reductase inhibitor used to lower lipid levels and to reduce the risk of cardiovascular events, including myocardial infarction and stroke.","['P04035', 'Q92769']","The action of pravastatin on the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase produces an increase in the expression of hepatic LDL receptors which in order decreases the plasma levels of LDL cholesterol.10The effect of pravastatin has been shown to significantly reduce the circulating total cholesterol, LDL cholesterol, and apolipoprotein B. As well, it modestly reduces very low-density-lipoproteins (VLDL) cholesterol and triglycerides while increasing the level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A.17In clinical trials with patients with a history of myocardial infarction or angina with high total cholesterol, pravastatin decreased the level of total cholesterol by 18%, decreased of LDL by 27%, decreased of triglycerides by 6% and increased of high-density lipoprotein (HDL) by 4%. As well, there was reported a decrease in risk of death due to coronary disease of 24%.1When coadministered withcholestyramine, pravastatin can reduce by 50% the levels of LDL and slow the progression of atherosclerosis and the risk of myocardial infarction and death.10",[H][C@]12[C@H](C[C@H](O)C=C1C=C[C@H](C)[C@@H]2CC[C@@H](O)C[C@@H](O)CC(O)=O)OC(=O)[C@@H](C)CC,"Pravastatin is a specific inhibitor of the hepatic HMG-CoA reductase in humans.The inhibition of this enzyme produces a reduction in cholesterol biosynthesis as HMG-CoA reductase activity is an early-limiting step in cholesterol biosynthesis.The inhibitory mechanism of action produces a reduction in cholesterol synthesis which in order has been observed to increase the number of LDL receptors on cell surfaces and an enhancement in receptor-mediated metabolism of LDL and clearance.On the other hand, pravastatin-driven inhibition of LDL production inhibits hepatic synthesis of VLDL as the LDL is the precursor for these molecules.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUHistone deacetylase inhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Noxae', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'OATP2B1/SLCO2B1 substrates', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Toxic Actions']" +DB00995,Auranofin,"Auranofinis an antirheumatic used to treat active, progressive, or destructive forms of inflammatory arthritis.","['P30044', 'O14920']",Auranofin is a gold salt used in treating inflammatory arthritis. Gold salts are called second-line drugs because they are often considered when the arthritis progresses in spite of antiinflammatory drugs (NSAIDs and corticosteroids).,CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O,"Inflammatory arthritis can cause joint swelling, warmth, pain, and tenderness; one cause of this condition is rheumatoid arthritis.In patients with rheumatoid arthritis, gold salts such as auranofin can be administered to decrease joint inflammation and prevent the destruction of bones and cartilage. Though the mechanism of action of auranofin is not fully established in rheumatoid arthritis, this drug has been shown to inhibit phagocytosis and the release of antibodies and enzymes that play a role in cytotoxic reactions, suppressing the inflammatory response.,Aside from its probable immune effects in inflammatory arthritis, studies have shown that auranofin inhibits thioredoxin reductase. This enzyme has various roles in cell homeostasis, including the regulation of free radicals.,Thioredoxin reductase can be over expressed in various types of tumours, rendering it an attractive target for anticancer drug development.Studies have shown that inhibiting thioredoxin reductase can cause oxidative stress and apoptosis of tumour cells by increasing the formation of free radicals. Aurofin's thiol ligand binds with high affinity to thiol and selenol groups, forming irreversible reaction products.One study showed that treatment with auranofin increased the production or reactive oxygen species and caused elevation of intracellular calcium concentration in platelets, leading to cell death.Another study showed that auranofin enhanced the production of free radicals, governing T-cell activation.TargetActionsOrganismAPeroxiredoxin-, mitochondrialinhibitorHumansAInhibitor of nuclear factor kappa-B kinase subunit betainhibitorHumans",[],"['Antiinflammatory and Antirheumatic Products', 'Antirheumatic Agents', 'Drugs that are Mainly Renally Excreted', 'Gold Compounds', 'Gold Preparations', 'Musculo-Skeletal System', 'Organogold Compounds', 'Organometallic Compounds', 'Specific Antirheumatic Agents']" +DB00855,Aminolevulinic acid,"Aminolevulinic acidis a porphyrin precursor used to treat actinic keratosis of the face, scalp, and upper extremities, as well as to visualize a glioma.",['P13716'],"The metabolism of aminolevulinic acid (ALA) is the first step in the biochemical pathway resulting in heme synthesis. Aminolevulinic acid is not a photosensitizer, but rather a metabolic precursor of protoporphyrin IX (PpIX), which is a photosensitizer. The synthesis of ALA is normally tightly controlled by feedback inhibition of the enzyme, ALA synthetase, presumably by intracellular heme levels. ALA, when provided to the cell, bypasses this control point and results in the accumulation of PpIX, which is converted into heme by ferrochelatase through the addition of iron to the PpIX nucleus.",NCC(=O)CCC(O)=O,"According to the presumed mechanism of action, photosensitization following application of aminolevulinic acid (ALA) topical solution occurs through the metabolic conversion of ALA to protoporphyrin IX (PpIX), which accumulates in the skin to which aminolevulinic acid has been applied. When exposed to light of appropriate wavelength and energy, the accumulated PpIX produces a photodynamic reaction, a cytotoxic process dependent upon the simultaneous presence of light and oxygen. The absorption of light results in an excited state of the porphyrin molecule, and subsequent spin transfer from PpIX to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals. Photosensitization of actinic (solar) keratosis lesions using aminolevulinic acid, plus illumination with the BLU-UTM Blue Light Photodynamic Therapy Illuminator (BLU-U), is the basis for aminolevulinic acid photodynamic therapy (PDT).TargetActionsOrganismADelta-aminolevulinic acid dehydrataseinducerHumans",[],"['Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Dermatologicals', 'Enkephalins', 'Keto Acids', 'Levulinic Acids', 'Misc. Skin and Mucous Membrane Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Opioid Peptides', 'Optical Imaging Agent', 'Peptides', 'Photosensitizing Agents', 'Photosensitizing Agents for Phototherapy', 'Porphyrin Precursor', 'Proteins', 'Radiation-Sensitizing Agents', 'Roentgenography', 'Sensitizers Used in Photodynamic/radiation Therapy']" +DB01165,Ofloxacin,"Ofloxacinis an antibacterial agent used for the treatment of bacterial infections in many parts of the body, including the respiratory tract, kidney, skin, soft tissue, and urinary tract.","['P43700', 'P43702', 'P11388']","Ofloxacin is a quinolone/fluoroquinolone antibiotic. Ofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.",CC1COC2=C3N1C=C(C(O)=O)C(=O)C3=CC(F)=C2N1CCN(C)CC1,"Ofloxacin acts on DNA gyrase and toposiomerase IV, enzymes which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. By inhibiting their function, the drug thereby inhibits normal cell division.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'OAT1/SLC22A6 inhibitors', 'Ophthalmologicals', 'Otologicals', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Sensory Organs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00955,Netilmicin,Netilmicinis an aminoglycoside used to treat a wide variety of infections in the body.,['P0A7S3'],"Netilmicin is a semisynthetic, water soluble antibiotic of the aminoglycoside group, produced by the fermentation of Micromonospora inyoensis, a species of actinomycete. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. It is active at low concentrations against a wide variety of pathogenic bacteria includingEscherichia coli, bacteria of theKlebsiella-Enterobacter-Serratiagroup,Citrobactersp.,Proteussp. (indole-positive and indole-negative), includingProteus mirabilis,P. morganii, P. rettgrei, P. vulgaris, Pseudomonas aeruginosaandNeisseria gonorrhoea. Netilmicin is also activein vitroagainst isolates ofHemophilus influenzae, Salmonellasp.,Shigellasp. and against penicillinase and non-penicillinase-producingStaphylococcusincluding methicillin-resistant strains. Some strains ofProvidenciasp.,Acinetobactersp. andAeromonassp. are also sensitive to netilmicin. Many strains of the above organisms which are found to be resistant to other aminoglycosides, such as kanamycin, gentamicin, tobramycin and sisomicin, are susceptible to netilmicinin vitro. Occasionally, strains have been identified which are resistant to amikacin but susceptible to netilmicin. The combination of netilmicin and penicillin G has a synergistic bactericidal effect against most strains ofStreptococcus faecalis(enterococcus). The combined effect of netilmicin and carbenicillin or ticarcillin is synergistic for many strains ofPseudomonas aeruginosa. In addition, many isolates ofSerratia, which are resistant to multiple antibiotics, are inhibited by synergistic combinations of netilmicin with carbenicillin, azlocillin, mezlocillin, cefamandole, cefotaxime or moxalactam. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.",CCN[C@@H]1C[C@H](N)[C@@H](O[C@H]2OC(CN)=CC[C@H]2N)[C@H](O)[C@H]1O[C@H]1OC[C@](C)(O)[C@H](NC)[C@H]1O,"Aminoglycosides like netilmicin ""irreversibly"" bind to specific S-subunit proteins and S rRNA. Specifically netilmicin binds to four nucleotides of S rRNA and a single amino acid of protein S. This interferes with decoding site in the vicinity of nucleotide in S rRNA of S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes, leaving the bacterium unable to synthesize proteins vital to its growth.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal RNAinhibitorEnteric bacteria and other eubacteria",[],"['Agents that produce neuromuscular block (indirect)', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Carbohydrates', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inhibitors', 'Gentamicins', 'Glycosides', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents', 'Ophthalmologicals', 'Protein Synthesis Inhibitors', 'Sensory Organs']" +DB01032,Probenecid,"Probenecidis a medication used to treat gouty arthritis, tophaceous gout, and hyperuricemia.","['Q4U2R8', 'Q9NSA0', 'Q8TCC7', 'Q96RD7', 'Q9NYV7']","Probenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the reabsorption of urate at the proximal convoluted tubule, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. At the proximal and distal tubles, probenecid competitively inhibits the secretion of many weak organic acids including penicillins, most cephalosporins, and some other β-lactam antibiotics. This results in an increase in the plasma concentrations of acidic drugs eliminated principally by renal secretion, but only a slight increase if the drug is eliminated mainly by filtration. Thus, the drug can be used for therapeutic advantages to increase concentrations of certain β-lactam antibiotics in the treatment of gonorrhea, neurosyphilis, or pelvic inflammatory disease (PID).",CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(O)=O,"Probenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Probenecid may also reduce plasma binding of urate and inhibit renal secretion of uric acid at subtherapeutic concentrations. The mechanism by which probenecid inhibits renal tubular transport is not known, but the drug may inhibit transport enzymes that require a source of high energy phosphate bonds and/or nonspecifically interfere with substrate access to protein receptor sites on the kidney tubules.TargetActionsOrganismASolute carrier family member inhibitorHumansASolute carrier family member inhibitorHumansASolute carrier family member inhibitorHumansUPannexin-antagonistHumansUTaste receptor type member Not AvailableHumans",[],"['Adjuvants, Pharmaceutic', 'Amides', 'Antigout Preparations', 'Antirheumatic Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Musculo-Skeletal System', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Pharmaceutic Aids', 'Pharmaceutical Preparations', 'Preparations Increasing Uric Acid Excretion', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'UGT1A1 Inhibitors', 'Uricosuric Agents']" +DB00648,Mitotane,Mitotaneis an adrenal cortex inhibitor used to treat adrenocortical tumors and Cushing's syndrome.,"['P15538', 'P03372', 'P06401', 'P10275', 'P10109']","Mitotane is an oral chemotherapeutic agent indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. The administration of Mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-B-hydroxyl cortisol.",ClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl,"Its biochemical mechanism of action is unknown, although data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex.TargetActionsOrganismACytochrome P B, mitochondrialinducerHumansUEstrogen receptor alphaNot AvailableHumansUProgesterone receptorNot AvailableHumansUAndrogen receptorantagonistHumansUAdrenodoxin, mitochondrialunknownHumans",[],"['Adrenal Cytotoxic Agents', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 Enzyme Inducers', 'Hydrocarbons, Chlorinated', 'Hydrocarbons, Halogenated', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'Thyroxine-binding globulin inducers']" +DB00412,Rosiglitazone,Rosiglitazoneis a thiazolidinedione indicated as an adjunct to diet and exercise to maintain glycemic control in type 2 diabetes.,"['P37231', 'O60488', 'Q07869', 'Q03181', 'P19793', 'P28702', 'P48443']","When rosiglitazone is used as monotherapy, it is associated with increases in total cholesterol, LDL, and HDL. It is also associated with decreases in free fatty acids. Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL ratio peaked after 2 months of therapy and then appeared to decrease over time.",CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C1=CC=CC=N1,"Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin.TargetActionsOrganismAPeroxisome proliferator-activated receptor gammaagonistHumansULong-chain-fatty-acid--CoA ligase inhibitorHumansUPeroxisome proliferator-activated receptor alphaNot AvailableHumansUPeroxisome proliferator-activated receptor deltaNot AvailableHumansURetinoic acid receptor RXR-alphaNot AvailableHumansURetinoic acid receptor RXR-betaNot AvailableHumansURetinoic acid receptor RXR-gammaNot AvailableHumans",[],"['Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Hypoglycemia-Associated Agents', 'NTCP Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'Oral Hypoglycemics', 'Peroxisome Proliferator Receptor gamma Agonist', 'Peroxisome Proliferator-activated Receptor Activity', 'Sulfur Compounds', 'Thiazoles', 'Thiazolidinediones', 'Vasodilating Agents']" +DB08907,Canagliflozin,Canagliflozinis a sodium-glucose co-transporter 2 (SGLT2) inhibitor used to manage hyperglycemia in type 2 diabetes mellitus (DM). Also used to reduce the risk of major cardiovascular events in patients with established cardiovascular disease and type 2 DM.,['P31639'],"This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent mannerLabel. The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine2,7. The end result of canagliflozin administration is increased urinary excretion of glucose and less renal absorption of glucose, decreasing glucose concentration in the blood and improving glycemic control.A note on type 2 diabetes and cardiovascular diseaseThe risk of cardiovascular events in diabetes type 2 is increased due to the damaging effects of diabetes on blood vessels and nerves in the cardiovascular system. In particular, there is a tendency for hyperglycemia to create pro-atherogenic (plaque forming) lesions in blood vessels, leading to various fatal and non-fatal events including stroke and myocardial infarction5,9. Long-term glycemic control has been proven to be effective in the prevention of cardiovascular events such as myocardial infarction and stroke in patients with type 2 diabetes6.",[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1,"The sodium-glucose co-transporter (SGLT), is found in the proximal tubules of the kidney, and reabsorbs filtered glucose from the renal tubular lumen. Canagliflozin inhibits the SGLT co-transporter. This inhibition leads to lower reabsorption of filtered glucose into the body and decreases the renal threshold for glucose (RTG), leading to increased glucose excretion in the urineLabel.TargetActionsOrganismASodium/glucose cotransporter inhibitorHumans",[],"['Agents causing hyperkalemia', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Diuretics', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Glucosides', 'Hypotensive Agents', 'Oral Hypoglycemics', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors', 'Sulfur Compounds', 'Thiophenes', 'UGT1A9 Substrates']" +DB00169,Vitamin D3,"Vitamin D3is a form of Vitamin D used in the treatment of specific medical conditions such as refractory rickets, hypoparathyroidism, and familial hypophosphatemia, as well as osteoporosis and chronic kidney disease.",['P11473'],"The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D12,13,14. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization12,13,14. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules12,13,14. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys12,13,14. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys12,13,14.",CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C,"Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D precursor -dehydrocholesterol in the skin via exposure to sunlight,,,.Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions.Ordinarily, while vitamin D is made naturally via photochemical processes in the skin, both itself and vitamin D can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. At the liver, vitamin D or D is hydroxylated to -hydroxyvitamin D and then finally to the primary active metabolite ,-dihydroxyvitamin D in the kidney via further hydroxylation,. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma,.In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about -% to -% and % increased to %, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys.Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as to genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD+ T cells, amongst a variety of other proposed actions.TargetActionsOrganismAVitamin D receptoragonistHumans","['Calcium supplementation', 'Nutritional supplementation', 'Vitamin D Supplementation', 'Vitamin supplementation']","['Alimentary Tract and Metabolism', 'Bone Density Conservation Agents', 'Calcium-Regulating Hormones and Agents', 'Cholecalciferol, antagonists & inhibitors', 'Cholestanes', 'Cholestenes', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diet, Food, and Nutrition', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Food', 'Fused-Ring Compounds', 'Growth Substances', 'Lipids', 'Membrane Lipids', 'Micronutrients', 'Musculo-Skeletal System', 'Physiological Phenomena', 'Secosteroids', 'Steroids', 'Sterols', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00371,Meprobamate,Meprobamateis an anxiolytic drug used for the short-term management of anxiety symptoms.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445']","Meprobamate is an anxiolytic drug. It was the best selling minor tranquilizer for a time but has largely been replaced by benzodiazepines. Meprobamate has most of the pharmacological effects and dangers of the barbiturates (though it was marketed as being safer) but it is less sedating at effective doses. Meprobamate exhibits some anticonvulsant effects in absence seizures; however, it is reported to potentially exacerbate generalized tonic-clonic seizures. It has also been used as a hypnotic (sleeping pill). However, its is currently only licensed as an anxiolytic and it is a third or fourth-order choice.",CCCC(C)(COC(N)=O)COC(N)=O,"Meprobamate's mechanism of action is not fully understood; in animal studies, meprobamate is reported to act at multiple sites in the central nervous system, such as the thalamus and limbic system. It binds to the GABAAreceptors, leading to inhibitory effects on the neurons transmitting signals in the reticular formation and spinal cord. Consequently, effects such as sedation and altered perception of pain are observed.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumans",[],"['Acids, Acyclic', 'Anti-Anxiety Agents', 'Carbamates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Peripheral Nervous System Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00351,Megestrol acetate,Megestrol acetateis a progestin that is administered orally to treat anorexia and cachexia or serious unexplained weight loss and is also used as an antineoplastic agent to treat certain types of malignancy.,"['P06401', 'P04150']","Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967.",[H][C@@]12CC[C@](OC(C)=O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=C(C)C2=CC(=O)CC[C@]12C,"The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes.TargetActionsOrganismAProgesterone receptoragonistHumansUGlucocorticoid receptoragonistHumans",['Palliative Treatment'],"['Adrenal Cortex Hormones', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Appetite Stimulants', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Contraceptives, Oral, Synthetic', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones and Related Agents', 'Hyperglycemia-Associated Agents', 'Megestrol', 'P-glycoprotein inhibitors', 'Pregnadien Derivatives', 'Pregnadienes', 'Pregnanes', 'Progestin Contraceptives', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00334,Olanzapine,"Olanzapineis an antipsychotic drug used in the management of schizophrenia, bipolar 1 disorder, and agitation associated with these disorders.","['P28223', 'P14416', 'P21728', 'P21918', 'P35462', 'P21917', 'P28335', 'P46098', 'P50406', 'P35367', 'P35348', 'P35368', 'P11229', 'P08172', 'P20309', 'P08173', 'P21728', 'P21918', 'P08588', 'P07550', 'P13945', 'P08908', 'P28222', 'P28221', 'P28566', 'P30939', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention.6Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects.10Clinical trials for the original use of olanzapine demonstrated significant effectiveness in the treatment of schizophrenia and bipolar disorder in adults and acute manic or mixed episodes associated with bipolar disorder in adolescents.4The effect of olanzapine on dopamine and serotonin receptors has been suggested to reduce chemotherapy-induced nausea and vomiting as those receptors are suggested to be involved in this process. For this effect, several clinical trials have been conducted and it has been shown that olanzapine can produce a significant increase in total control of nausea and vomiting.1In a high-level study of the effect of olanzapine for this condition, a complete response on the delay phase was observed in 84% of the individual and control of emesis of over 80% despite the phase.3",CN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2,"The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D, D, D and D in the brain, the serotonin receptors HTA, HTC, HT and HT, the alpha- adrenergic receptor, the histamine receptor H and multiple muscarinic receptors.,As abovementioned, olanzapine presents a wide profile of targets, however, its antagonistic effect towards the dopamine D receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission.On the other hand, olanzapine acts in the serotonin HTA receptors in the frontal cortex in a similar manner than the reported on dopamine D receptors. This determined effect allows for a decrease in adverse effects.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor antagonistHumansUHistamine H receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUD() dopamine receptorantagonistHumansNBeta adrenergic receptorinhibitorHumansU-hydroxytryptamine receptor inhibitorHumansNGABA(A) Receptor Benzodiazepine Binding SiteinhibitorHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Autonomic Agents', 'Benzazepines', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diazepines, Oxazepines, Thiazepines and Oxepines', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H2 Antagonists', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents', 'UGT1A4 substrates']" +DB00623,Fluphenazine,Fluphenazineis a phenothiazine used to treat patients requiring long-term neuroleptic therapy.,"['P14416', 'P21728', 'P0DP23', 'P10275', 'P28223', 'P28335']",Fluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.,OCCN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(C=C3)C(F)(F)F)CC1,"Fluphenazine blocks postsynaptic mesolimbic dopaminergic D and D receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansUCalmodulininhibitorHumansUAndrogen receptorNot AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumansU-hydroxytryptamine receptor CNot AvailableHumans",['Sedation'],"['Agents that reduce seizure threshold', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Delayed-Action Preparations', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Phenothiazines', 'Phenothiazines With Piperazine Structure', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB00656,Trazodone,Trazodoneis a serotonin uptake inhibitor used to treat major depressive disorder.,"['P28223', 'P28335', 'P31645', 'P08908', 'P35367', 'P35348', 'P08913', 'P08909']","Trazodone treats depressed mood and other depression-related symptoms and shows benefit in the treatment of insomnia due to its sedating effects.20It is known to prolong the cardiac QT-interval.21Memory, alertness, and cognition may be decreased by trazodone, especially in elderly patients due to its central nervous system depressant effects.9A note on priapismTrazodone has been associated with the occurrence of priapism, a painful and persistent incidence of penile tissue erection that is unrelievable and can cause permanent neurological damage if left untreated. Patients must be advised to seek immediate medical attention if priapism is suspected.15,21",ClC1=CC=CC(=C1)N1CCN(CCCN2N=C3C=CC=CN3C2=O)CC1,"The mechanism of action of trazodone is not fully understood, however, it is known to inhibit the reuptake of serotonin and block both histamine and alpha--adrenergic receptors.Despite the fact that trazodone is frequently considered a selective serotonin reuptake inhibitor, several reports have shown that other mechanisms including antagonism at serotonin -HTa, -HTc, and -HT receptor subtypes may occur.,The strongest antagonism of trazodone is reported to occur at the serotonin +-HTc receptors, preventing serotonin uptake.In addition to acting on serotonin receptors, trazodone has been shown to inhibit serotonin transporters.,The antidepressant effects of trazodone result from the inhibition of receptor uptake, which normally decreases circulating neurotransmitters, contributing to depressive symptoms.,TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor CagonistHumansASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor Aantagonistpartial agonistHumansUHistamine H receptorantagonistHumansNAlpha-A adrenergic receptorantagonistHumansNAlpha-A adrenergic receptorantagonistHumansU-hydroxytryptamine receptor Cantagonistpartial agonistRat",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anti-Anxiety Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Antidepressive Agents, Triazolopyridine', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'P-glycoprotein inducers', 'Peripheral alpha-1 blockers', 'Piperazines', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Pyridines', 'Pyridones', 'QTc Prolonging Agents', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin antagonist and reuptake inhibitors (SARIs)', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB01104,Sertraline,"Sertralineis a selective serotonin reuptake inhibitor (SSRI) indicated to treat major depressive disorder, social anxiety disorder and many other psychiatric conditions.","['P31645', 'Q01959', 'O00264', 'Q99720', 'P23975', 'Q7RTT9']","Sertraline improves or relieves the symptoms of depression, OCD, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder via the inhibition of serotonin reuptake.10,21Clinical studies have shown that it improves cognition in depressed patients.6It has less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not exert significant anticholinergic, antihistamine, or adrenergic (alpha1, alpha2, beta) blocking activity.5The onset of action and beneficial effects are usually noticed after 4-6 weeks, for reasons that are not fully understood and currently under investigation.17,27",CN[C@H]1CC[C@@H](C2=CC(Cl)=C(Cl)C=C2)C2=CC=CC=C12,"Sertraline selectively inhibits the reuptake of serotonin (-HT) at the presynaptic neuronal membrane, thereby increasing serotonergic activity. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission.,These changes are believed to be responsible for the antidepressant action and beneficial effects in obsessive-compulsive (and other anxiety related disorders). It has been hypothesized that obsessive-compulsive disorder, like depression, is also caused by the disregulation of serotonin.In animal studies, chronic administration of sertraline results in down-regulation of brain norepinephrine receptors.Sertraline displays affinity for sigma- and receptor binding sites, but binds with stronger affinity to sigma- binding sites.In vitro, sertraline shows little to no affinity for GABA, dopaminergic, serotonergic (HTA, HTB, HT), or benzodiazepine receptors.It exerts weak inhibitory actions on the neuronal uptake of norepinephrine and dopamineand exhibits no inhibitory effects on the monoamine oxidase enzyme.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorbinderdownregulatorHumansUSodium-dependent dopamine transporterinhibitorbinderHumansUSigma receptorinhibitorbinderHumansUSodium-dependent noradrenaline transporterinhibitordownregulatorHumansUEquilibrative nucleoside transporter Not AvailableHumans",[],"['Agents that reduce seizure threshold', 'Amines', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Monoamine Oxidase A Substrates', 'Naphthalenes', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01195,Flecainide,Flecainideis a class Ic antiarrhythmic agent used to manage atrial fibrillation and paroxysmal supraventricular tachycardias (PSVT).,"['P35499', 'Q14524', 'Q12809', 'Q92736']","Flecainide inhibits the action of sodium and potassium ion channels in the heart, raising the threshold for depolarization and correcting arrhythmias.10Flecainide has a long duration of action, allowing for once daily dosing.12The therapeutic index is narrow.8Patients should not take this medication if there is already structural heart disease or left ventricular systolic dysfunction.12",FC(F)(F)COC1=CC(C(=O)NCC2CCCCN2)=C(OCC(F)(F)F)C=C1,"Flecainide blocks fast inward sodium channels and slowly unbinds during diastole, prolonging the refractory period of the heart.This blockade also shortens the duration of action potentials through the Purkinjie fibers.Flecainide also prevents delayed rectifier potassium channels from opening, lengthening the action potential through ventricular and atrial muscle fibers.Finally, flecainide also blocks ryanodine receptor opening, reducing calcium release from sarcoplasmic reticulum, which reduces depolarization of cells.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansURyanodine receptor inhibitorHumans",[],"['Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ic', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 1 Substrates with a Narrow Therapeutic Index', 'MATE inhibitors', 'MATE substrates', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Narrow Therapeutic Index Drugs', 'Negative Inotrope', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Piperidines', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB00397,Phenylpropanolamine,"Phenylpropanolamineis a sympathomimetic that was previously used in nasal decongestants and weight loss products, but has been withdrawn by the FDA due to safety risks and lack of efficacy.","['P21728', 'P08588', 'P07550', 'P08913', 'P18089', 'P18825']","Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine.",CC(N)C(O)C1=CC=CC=C1,"Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors, producing tachycardia and a positive inotropic effect.TargetActionsOrganismUDopamine D receptorpartial agonistHumansUBeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUAlpha- adrenergic receptorsNot AvailableHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Obesity Agents', 'Appetite Depressants', 'Autonomic Agents', 'Cardiovascular Agents', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nasal Decongestants', 'Nasal Decongestants for Systemic Use', 'Nasal Preparations', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Propanolamines', 'Propanols', 'Respiratory System Agents', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB01247,Isocarboxazid,Isocarboxazidis a monoamine oxidase inhibitor used to treat enduring and debilitating symptoms of depression following inadequate clinical response to other antidepressant drugs.,"['P21397', 'P27338']","In vivo and in vitro studies demonstrated isocarboxazid-driven inhibition of MAO in the brain, heart, and liver. The reduced MAO activity, caused by isocarboxazid, results in an increased concentration of serotonin, epinephrine, norepinephrine, and dopamine in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The increase of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors like isocarboxazid.1",CC1=CC(=NO1)C(=O)NNCC1=CC=CC=C1,"Isocarboxazid works by irreversibly blocking the action of monoamine oxidases (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B).Isocarboxacid, like other monoamine oxidase inhibitors, are unique psychopharmacological agents whose clinical effect is related to the direct action of the monoamine oxidases to transform them into reactive metabolites.TargetActionsOrganismAAmine oxidase [flavin-containing] AinhibitorHumansAAmine oxidase [flavin-containing] BinhibitorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Isoxazoles', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Monoamine Oxidase Inhibitors, Non-Selective', 'Nervous System', 'Photosensitizing Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB00472,Fluoxetine,"Fluoxetineis a selective serotonin reuptake inhibitor used to treat major depressive disorder, bulimia, OCD, premenstrual dysphoric disorder, panic disorder, and bipolar I.","['P31645', 'P28335', 'Q15822', 'P32297', 'P30926', 'P61024', 'Q12809']","Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas.13However, fluoxetine binds with relatively poor affinity to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors which explains why it has a far more desirable adverse effect profile compared to earlier developed classes of antidepressants such as tricyclic antidepressants.132",CNCCC(OC1=CC=C(C=C1)C(F)(F)F)C1=CC=CC=C1,"The monoaminergic hypothesis of depression emerged in and linked depression with dysfunction of neurotransmitters such as noradrenaline and serotonin.Indeed, low levels of serotonin have been observed in the cerebrospinal fluid of patients diagnosed with depression.As a result of this hypothesis, drugs that modulate levels of serotonin such as fluoxetine were developed.Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and as the name suggests, it exerts it's therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin.As a result, levels of -hydroxytryptamine (-HT) are increased in various parts of the brain.Further, fluoxetine has high affinity for -HT transporters, weak affinity for noradrenaline transporters and no affinity for dopamine transporters indicating that it is -HT selective.Fluoxetine interacts to a degree with the -HTCreceptor and it has been suggested that through this mechanism, it is able to increase noradrenaline and dopamine levels in the prefrontal cortex.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansU-hydroxytryptamine receptor CantagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit beta-antagonistHumansUCyclin-dependent kinases regulatory subunit Not AvailableHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",['Maintenance therapy'],"['Agents that reduce seizure threshold', 'Amines', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Highest Risk QTc-Prolonging Agents', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Nicotinic Antagonists', 'P-glycoprotein inhibitors', 'Propylamines', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Vasodilating Agents']" +DB00857,Terbinafine,Terbinafineis an allylamine antifungal used to treat dermatophyte infections of toenails and fingernails as well as other fungal skin infections.,"['Q92206', 'Q14534']","Terbinafine is an allylamine antifungal that inhibits squalene epoxidase (also known as squalene monooxygenase) to prevent the formation of ergosterol and cause an accumulation of squalene, weakening the cell wall of fungal cells.1,2,11Terbinafine distributes into tissues and has a long terminal elimination half life, so the duration of action is long.1Overdose with terbinafine is rare, even above the therapeutic dose, so the therapeutic index is wide.10,11Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.10",CN(C\C=C\C#CC(C)(C)C)CC1=CC=CC2=CC=CC=C12,"Terbinafine inhibits the enzyme squalene monooxygenase (also called squalene epoxidase), preventing the conversion of squalene to ,-oxydosqualene, a step in the synthesis of ergosterol.,,This inhibition leads to decreased ergosterol, which would normally be incorporated into the cell wall, and accumulation of squalene.,Generation of a large number of squalene containing vesicles in the cytoplasm may leach other lipids away from, and further weaken, the cell wall.TargetActionsOrganismASqualene monooxygenaseinhibitorYeastNSqualene monooxygenaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Allylamine Antifungal', 'Allylamines', 'Anti-Infective Agents', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Systemic Use', 'Antifungals for Topical Use', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Naphthalenes']" +DB00758,Clopidogrel,"Clopidogrelis an antiplatelet agent used to prevent blood clots in peripheral vascular disease, coronary artery disease, and cerebrovascular disease.",['Q9H244'],"Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke.3,9It has a long duration of action as it is taken once daily and a large therapeutic window as it is given in doses of 75-300mg daily.9",[H][C@@](N1CCC2=C(C1)C=CS2)(C(=O)OC)C1=CC=CC=C1Cl,"Clopidogrel is activated via a steps reaction to an active thiol-containing metabolite.This active form is a platelet inhibitor that irreversibly binds to PYADP receptors on platelets.This binding prevents ADP binding to PYreceptors, activation of the glycoprotein GPIIb/IIIa complex, and platelet aggregation.TargetActionsOrganismAPY purinoceptor antagonistHumans",[],"['Antiplatelet agents', 'Blood and Blood Forming Organs', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Platelet Aggregation', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein substrates', 'P2Y12 Platelet Inhibitor', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P2 Receptor Antagonists', 'Purinergic P2Y Receptor Antagonists', 'Pyridines', 'Sulfur Compounds', 'Thienopyridines', 'Thiophenes']" +DB01611,Hydroxychloroquine,Hydroxychloroquineis an antimalarial medication used to treat uncomplicated cases of malaria and for chemoprophylaxis in specific regions. Also a disease modifying anti-rheumatic drug (DMARD) indicated for treatment of rheumatoid arthritis and lupus erythematosus.,"['Q9NYK1', 'Q9NR96', 'Q9BYF1']","Hydroxychloroquine affects the function of lysosomes in humans as well as plasmodia.4Altering the pH of the lysosomes reduces low-affinity self-antigen presentation in autoimmune diseases and interferes with the ability of plasmodia to proteolyze hemoglobin for their energy requirements.4Hydroxychloroquine has a long duration of action as it may be taken on a weekly basis for some indications.13Hydroxychloroquine may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels.13Hydroxychloroquine is active against the erythrocytic forms of chloroquine-sensitive strains of P. falciparum, P. malariae, P. vivax, and P. ovale. Hydroxychloroquine is not active against the gametocytes and exoerythrocytic forms including the hypnozoite liver stage forms of P. vivax and P. ovale.15Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported.13",CCN(CCO)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1,"The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole.This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite.Hydroxychloroquine can also interfere with the action of parasitic heme polymerase, an enzyme that uses ferriprotoporphyrin IX (FP) released from hemoglobin as a substrate to form beta-hematin. By reducing the activity of heme polymerase without inhibiting the release of FP, hydroxychloroquine leads to the accumulation of FP in a toxic form.Hydroxychloroquine accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response.Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface.Self peptides bind to MHC complexes with low affinity and so they will be less likely to be presented to autoimmune T cells.Hydroxychloroquine also reduces the release of cytokines like interleukin- and tumor necrosis factor, possibly through inhibition of Toll-like receptors.,The raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-) from utilizing their activity for fusion and entry into the cell.Hydroxychloroquine inhibits terminal glycosylation of ACE, the receptor that SARS-CoV and SARS-CoV- target for cell entry.,ACE that is not in the glycosylated state may less efficiently interact with the SARS-CoV- spike protein, further inhibiting viral entry.TargetActionsOrganismAToll-like receptor antagonistHumansAToll-like receptor antagonistHumansADNAcross-linking/alkylationHumansUAngiotensin-converting enzyme modulatorHumans",[],"['Aminoquinolines', 'Anti-Infective Agents', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Antirheumatic Agents', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines']" +DB00727,Nitroglycerin,"Nitroglycerinis a nitrate vasodilator used to treat or prevent angina, heart failure, hypertension, and anal fissures.",['P16066'],"Nitroglycerin causes the relaxation of vascular smooth muscles, causing arteriolar and venous dilatation.17It increases blood flow to the myocardium and reduces cardiac preload and afterload, decreasing myocardial wall stress and ameliorating anginal symptoms.3,10,12Nitroglycerin also reduces coronary artery spasm, decreasing systemic vascular resistance as well as systolic and diastolic blood pressure.17Like other organic nitrates, repeated and prolonged administration of nitroglycerin can lead to the development of tolerance or desensitization of vascular smooth muscle to further nitroglycerin-induced vasorelaxation. This loss of efficacy may be associated with the inhibition of mitochondrial aldehyde dehydrogenase, which is an important enzyme involved in the bioactivation of nitroglycerin.1,2,3Nitroglycerin tolerance may be accompanied by pro-oxidant effects, endothelial dysfunction, and increased sensitivity to vasoconstrictors.3",[O-][N+](=O)OCC(CO[N+]([O-])=O)O[N+]([O-])=O,"Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase in smooth muscle cells to nitric oxide (NO), a potent vasodilator. NO activates the enzyme guanylate cyclase, which converts guanosine triphosphate (GTP) to cyclic guanosine ','-monophosphate (cGMP) in vascular smooth muscle and other tissues.,,cGMP is an endogenous vasodilator of vascular smooth muscle:it causes protein kinase-dependent phosphorylation and activates downstream cascades that promote relaxation and increased blood flow in veins, arteries and cardiac tissue.,Anin vitrostudy using mouse aorta suggests that nitric oxide, an active metabolite of nitroglycerin, targets the natriuretic peptide receptors.TargetActionsOrganismUAtrial natriuretic peptide receptor agonistHumans",[],"['Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Antianginal Agents', 'Antihypertensive Agents', 'Cardiac Therapy', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Explosive Agents', 'Hypotensive Agents', 'Methemoglobinemia Associated Agents', 'Nitrate Vasodilator', 'Nitrates and Nitrites', 'Nitro Compounds', 'Organic Nitrates', 'Vasodilating Agents', 'Vasodilation', 'Vasodilators Used in Cardiac Diseases', 'Vasoprotectives']" +DB00678,Losartan,"Losartanis an angiotensin receptor blocker used to treat hypertension and diabetic nephropathy, and is used to reduce the risk of stroke.",['P30556'],"Losartan is an angiotensin II receptor blocker used to treat hypertension, diabetic nephropathy, and to reduce the risk of stroke.1,3,4Losartan has a long duration of action as it is given once daily.3,4Patients taking losartan should be regularly monitored for hypotension, renal function, and potassium levels.3,4",CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1,"Losartan reversibly and competitively prevents angiotensin II binding to the ATreceptor in tissues like vascular smooth muscle and the adrenal gland.,Losartan and its active metabolite bind the ATreceptor with times more affinity than they bind to the ATreceptor.,The active metabolite of losartan is - times more potent by weight than unmetabolized losartan as an inhibitor of ATand is a non-competitive inhibitor.,Losartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation, lowering blood pressure.,Angiotensin II would otherwise bind to the ATreceptor and induce vasoconstriction, raising blood pressure.,TargetActionsOrganismAType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II receptor antagonists', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin II Type 1 Receptor Blockers', 'Angiotensin II Type 2 Receptor Blockers', 'Angiotensin Receptor Antagonists', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzene Derivatives', 'Biphenyl Compounds', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Hypotensive Agents', 'Imidazoles', 'OAT1/SLC22A6 inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Tetrazoles', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B17 substrates', 'UGT2B7 substrates']" +DB00546,Adinazolam,"Adinazolam (Deracyn®) is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative, and antidepressant properties. Adinazolam was first developed to enhance the antidepressant effects ofalprazolam. It has never been approved by the FDA for clinical use.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Adinazolam is a benzodiazepine derivative used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia. Adinazolam binds with high affinity to the GABA benzodiazepine receptor complex. Considerable evidence suggest that the central pharmacologic/therapeutic actions of alprazolam are mediated via interaction with this receptor complex.",CN(C)CC1=NN=C2CN=C(C3=CC=CC=C3)C3=C(C=CC(Cl)=C3)N12,"Adinazolam binds to peripheral-type benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Antidepressive Agents', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Psycholeptics', 'Psychotropic Drugs', 'Triazolobenzodiazepines']" +DB00458,Imipramine,Imipramineis a tricyclic antidepressant indicated for the treatment of depression and to reduce childhood enuresis.,"['P23975', 'P31645', 'P28223', 'P35367', 'P35348', 'P25100', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'Q9NZV8', 'Q9UK17', 'P28335', 'P35368', 'P34969', 'P21728', 'P21918', 'P14416', 'Q12809', 'Q01959', 'P08908', 'P50406', 'O95259', 'P19652']","Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. While it acts to block both, imipramine displays a much higher affinity for the serotonin reuptake transporter than for the norepinephrine reuptake transporter5. Imipramine produces effects similar to other monoamine targeting antidepressants, increasing serotonin- and norepinephrine-based neurotransmission.This modulation of neurotransmission produces a complex range of changes in brain structure and function along with an improvement in depressive symptoms. The changes include increases in hippocampal neurogenesis and reduced downregulation of this neurogenesis in response to stress6. These implicate brain derived neurotrophic factor signalling as a necessary contributor to antidepressant effect although the link to the direct increase in monoamine neurotransmission is unclear.Serotonin reuptake targeting agents may also produce a down-regulation in β-adrenergic receptors in the brain8.",CN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12,"Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin,. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signalling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansU-hydroxytryptamine receptor AantagonistHumansNHistamine H receptorantagonistHumansNAlpha-A adrenergic receptorantagonistHumansNAlpha-D adrenergic receptorantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNPotassium voltage-gated channel subfamily D member inhibitorHumansNPotassium voltage-gated channel subfamily D member inhibitorHumansU-hydroxytryptamine receptor CantagonistbinderHumansUAlpha-B adrenergic receptorantagonistHumansU-hydroxytryptamine receptor antagonistHumansUD() dopamine receptorbinderHumansUDopamine D receptorbinderHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUSodium-dependent dopamine transporterinhibitorHumansU-hydroxytryptamine receptor AactivatorHumansU-hydroxytryptamine receptor binderHumansUPotassium voltage-gated channel subfamily H member Not AvailableHumansUAlpha--acid glycoprotein Not AvailableHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dibenzazepines', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tertiary amine tricyclic antidepressants', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB00404,Alprazolam,Alprazolamis a triazolobenzodiazepine with intermediate onset commonly used to treat panic disorders and generalized anxiety in addition to anxiety associated with depression.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Alprazolam is a benzodiazepine that binds γ-aminobutyric acid (GABA) type-A receptors (GABAARs) to enhance their inhibitory effect on neurotransmission, specifically in the brain.18,19Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death; patients taking benzodiazepines and opioids concurrently may require lower doses of one or both medications, depending on their clinical situation. Patients with pre-existing impaired respiratory function are at increased risk of adverse effects including death during treatment with benzodiazepines. In addition, due to its CNS depressant effects, patients taking alprazolam should avoid operating heavy machinery or driving and should avoid other CNS depressants such as alcohol. As with other benzodiazepines, alprazolam carries a risk of abuse, misuse, and addiction, which is higher in predisposed individuals and may require strict monitoring. Cessation of therapy may result in acute or protracted withdrawal symptoms, which may be life-threatening; the patient dose should be gradually tapered whenever discontinuation or reduced dosage are necessary. Newborns born to mothers using alprazolam later in pregnancy may suffer from sedation and withdrawal symptoms. As CYP3A is required for the initial step in alprazolam metabolism, alprazolam is contraindicated in patients taking strong CYP3A inhibitors, such as ketoconazole and itraconazole; milder CYP3A inhibitors still necessitate alprazolam dosage adjustments. Lastly, benzodiazepines may have negative effects, such as panic disorders, increased suicide incidence, and episodes of mania/hypomania, in patients suffering from depression.4,7,18,19",CC1=NN=C2CN=C(C3=CC=CC=C3)C3=C(C=CC(Cl)=C3)N12,"Neurotransmission relies on excitatory and inhibitory signalling. γ-aminobutyric acid (GABA) type-A receptors (GABAARs) are members of the pentameric ligand-gated ion channel (PLGIC) superfamily located synaptically and perisynaptically to mediate phasic inhibition and extrasynaptically to mediate tonic inhibition. GABAARs comprise a variety of subunits from a homologous family whose members are named based on sequence identity as one of α-, β-, γ-, δ, ε, θ, π, and ρ-. Each subunit possesses an extracellular (ECD), transmembrane (TMD), and intracellular (ICD) domain; inter-subunit interfaces are the primary points of neurotransmitter and modulator binding, described by coordination of the principal (+) and complementary (-) sites in each subunit. Binding of GABA to GABAARs induces pore opening, rapid flow of chloride ions, and synaptic hyperpolarization, which in turn manifests as an inhibitory signal.,The most prevalent GABAARsin vivoare the αβγ receptors, which contain both GABA (β+/α-) and benzodiazepine (BZD, α+/γ-) binding sites in the intersubunit interfaces of the relevant subunits.,,In general, any receptors containing an αx/γzinterface, where x = -, and z = -, have potential high-affinity BZD binding sites, although small sequence differences between subunits may alter binding affinity to individual molecules. The α and α subunits, in which an otherwise conserved histidine is replaced by arginine, do not bind traditional BZD ligands such as diazepam and hence are considered ""diazepam-insensitive"".,,GABA binding results in a series of conformational changes in the ECDs of GABAAR β subunits, ""locking"" each to its neighbouring α- interface. The binding of alprazolam in the high-affinity BZD site stabilizes the α+/γ- interface and facilitates the conformational changes that lead to pore opening, hence functioning as a positive allosteric modulator.The exact manner in which GABAAR allosteric modulation mediates the therapeutic and unwanted effects of benzodiazepines remains unclear.,Earlier studies suggested that the primary factor was the α subunit composition, with α-containing receptors mediating the sedative effects, α/-containing receptors the anxiolytic effects, and α-containing receptors the memory effects of benzodiazepines.More recent studies suggest a more complex set of factors including subunit composition, physiological location, neuronal circuit, and nerve cell type.To further complicate matters, there may be up to five distinct BZD binding sites on GABAARs, with site corresponding to the classical high-affinity α+/γ- interface. The effects of binding at sites - are not fully understood and likely impart greater complexity to benzodiazepine pharmacological action.,TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Amines', 'Anti-Anxiety Agents', 'Benzazepines', 'Benzene Derivatives', 'Benzodiazepines and benzodiazepine derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Catechols', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Ethanolamines', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'Triazolobenzodiazepines']" +DB04817,Metamizole,Metamizoleis an antipyretic and analgesic drug used to relieve severe and persistent fever and pain.,['P23219'],"Metamizole is a strong analgesic and antipyretic with spasmolytic properties. It has weak anti-inflammatory or antithrombotic properties and does not follow the same mechanism of action as conventional non-steroidal anti-inflammatory drugs (NSAIDs).1Metamizole can lead to agranulocytosis, a life-threatening side effect where a patient’s neutrophil count falls below 500 cells per microliter.1It has been shown that metamizole-induced agranulocytosis is caused by the development of drug-dependent anti-neutrophil antibodies requiring covalent binding of neutrophils to metamizole and its metabolites.2",CN(CS(O)(=O)=O)C1=C(C)N(C)N(C1=O)C1=CC=CC=C1,"The mechanism of action of metamizole is not fully understood. Its active metabolites, -methyl-amino-antipyrine (MAA) and -amino-antipyrine (AA), inhibit prostaglandin E (PGE)-induced hyperalgesia.It has been suggested that the anti-hyperalgesic effect of MAA is mediated by guanosine ','-cyclic monophosphate (cGMP) activation and ATP-sensitive potassium channel opening, while the effects of AA are associated with the activation of cannabinoid receptor type (CB).Metamizole is classified in some sources as a weak non-steroidal anti-inflammatory drug (NSAID);however, evidence suggests that its analgesic effects do not depend on its anti-inflammatory properties.Although the inhibition of cyclooxygenase (COX) may play a role in the central nervous system effects of metamizole,reports suggest that metamizole inhibits COX- with a higher affinity compared to COX- or COX-.,TargetActionsOrganismUProstaglandin G/H synthase Not AvailableHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Aminopyrine', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Antipyretics', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Nephrotoxic agents', 'Nervous System', 'Peripheral Nervous System Agents', 'Pyrazoles', 'Pyrazolones', 'Sensory System Agents']" +DB01607,Ticarcillin,Ticarcillinis a beta lactam antibiotic used to treat a variety of infections in the body.,['C1KC03'],"Ticarcillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. Ticarcillin is, however, susceptible to degradation by ß-lactamases, and therefore, the spectrum of activity does not normally include organisms which produce these enzymes.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](C(O)=O)C1=CSC=C1)C(O)=O,"Ticarcillin's principal mechanism of action revolves around its capacity to prevent the cross-linking of peptidoglycan during bacterial cell wall synthesis. Consequently, when the offending bacteria attempt to undergo cell division, cell death occurs.TargetActionsOrganismAPenicillin binding protein ainhibitorStaphylococcus aureus",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB01140,Cefadroxil,"Cefadroxilis a cephalosporin antibiotic used in the treatment of various bacterial infections, such as urinary tract infections, skin and skin structure infections, and tonsillitis.","['Q75Y35', 'Q8DR59', 'Q7CRA4', 'P0A3M6']","Cefadroxil, a first-generation cephalosporin antibiotic, is used to treat urinary tract infections, skin and skin structure infections, pharyngitis, and tonsillitis.",[H][C@]12SCC(C)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O,"Like all beta-lactam antibiotics, cefadroxil binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefadroxil interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Drugs that are Mainly Renally Excreted', 'First-Generation Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Sulfur Compounds', 'Thiazines']" +DB00845,Clofazimine,Clofazimineis a riminophenazine antimycobacterial used to treat leprosy.,"['P37231', 'P22001']","Clofazimine exerts a slow bactericidal effect onMycobacterium leprae(Hansen's bacillus) due primarily to its action on the bacterial outer membrane, though there is some evidence that activity on the bacterial respiratory chain and ion transporters may play a role.2It also exerts anti-inflammatory properties due to the suppression of T-lymphocyte activity. Clofazimine has a relatively long duration of action owing to its long residence time in the body, but is still administered daily.Approximately 75-100% of patients receiving clofazimine will experience an orange-pink to brownish-black discoloration of the skin, conjunctivae, and bodily fluids.5Skin discoloration may take several months or years to reverse following the cessation of therapy. Clofazimine has also been implicated in abdominal obstruction, in some cases fatal, due to the deposition of drug and formation of crystals in the intestinal mucosa - complaints of abdominal pain and nausea/vomiting should be investigated promptly, and the doses of clofazimine should be lowered or discontinued if it is found to be the culprit.5Its use should be avoided in patients with hepatic dysfunction.5",CC(C)N=C1C=C2N(C3=CC=C(Cl)C=C3)C3=C(C=CC=C3)N=C2C=C1NC1=CC=C(Cl)C=C1,"Although the precise mechanism(s) of action of clofazimine have not been elucidated, its antimicrobial activity appears to be membrane-directed. It was previously thought that, due to its lipophilicity, clofazimine participated in the generation of intracellular reactive oxygen species (ROS) via redox cycling, specifically HOand superoxide, which then exerted an antimicrobial effect.A more recent and compelling theory involves clofazimine interacting with bacterial membrane phospholipids to generate antimicrobial lysophospholipids - bactericidal efficacy may, then, arise from the combined membrane-destabilizing effects of both clofazimine and lysophospholipids, which interfere with K+ uptake and, ultimately, ATP production.,The anti-inflammatory activity of clofazimine is the result of its inhibition of T-lymphocyte activation and proliferation.Several mechanisms have been proposed, including direct antagonism of T-cell Kv . potassium channels and indirect action by promoting the release of E-series prostaglandins and reactive oxygen species from bystander neutrophils and monocytes.TargetActionsOrganismUPeroxisome proliferator-activated receptor gammamodulatorHumansUPotassium voltage-gated channel subfamily A member antagonistHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Inflammatory Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Drugs for Treatment of Lepra', 'Heterocyclic Compounds, Fused-Ring', 'Leprostatic Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phenazines', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB08805,Metiamide,Metiamide is an H-2 receptor antagonist derived from burimamide. It was an intermediate product on the path to developing cimetidine.,['P25021'],"Metiamide is a histamine H2-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. Metiamide inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Metiamide include an increase in gastric bacterial flora such as nitrate-reducing organisms.",CNC(=S)NCCSCC1=C(C)NC=N1,"Metiamide binds to an H-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Acid Reducers', 'Amides', 'Anti-Ulcer Agents', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H2 Antagonists', 'Neurotransmitter Agents', 'Sulfur Compounds', 'Thiourea']" +DB00812,Phenylbutazone,Phenylbutazoneis an NSAID used to treat backache and ankylosing spondylitis.,"['P23219', 'P35354', 'Q16647']","Phenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation",CCCCC1C(=O)N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1,Phenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide (HO) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansAProstacyclin synthaseinhibitorHumans,[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Butylpyrazolidines', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Peripheral Nervous System Agents', 'Pyrazoles', 'Pyrazolones', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain']" +DB00848,Levamisole,Levamisoleis levamisole is a nicotinic receptor agonist used to treat helminth infections and some skin infections.,"['P32297', 'P10696', 'Q23022', 'Q9N587', 'Q27218', 'P48181']","Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.",C1CN2C[C@@H](N=C2S1)C1=CC=CC=C1,"The mechanism of action of levamisole as an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is unknown. The effects of levamisole on the immune system are complex. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. Levamisole can stimulate formation of antibodies to various antigens, enhance T-cell responses by stimulating T-cell activation and proliferation, potentiate monocyte and macrophage functions including phagocytosis and chemotaxis, and increase neutrophil mobility, adherence, and chemotaxis.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-agonistHumansUAlkaline phosphatase, germ cell typeinhibitorHumansUAcetylcholine receptor subunit alpha-type unc-activatorCaenorhabditis elegansUAcetylcholine receptor subunit alpha-type unc-activatorCaenorhabditis elegansUAcetylcholine receptor subunit beta-type lev-activatorCaenorhabditis elegansUAcetylcholine receptor subunit beta-type unc-activatorCaenorhabditis elegans",[],"['Adjuvants, Immunologic', 'Anthelmintics', 'Anti-Infective Agents', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antirheumatic Agents', 'Imidazoles', 'Imidazothiazole Derivatives', 'Immunologic Factors', 'Levamisole, analogs & derivatives', 'Sulfur Compounds', 'Thiazoles']" +DB00208,Ticlopidine,"Ticlopidineis a platelet aggregation inhibitor used in the prevention of conditions associated with thrombi, such as stroke and transient ischemic attacks (TIA).",['Q9H244'],"Ticlopidine is a prodrug that is metabolised to an as yet undetermined metabolite that acts as a platelet aggregation inhibitor. Inhibition of platelet aggregation causes a prolongation of bleeding time. In its prodrug form, ticlopidine has no significant in vitro activity at the concentrations attained in vivo.",ClC1=CC=CC=C1CN1CCC2=C(C1)C=CS2,"The active metabolite of ticlopidine prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of ticlopidine.TargetActionsOrganismAPY purinoceptor antagonistHumans",[],"['Antiplatelet agents', 'Blood and Blood Forming Organs', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Platelet Aggregation', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Fibrin Modulating Agents', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Neurotransmitter Agents', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P2 Receptor Antagonists', 'Purinergic P2Y Receptor Antagonists', 'Pyridines', 'Sulfur Compounds', 'Thienopyridines', 'Thiophenes']" +DB01331,Cefoxitin,"Cefoxitinis a semi-synthetic, broad-spectrum antibiotic for parenteral administration used for the treatment of serious bacterial infections, such as urinary tract infection, blood infection, bone and joint infection, and lower respiratory tract infection.","['P08506', 'P0AEB2', 'P0AFI5', 'P24228', 'P02918', 'P02919', 'P0AD68', 'Q75Y35', 'Q7CRA4', 'Q8DNB6', 'Q8DR59', 'P0A3M6']","Cefoxitin is a cephamycin antibiotic often grouped with the second-generation cephalosporins. It is active against a broad range of gram-negative bacteria including anaerobes. The methoxy group in the 7a position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria.",[H][C@]12SCC(COC(N)=O)=C(N1C(=O)[C@]2(NC(=O)CC1=CC=CS1)OC)C(O)=O,The bactericidal action of cefoxitin results from inhibition of cell wall synthesis.TargetActionsOrganismAD-alanyl-D-alanine carboxypeptidase DacCinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacAinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine endopeptidaseinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacBinhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R),['Antibiotic pre-surgical prophylaxis'],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Cephamycins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB00446,Chloramphenicol,Chloramphenicolis a broad spectrum antibiotic that is effective against a variety of susceptible and serious bacterial infections but is not frequently used because of its high risk of bone marrow toxicity.,"['P0ADY7', 'P24093', 'P08174']","Chloramphenicol is a broad-spectrum antibiotic that was derived from the bacterium Streptomyces venezuelae and is now produced synthetically. Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). Chloramphenicol is bacteriostatic but may be bactericidal in high concentrations or when used against highly susceptible organisms. Chloramphenicol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis.",OC[C@@H](NC(=O)C(Cl)Cl)[C@H](O)C1=CC=C(C=C1)[N+]([O-])=O,"Chloramphenicol is lipid-soluble, allowing it to diffuse through the bacterial cell membrane. It then reversibly binds to the L protein of the S subunit of bacterial ribosomes, where transfer of amino acids to growing peptide chains is prevented (perhaps by suppression of peptidyl transferase activity), thus inhibiting peptide bond formation and subsequent protein synthesis.TargetActionsOrganismUS ribosomal protein LinhibitorEscherichia coli (strain K)UDr hemagglutinin structural subunitantagonistEscherichia coliUComplement decay-accelerating factorotherHumans",['Skin disinfection'],"['Alcohols', 'Amphenicols', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives for Systemic Use', 'Antiinfectives for Treatment of Acne', 'Benzene Derivatives', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Glycols', 'Gynecological Antiinfectives and Antiseptics', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Nitro Compounds', 'Nitrobenzenes', 'OAT1/SLC22A6 inhibitors', 'Ophthalmological and Otological Preparations', 'Ophthalmologicals', 'Otologicals', 'Propylene Glycols', 'Protein Synthesis Inhibitors', 'Sensory Organs']" +DB00679,Thioridazine,Thioridazineis a phenothiazine antipsychotic used to treat schizophrenia and generalized anxiety disorder.,"['P14416', 'P21728', 'P35348', 'P35368', 'P28223', 'Q12809']",Thioridazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Thioridazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.,CSC1=CC2=C(SC3=CC=CC=C3N2CCC2CCCCN2C)C=C1,"Thioridazine blocks postsynaptic mesolimbic dopaminergic D and D receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Hypotensive Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Phenothiazines', 'Phenothiazines With Piperidine Structure', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB01056,Tocainide,Tocainideis an orally active class 1b antiarrhythmic agent that interferes with cardiac sodium channels and typically used to treat ventricular arrhythmias.,['Q14524'],"Tocainide is a primary amine analog of lidocaine with antiarrhythmic properties useful in the treatment of ventricular arrhythmias. Tocainide, like lidocaine, produces dose dependent decreases in sodium and potassium conductance, thereby decreasing the excitability of myocardial cells. In experimental animal models, the dose-related depression of sodium current is more pronounced in ischemic tissue than in normal tissue. Tocainide is a Class I antiarrhythmic compound with electrophysiologic properties in man similar to those of lidocaine, but dissimilar from quinidine, procainamide, and disopyramide.",CC(N)C(=O)NC1=C(C)C=CC=C1C,"Tocainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. Tocainide binds preferentially to the inactive state of the sodium channels.The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",[],"['Amides', 'Amines', 'Anilides', 'Aniline Compounds', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ib', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Membrane Transport Modulators', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB00613,Amodiaquine,Amodiaquineis an antimalarial drug.,['P50135'],"Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 40 years. Amodiaquine is at least as effective as chloroquine, and is effective against some chloroquine-resistant strains, although resistance to amodiaquine has been reported. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension. They depress respiration and cause diplopia, dizziness and nausea.",CCN(CC)CC1=C(O)C=CC(NC2=C3C=CC(Cl)=CC3=NC=C2)=C1,"The mechanism of plasmodicidal action of amodiaquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. The drug binds the free heme preventing the parasite from converting it to a form less toxic. This drug-heme complex is toxic and disrupts membrane function.TargetActionsOrganismAFe(II)-protoporphyrin IXbinderPlasmodium falciparumUHistamine N-methyltransferaseinhibitorHumans",[],"['Aminoquinolines', 'Anti-Infective Agents', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines']" +DB01045,Rifampicin,"Rifampicinis an antibiotic used to treat several types of mycobacterial infections including Mycobacterium avium complex, leprosy, and in combination with other antibacterials to treat latent or active tuberculosis.","['P0A8V2', 'O75469']","Rifampin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (includingPseudomonas aeruginosa) and specificallyMycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.",CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C2=C(O)C(\C=N\N4CCN(C)CC4)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C(O)=C2C(O)=C3C,"Rifampin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.TargetActionsOrganismADNA-directed RNA polymerase subunit betainhibitorEscherichia coli (strain K)UNuclear receptor subfamily group I member agonistHumans",['Antibacterial therapy'],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics, Antitubercular', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'BSEP/ABCB11 Inhibitors', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (moderate)', 'Cytochrome P-450 CYP1A2 Inducers (strong)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2A6 Inducers (moderate)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (moderate)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (moderate)', 'Cytochrome P-450 CYP2C19 Inducers (strong)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strong)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (moderate)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strong)', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (strong)', 'Cytochrome P-450 CYP3A7 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs for Treatment of Lepra', 'Drugs for Treatment of Tuberculosis', 'Enzyme Inhibitors', 'Hepatotoxic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Lactams, Macrocyclic', 'Leprostatic Agents', 'Nucleic Acid Synthesis Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'OATP1B3 substrates', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'Rifamycin Antibacterial', 'Rifamycin Antimycobacterial', 'Rifamycins', 'UGT1A1 Inducers', 'UGT1A9 Inducers', 'UGT1A9 Inhibitors']" +DB00908,Quinidine,"Quinidineis a medication used to restore normal sinus rhythm, treat atrial fibrillation and flutter, and treat ventricular arrhythmias.","['Q14524', 'O00180', 'Q9Y257', 'Q12809', 'P35348', 'P35368', 'P25100']","Quinidine is an antimalarial schizonticide, and a class Ia antiarrhythmic agent used to interrupt or prevent reentrant arrhythmias and arrhythmias due to increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia.6In most patients, quinidine can lead to an increase in the sinus rate. Quinidine also causes a marked prolongation of the QT interval in a dose-related manner,1,5acts peripherally as an α-adrenergic antagonist, and has anticholinergic and negative inotropic activity.6The QT interval prolongation caused by quinidine can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such astorsades de pointes. The risk oftorsadesis increased by bradycardia, hypokalemia, hypomagnesemia or high serum levels of quinidine. However, this type of rhythm disturbance may appear in the absence of any of them.5,6Patients treated with quinidine may also be at risk of a paradoxical increase in ventricular rate in atrial flutter/fibrillation, and patients with sick sinus syndrome treated with quinidine may develop marked sinus node depression and bradycardia.5,6",[H][C@@]12CCN(C[C@@H]1C=C)[C@]([H])(C2)[C@@H](O)C1=C2C=C(OC)C=CC2=NC=C1,"Quinidine has a complex electrophysiological profile that has not been fully elucidated. The antiarrhythmic actions of this drug are mediated through effects on sodium channels in Purkinje fibers. Quinidine blocks the rapid sodium channel (INa), decreasing the phase zero of rapid depolarization of the action potential.Quinidine also reduces repolarizing K+currents (IKr, IKs), the inward rectifier potassium current (IK), and the transient outward potassium current Ito, as well as the L-type calcium current ICaand the late INainward current.The reduction of these currents leads to the prolongation of the action potential duration. By shortening the plateau but prolonging late depolarization, quinidine facilitates the formation of early afterdepolarisation (EAD).Additionally, in patients with malaria, quinidine acts primarily as an intra-erythrocytic schizonticide, and is gametocidal toPlasmodium vivaxandP. malariae, but not toP. falciparum.,TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUPotassium channel subfamily K member inhibitorHumansUPotassium channel subfamily K member inhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that produce neuromuscular block (indirect)', 'Agents that reduce seizure threshold', 'Alkaloids', 'Anti-Infective Agents', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ia', 'Anticholinergic Agents', 'Antimalarials', 'Antiparasitic Agents', 'Antiprotozoals', 'Biological Products', 'Biopolymers', 'BSEP/ABCB11 Inhibitors', 'Carbohydrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cholinergic Agents', 'Cinchona Alkaloids', 'Complex Mixtures', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Macromolecular Substances', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Negative Inotrope', 'Neurotransmitter Agents', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Pharmaceutical Preparations', 'Photosensitizing Agents', 'Plant Extracts', 'Plant Preparations', 'Polymers', 'Polysaccharides', 'QTc Prolonging Agents', 'Quinolines', 'Quinuclidines', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB06209,Prasugrel,"Prasugrelis a P2Y12 platelet inhibitor used to reduce risk of thrombotic cardiovascular events in unstable angina or non-ST-elevation myocardial infarction (NSTEMI), and in patients with STEMI when managed with either primary or delayed PCI.",['Q9H244'],Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 receptors.,CC(=O)OC1=CC2=C(CCN(C2)C(C(=O)C2CC2)C2=CC=CC=C2F)S1,"Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the PY receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel.TargetActionsOrganismAPY purinoceptor antagonistHumans",[],"['Anticoagulants', 'Antiplatelet agents', 'Blood and Blood Forming Organs', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Decreased Platelet Aggregation', 'Drugs that are Mainly Renally Excreted', 'Hematologic Agents', 'P2Y12 Platelet Inhibitor', 'Piperazines', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Purinergic P2Y Receptor Antagonists', 'Sulfur Compounds', 'Thiophenes']" +DB04570,Latamoxef,Latamoxef is a broad- spectrum beta-lactam antibiotic similar in structure to the cephalosporins except for the substitution of an oxaazabicyclo moiety for the thiaazabicyclo moiety of certain cephalosporins. It has been proposed especially for the meningitides because it passes the blood-brain barrier and for anaerobic infections.,"['P42971', 'P02918', 'P02919', 'P24228']",Latamoxef works by inhibiting bacterial cell wall biosynthesis.,[H][C@]12OCC(CSC3=NN=NN3C)=C(N1C(=O)[C@]2(NC(=O)C(C(O)=O)C1=CC=C(O)C=C1)OC)C(O)=O,"Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain (the penicillin-binding protein) by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that amoxicllin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorBacillus subtilis (strain )UPenicillin-binding protein AinhibitorEscherichia coli (strain K)UPenicillin-binding protein BinhibitorEscherichia coli (strain K)UD-alanyl-D-alanine carboxypeptidase DacBinhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Sulfides', 'Sulfur Compounds', 'Third-Generation Cephalosporins']" +DB00772,Malathion,Malathionis a parasympathomimetic organophosphate used to treat head lice.,['P06276'],"Malathion is an organophosphate insecticide commonly used to control mosquitos and other flying insects. Pharmaceutically, malathion is used to eliminate head lice. The principal toxicological effect of malathion is cholinesterase inhibition, due primarily to malaoxon and to phosphorus thionate impurities.",CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC,"Malathion is a nonsystemic, wide-spectrum organophosphate insecticide. It inhibits acetylcholinesterase activity of most eukaryotes. Malathion is toxic to aquatic organisms, but has a relatively low toxicity for birds and mammals. The major metabolites of malathion are mono- and di-carboxylic acid derivatives, and malaoxon is a minor metabolite. However, it is malaoxon that is the strongest cholinesterase inhibitor. Cholinesterases catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation. Because of its essential function, chemicals that interfere with the action of cholinesterase are potent neurotoxins, causing muscle spasms and ultimately death.TargetActionsOrganismACholinesteraseinhibitorHumans",[],"['Agrochemicals', 'Antiparasitic Products, Insecticides and Repellents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 Substrates', 'Ectoparasiticides, Incl. Scabicides', 'Ectoparasiticides, Incl. Scabicides, Insecticides and Repellents', 'Enzyme Inhibitors', 'Insecticides', 'Neurotransmitter Agents', 'Organophosphates', 'Organophosphorus Compounds', 'Organothiophosphates', 'Organothiophosphorus Compounds', 'Pesticides', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfur Compounds', 'Toxic Actions']" +DB00431,Lindane,Lindaneis an ectoparasiticide and ovicide used in the treatment of Pediculosis humanis capitis (head lice) and Phthirus pubis (crab lice).,"['P18505', 'P23415', 'P23416', 'O75311', 'P48167', 'P28472', 'P24046', 'P06401', 'P03372', 'O75469']","Scabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei (lice). It is a very contagious condition with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, scalp (hair), wrists, axillary folds, abdomen, buttocks, inframammary folds and genitalia (males). It is characterized by intense night-time itching. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Scabies infestations and the corresponding symptoms can be eliminated by killing the scabies with topical insecticides or scabicides. Lindane is a scabicide that is essentially an organochloride insecticide.",Cl[C@H]1[C@H](Cl)[C@@H](Cl)[C@@H](Cl)[C@H](Cl)[C@H]1Cl,"Lindane is an organochloride insecticide that has similar neurotoxic protperties to DDT. It exerts its parasiticidal action by being directly absorbed through the parasite's exoskeleton (primarily lice, or scabies) and their ova. The gamma-aminobutyric acid (GABA()) receptor/chloride ionophore complex is the primary site of action for lindane, and other insecticides such as endosulfan, and fipronil. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system. This results in paralysis, convulsions, and death. Lindane has very low ovicidal activity.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit beta-antagonistHumansUGlycine receptor subunit alpha-antagonistHumansUGlycine receptor subunit alpha-antagonistHumansUGlycine receptor subunit alpha-antagonistHumansUGlycine receptor subunit betaantagonistHumansUGamma-aminobutyric acid receptor subunit beta-Not AvailableHumansUGamma-aminobutyric acid receptor subunit rho-Not AvailableHumansUProgesterone receptorNot AvailableHumansUEstrogen receptor alphaNot AvailableHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['Agents that reduce seizure threshold', 'Agrochemicals', 'Antiparasitic Products, Insecticides and Repellents', 'Chlorine Containing Products', 'Compounds used in a research, industrial, or household setting', 'Ectoparasiticides, Incl. Scabicides', 'Ectoparasiticides, Incl. Scabicides, Insecticides and Repellents', 'Hydrocarbons, Chlorinated', 'Hydrocarbons, Halogenated', 'Insecticides', 'Pesticides', 'Toxic Actions']" +DB01075,Diphenhydramine,"Diphenhydramineis a H1 receptor antihistamine used in the treatment of seasonal allergies, and various allergic reactions including sneezing, runny nose, itchy/watery eyes, itching of nose or throat, pruritus, urticaria, insect bites/stings, and allergic rashes.","['P35367', 'P08172']","Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties12. The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone12. Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere12. Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone12. Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain12.",CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1,"Diphenhydramine predominantly works via the antagonism of H (Histamine ) receptors,,,,. Such H receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons,,,,. When the H receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response,,,,.Ultimately, diphenhydramine functions as an inverse agonist at H receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms,,,,. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H CNS receptors, resulting in drowsiness, and suppressing the medullary cough center,,,,.Furthermore, H receptors are similar to muscarinic receptors,,,,. Consequently, diphenhydramine also acts as an antimuscarinic,,,,. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication,,,,.Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties.TargetActionsOrganismAHistamine H receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans","['Airway secretion clearance therapy', 'Expectorant']","['Agents producing tachycardia', 'Amines', 'Aminoalkyl Ethers', 'Anesthetics', 'Anesthetics, Local', 'Anti-Allergic Agents', 'Anticholinergic Agents', 'Antiemetics', 'Antihistamines for Systemic Use', 'Antihistamines for Topical Use', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Benzene Derivatives', 'Benzhydryl Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Ethanolamine Derivatives', 'Ethylamines', 'First Generation Antihistamines', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hypnotics and Sedatives', 'Muscarinic Antagonists', 'OCT2 Inhibitors', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sleep Aids, Pharmaceutical']" +DB01411,Pranlukast,Pranlukastis a leukotriene receptor antagonist for the treatment of allergic rhinitis and asthma symptoms.,"['Q9Y271', 'P01375', 'P05113', 'P12724', 'P19838', 'Q02817', 'Q00653', 'P19838']",Pranlukast is a cysteinyl leukotriene receptor-1 antagonist.,O=C(NC1=C2OC(=CC(=O)C2=CC=C1)C1=NNN=N1)C1=CC=C(OCCCCC2=CC=CC=C2)C=C1,"Pranlukast selectively antagonizes leukotriene D(LTD) at the cysteinyl leukotriene receptor, CysLT, in the human airway. Pranlukast inhibits the actions of LTDat the CysLTreceptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.TargetActionsOrganismACysteinyl leukotriene receptor antagonistHumansUTumor necrosis factorother/unknownHumansUInterleukin-antagonistHumansUEosinophil cationic proteinother/unknownHumansUNuclear factor NF-kappa-B p subunitother/unknownHumansUMucin-other/unknownHumansUNuclear factor NF-kappa-BinhibitorHumans",[],"['Agents to Treat Airway Disease', 'Anti-Asthmatic Agents', 'Benzopyrans', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Heterocyclic Compounds, Fused-Ring', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Leukotriene Antagonists', 'Pyrans', 'Respiratory System Agents']" +DB00474,Methohexital,Methohexitalis an anesthetic used to induce deep sedation.,['P14867'],"Methohexital, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.",CCC#CC(C)C1(CC=C)C(=O)NC(=O)N(C)C1=O,"Methohexital binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-antagonistHumans","['General Anesthesia', 'Induction of anesthesia therapy', 'Sedative therapy']","['Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Anticonvulsants', 'Barbiturates', 'Barbiturates, Plain', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Hypnotics and Sedatives', 'Nervous System', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones']" +DB01222,Budesonide,"Budesonideis a corticosteroid used to treat Crohn's disease, asthma, COPD, hay fever and allergies, and ulcerative colitis.","['P04150', 'P04083']","Budesonide is a glucocorticoid used to treat respiratory and digestive conditions by reducing inflammation.9,10,11,12,14,15,16It has a wide therapeutic index, as dosing varies highly from patient to patient.9,10,11,12,14,15,16Patients should be counselled regarding the risk of hypercorticism and adrenal axis suppression.9,10,11,12,14,15,16",[H][C@@]12C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUAnnexin AsubstrateHumans",['Maintenance therapy'],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents to Treat Airway Disease', 'Alimentary Tract and Metabolism', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'BSEP/ABCB11 Substrates', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids Acting Locally', 'Corticosteroids for Systemic Use', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (moderate)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Intestinal Antiinflammatory Agents', 'Nasal Preparations', 'OAT3/SLC22A8 Substrates', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Respiratory System Agents', 'Steroids']" +DB01189,Desflurane,Desfluraneis a general inhalation anesthetic for inpatient and outpatient surgery in adults.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P23415', 'P42261', 'Q09470', 'P03886', 'P98194', 'O75185', 'P20020', 'Q01814', 'Q16720', 'P23634', 'O14983', 'P16615', 'P30049']","Desflurane is a general inhalation anesthetic.22It has a short duration of action as it is rapidly cleared.22Patients should be counselled regarding the risks of malignant hyperthermia, perioperative hyperkalemia, respiratory adverse reactions in pediatric patients, QTc prolongation, hepatobiliary disorders, pediatric neurotoxicity, and postoperative agitation in children.22",FC(F)OC(F)C(F)(F)F,"The mechanism of inhalational anesthetics is still not fully understood.They can block excitatory ion channels and increase the activity of inhibitory ion channels.The most notable agonism is at the GABAAchannel.Desflurane is also an agonist of glycine receptors,antagonist of glutamate receptors,inducer of potassium voltage gated channels,and inhibits both NADH-ubiquinone oxioreductase chain and calcium transporting ATPases.An older school of thought is the unitary theory of general anesthetic action, suggesting that desflurane affects the lipid bilayer of cells.,Studies of other halogenated inhalational anesthetics have shown that the lipid bilayer spreads out more thinly as the anesthetic incorporates into the bilayer.However, the anesthetic does not bind to lipid heads or acyl chains of hydrocarbons in the bilayer.The effect of incorporating into the lipid bilayer is not well described.,By incorporating into the lipid bilayer, anesthetics may introduce disorder in the lipids, leading to some indirect effect on ion channels.However, this theory remains controversial.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGlycine receptor subunit alpha-agonistHumansAGlutamate receptor antagonistHumansAPotassium voltage-gated channel subfamily A member inducerHumansANADH-ubiquinone oxidoreductase chain inhibitorHumansACalcium transporting ATPasesinhibitorHumansUATP synthase subunit delta, mitochondrialother/unknownHumans","['Induction and Maintenance of General Anesthesia', 'Maintenance of anesthesia therapy']","['Agents that produce hypertension', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Inhalation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Substrates', 'Ethers', 'Ethyl Ethers', 'Hydrocarbons, Fluorinated', 'Hydrocarbons, Halogenated', 'Hypotensive Agents', 'Methyl Ethers', 'Nervous System', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB01400,Neostigmine,Neostigmineis a cholinesterase inhibitor used in the symptomatic treatment of myasthenia gravis by improving muscle tone.,['P22303'],"Neostigmine is a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. By inhibiting acetylcholinesterase, more acetylcholine is available in the synapse, therefore, more of it can bind to the fewer receptors present in myasthenia gravis and can better trigger muscular contraction.",CN(C)C(=O)OC1=CC(=CC=C1)[N+](C)(C)C,"Neostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. The drug inhibits acetylcholinesterase which is responsible for the degredation of acetylcholine. So, with acetylcholinesterase inhibited, more acetylcholine is present By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors which are involved in muscle contraction.. It does not cross the blood-brain barrier.TargetActionsOrganismAAcetylcholinesteraseinhibitorHumans",[],"['Amines', 'Antiglaucoma Preparations and Miotics', 'Autonomic Agents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Enzyme Inhibitors', 'Nervous System', 'Neurotransmitter Agents', 'Onium Compounds', 'Ophthalmologicals', 'Parasympathomemetic (Cholinergic) Agents', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Phenylammonium Compounds', 'Quaternary Ammonium Compounds', 'Sensory Organs']" +DB00572,Atropine,"Atropineis a muscarinic antagonist used to treat poisoning by muscarinic agents, including organophosphates and other drugs.","['P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P23415', 'P43681', 'P17787']","Atropine is an antimuscarinic agent that antagonizes the effects of acetylcholine.5,6,8In small doses, atropine slows heart rate, and tachycardia develops due to paralysis of vagal control. Compared toscopolamine, atropine has a more potent and prolonged effect on the heart, intestine and bronchial muscle, but a weaker effect on the iris, ciliary body and certain secretory glands. Atropine leads to increased respiratory rate and depth of respiration, possibly due to the drug-induced bronchiolar dilatation rather than its mild effect on vagal excitation.8At an adequate dose, atropine abolishes different types of reflex vagal cardiac slowing or asystole. Atropine can be used to prevent or abolish bradycardia or asystole induced by the injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus.8When vagal activity is an etiologic factor, atropine may also lessen the degree of partial heart block. In clinical doses, atropine counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure.8The use of topical atropine in the eye induces mydriasis by inhibiting the contraction of the circular pupillary sphincter muscle normally stimulated by acetylcholine. This results in the contraction of the countering radial pupillary dilator muscle and pupil dilation.7The use of atropine may precipitate acute glaucoma and convert partial organic pyloric stenosis into complete obstruction. Atropine may also lead to complete urinary retention in patients with prostatic hypertrophy and cause the thickening of bronchial secretions and formation of viscid plugs in patients with chronic lung disease.8",CN1[C@H]2CC[C@@H]1C[C@@H](C2)OC(=O)C(CO)C1=CC=CC=C1,"Atropine binds to and inhibits muscarinic acetylcholine receptors, competitively blocking the effects of acetylcholine and other choline esters.,,It acts as a reversible non-specific antagonist of muscarinic receptors, showing affinity for the M, M, M, M and M receptor subtypes.Atropine antagonizes the effects of acetylcholine on tissues innervated by postganglionic cholinergic nerves, such as smooth muscle, cardiac tissue, exocrine glands and the central nervous system. Also, it acts in less innervated smooth muscle that responds to endogenous acetylcholine.,The actions of atropine can be overcome by increasing the concentration of acetylcholine at receptor sites (for instance, the use of anticholinesterase agents that inhibit the hydrolysis of acetylcholine).TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansUGlycine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumans",[],"['Adjuvants, Anesthesia', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Alkaloids', 'Anti-Asthmatic Agents', 'Antiarrhythmic agents', 'Anticholinergic Agents', 'Antimuscarinics Antispasmodics', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Belladonna Alkaloids', 'Belladonna Alkaloids, Tertiary Amines', 'Belladonna and Derivatives, Plain', 'Bronchodilator Agents', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Cholinergic Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Mydriatics', 'Mydriatics and Cycloplegics', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'QTc Prolonging Agents', 'Respiratory System Agents', 'Sensory Organs', 'Solanaceous Alkaloids', 'Tropanes']" +DB00683,Midazolam,"Midazolamis a short-acting benzodiazepine with rapid onset that is commonly used in seizures, anesthesia and anxiety disorders.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928', 'P29274']","General effectsMidazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. Pharmacodynamic properties of midazolam and its metabolites, which are similar to those of other benzodiazepine drugs, include sedative, anxiolytic, amnestic, muscle relaxant, as well as hypnotic activities.20Benzodiazepines enhance the inhibitory action of the amino acid neurotransmitter gamma-aminobutyric acid (GABA). Receptors for GABA are targeted by many important drugs that affect GABA function and are commonly used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, and aggressive behavior.7Sedation and memoryThe onset of sedation after intramuscular administration in adults is 15 minutes, with maximal sedation occurring 30-60 minutes after injection.LabelIn one study of adults, when tested the following day, 73% of the patients who were administered midazolam intramuscularly had no recollection of memory cards shown 30 minutes following drug administration; 40% had no recollection of the memory cards shown 60 minutes after drug administration. Onset time of sedative effects in pediatric patients begins within 5 minutes and peaks at 15-30 minutes depending upon the dose administered. In the pediatric population, up to 85% had no memory of pictures shown after receiving intramuscular midazolam compared to 5% of the placebo control group.20Sedation in both adult and pediatric patients is reached within 3 to 5 minutes post intravenous (IV) injection. The time of onset is affected by the dose administered and the simultaneous administration of narcotic pre-medication. Seventy-one (71%) percent of the adult patients in clinical endoscopy studies had no memory of insertion of the endoscope; 82% of the patients had no memory of withdrawal of the endoscope.14Anesthesia inductionWhen midazolam is administered intravenously (IV) for anesthetic induction, induction of anesthesia occurs in about 1.5 minutes when narcotic pre-medication has been given and in 2 to 2.5 minutes without narcotic pre-medication/ other sedative pre-medication. Impairment in a memory test was observed in 90% of the patients.14",CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12,"The actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the central nervous system. Benzodiazepines increase the activity of GABA, thereby producing a sedating effect, relaxing skeletal muscles, and inducing sleep, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening.These receptors have been identified in different body tissues including the heart and skeletal muscle, although mainly appear to be present in the central nervous system.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumansUAdenosine receptor AapotentiatorHumans","['Anaesthesia', 'Anxiolytic therapy therapy', 'Sedation for mechanically-ventilated patients', 'Preoperative amnesia therapy', 'Preoperative sedation therapy']","['Adjuvants, Anesthesia', 'Anesthetics', 'Anti-Anxiety Agents', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'Triazolobenzodiazepines', 'UGT1A4 substrates', 'UGT2B7 substrates']" +DB00181,Baclofen,Baclofenis a GABA-ergic agonist used to manage severe spasticity of cerebral or spinal origin in adult and pediatric patients.,"['O75899', 'P61073', 'Q9UBS5']","Baclofen is an antispasmodic agent that induces muscle relaxation. It reduces the release of excitatory neurotransmitters in the pre-synaptic neurons and stimulates inhibitory neuronal signals in the post-synaptic neurons.6Oral formulations of baclofen are the most commonly used form of the drug. In one cross-section study, intrathecal baclofen was more effective than oral baclofen in relieving spasticity directly at the level of the spinal cord.8Baclofen has CNS depression properties and can cause sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.13Baclofen also mediates some antinociceptive effects and stimulates gastric acid secretion.15Baclofen exhibits anti-inflammatory and neuroprotective activities: it inhibits the release of pro-inflammatory cytokines from microglia and astrocytes, and decreases oxidative stress in rats.5",NCC(CC(O)=O)C1=CC=C(Cl)C=C1,"The exact mechanism of action of baclofen is unclear. Baclofen is an agonist at the beta subunit of gamma-aminobutyric acid (GABA) receptors expressed on pre- and post-synaptic neurons.Upon binding to GABABreceptors, baclofen causes an influx of potassium into the neuron, leading to hyperpolarization of the neuronal membrane and decreased calcium influx at presynaptic nerve terminals. This results in a decreased rate of action potential threshold being reached by presynaptic neurons and reduced action potential of postsynaptic motor neurons that innervate the muscle spindles. Baclofen thereby inhibits the transmission of both mono- and polysynaptic reflexes at the spinal cord, relaxing spasticity.Baclofen may act on some voltage-gated calcium channels; however, the clinical significance of this is unclear.TargetActionsOrganismAGamma-aminobutyric acid type B receptor subunit agonistHumansUC-X-C chemokine receptor type allosteric modulatorHumansUGamma-aminobutyric acid type B receptor subunit agonistHumans",[],"['Agents Causing Muscle Toxicity', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Aminobutyrates', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Agonists', 'GABA-B Receptor Agonists', 'Gaba-derivative Skeletal Muscle Relaxants', 'gamma-Aminobutyric Acid-ergic Agonist', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neurotransmitter Agents']" +DB00422,Methylphenidate,Methylphenidateis a stimulant used in the management of Attention Deficit Hyperactivity Disorder (ADHD).,"['Q01959', 'P08908', 'P23975']","Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. Radioligand binding studies demonstrate that binding of methylphenidate in the brain is localized to dopamine-rich areas, in particular in the prefrontal cortex which has been demonstrated to play a prominent role in ADHD pathophysiology.8In a number of animal models, methylphenidate enhances locomotor activity and induces stereotypic behaviours.",COC(=O)C(C1CCCCN1)C1=CC=CC=C1,"While its exact mechanism is unclear, methylphenidate (MPH) has been shown to act as a norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extraneuronal space and prolonging their action.There is a dose-related effect of psychostimulants on receptor stimulation, where higher doses are shown to increase norepinephrine (NE) and dopamine (DA) efflux throughout the brain which can result in impaired cognition and locomotor-activating effects. In contrast, low doses are found to selectively activate NE and DE neurotransmission within the prefrontal cortex which is an area of the brain thought to play a prominent role in ADHD pathophysiology, thereby improving clinical efficacy and preventing side effects.The lower doses used to treat ADHD are not associated with the locomotor-activating effects associated with higher doses and instead reduce movement, impulsivity, and increase cognitive function including sustained attention and working memory.,Methylphenidate's beneficial effects in sustaining attention have also been shown to be mediated by alpha- adrenergic receptor activity.Clinical findings have shown that children with ADHD have an abnormality in the dopamine transporter gene (DAT), the D receptor gene (DRD-), and/or the D receptor gene that may be at least partly overcome by the dopaminergic effects of methylphenidate, suggesting a possible mode of action.TargetActionsOrganismASodium-dependent dopamine transporterinhibitorHumansU-hydroxytryptamine receptor ANot AvailableHumansUSodium-dependent noradrenaline transporterinhibitorHumans",[],"['Acids, Carbocyclic', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Centrally Acting Sympathomimetics', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Membrane Transport Modulators', 'Methylphenidate and isomer', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Phenylacetates', 'Piperidines', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Respiratory and CNS Stimulants']" +DB00808,Indapamide,Indapamideis a thiazide diuretic used to treat hypertension as well as edema due to congestive heart failure.,['P55017'],"Classified as a sulfonamide diuretic, indapamide is an effective antihypertensive agent and by extension, has shown efficacy in the prevention of target organ damage.2,3Administration of indapamide produces water and electrolyte loss, with higher doses associated with increased diuresis.2,10Severe and clinically significant electrolyte disturbances may occur with indapamide use - for example, hypokalemia resulting from renal potassium loss may lead to QTc prolongation.2,9Further electrolyte imbalances may occur due to renal excretion of sodium, chloride, and magnesium.2,9,10Other indapamide induced changes include increases in plasma renin and aldosterone, and reduced calcium excretion in the urine.2,11,15In many studies investigating the effects of indapamide in both non-diabetic and diabetic hypertensive patients, glucose tolerance was not significantly altered.2However, additional studies are necessary to assess the long term metabolic impacts of indapamide, since thiazide related impaired glucose tolerance can take several years to develop in non-diabetic patients.2",CC1CC2=CC=CC=C2N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O,"Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule where it inhibits the Na+/Cl- cotransporter, leading to reduced sodium reabsorption.,As a result, sodium and water are retained in the lumen of the nephron for urinary excretion.The effects that follow include reduced plasma volume, reduced venous return, lower cardiac output, and ultimately decreased blood pressure.Interestingly, it is likely that thiazide-like diuretics such as indapamide have additional blood pressure lowering mechanisms that are unrelated to diuresis.This is exemplified by the observation that the antihypertensive effects of thiazides are sustained - weeks after initiation of therapy, despite recovering plasma and extracellular fluid volumes.Some studies have suggested that indapamide may decrease responsiveness to pressor agents while others have suggested it can decrease peripheral resistance.Although it is clear that diuresis contributes to the antihypertensive effects of indapamide, further studies are needed to investigate the medication’s ability to decrease peripheral vascular resistance and relax vascular smooth muscle.TargetActionsOrganismASolute carrier family member inhibitorHumans",[],"['Amides', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis', 'Indoles', 'Lipid Modifying Agents', 'Low-Ceiling Diuretics, Excl. Thiazides', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Non Potassium Sparing Diuretics', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazide-like Diuretic']" +DB00622,Nicardipine,Nicardipineis a calcium channel blocker used for the short-term treatment of hypertension and chronic stable angina.,"['Q13936', 'Q08289', 'P54289', 'Q01668', 'P54750', 'Q01064', 'P35348', 'P35368', 'P25100', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P0DP23', 'Q06432', 'Q9Y698', 'O60359', 'Q9UBN1', 'Q9UF02', 'Q9BXT2', 'P62955', 'Q8WXS5', 'P54289', 'Q9NY47', 'Q8IZS8', 'Q7Z3S7', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'Q00975', 'O00555', 'Q15878', 'O43497', 'O95180', 'Q9P0X4', 'O43497', 'O95180', 'Q9P0X4']","Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.",COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OCCN(C)CC1=CC=CC=C1,"By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nicardipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansUCalcium/calmodulin-dependent ','-cyclic nucleotide phosphodiesterase AinhibitorHumansUCalcium/calmodulin-dependent ','-cyclic nucleotide phosphodiesterase BinhibitorHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUCalmodulinother/unknownHumansUVoltage-dependent calcium channelinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents causing hyperkalemia', 'Agents producing tachycardia', 'Antiarrhythmic agents', 'Anticholinergic Agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Substrates', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00136,Calcitriol,Calcitriolis an active metabolite of vitamin D that is used to treat hyperparathyroidism and is also used in dialysis patients to combat hypocalcemia.,"['P11473', 'P31260']","Calcitriol is a biologically active calcitrophic hormone with anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Its main sites of action are the intestine, bone, kidney and parathyroid hormoneLabel. Calcitriol is a ligand for the vitamin D nuclear receptor, which is expressed in, but not limited to, gastrointestinal (GI) tissues, bones, and kidneys1. As an active form of vitamin D3, calcitriol elevates the plasma levels of calcium by stimulating intestinal calcium uptake, increasing reabsorption of calcium by the kidneys, and possibly increasing the release of calcium from skeletal stores. The duration of pharmacologic activity of a single dose of exogenous calcitriol is expected to be about 3 to 5 daysLabel.In addition to its important role in calcium metabolism, other pharmacological effects of calcitriol have been studied in various conditions including cancer models. Various studies demonstrated expression of vitamin D receptors in cancer cell lines, including mouse myeloid leukemia cells1. Calcitriol has been found to induce differentiation and/or inhibit cell proliferationin vitroandin vivoin many cell types, such as malignant cell lines carcinomas of the breast, prostate, colon, skin, and brain, myeloid leukemia cells, and others2. In early human prostate cancer trials, administration of 1.5 µg/d calcitriol in male participants resulted in a reduction in the rate of PSA rise in most participants, however it was coincided with dose-limiting hypercalcemia in most participants1. Hypercalcemia and hypercalcuria were evident in numerous initial trials, and this may be due to these trials not testing the drug at concentrations that are active in preclinical systems2. Findings from preclinical data show an additive or synergistic antineoplastic action of calcitriol when combined with agents including dexamethasone, retinoids, and radiation, as well as several cytotoxic chemotherapy drugs such as platinum compounds2.Vitamin D deficiency has long been suspected to increase the susceptibility to tuberculosis. The active form of calcitriol, 1,25-(OH)2-D3, has been found to enhance the ability of mononuclear phagocytes to suppress the intracellular growth ofMycobacterium tuberculosis. 1,25-(OH)2-D3 has demonstrated beneficial effects in animal models of such autoimmune diseases as rheumatoid arthritis. Vitamin D appears to demonstrate both immune-enhancing and immunosuppressive effects.",C[C@H](CCCC(C)(C)O)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C,"The mechanism of action of calcitriol in the treatment of psoriasis is accounted for by their antiproliferative activity for keratinocytes and their stimulation of epidermal cell differentiation. The anticarcinogenic activity of the active form of Calcitriol appears to be correlated with cellular vitamin D receptor (VDR) levels. Vitamin D receptors belong to the superfamily of steroid-hormone zinc-finger receptors. VDRs selectively bind ,-(OH)-D and retinoic acid X receptor (RXR) to form a heterodimeric complex that interacts with specific DNA sequences known as vitamin D-responsive elements. VDRs are ligand-activated transcription factors. The receptors activate or repress the transcription of target genes upon binding their respective ligands. It is thought that the anticarcinogenic effect of Calcitriol is mediated via VDRs in cancer cells. The immunomodulatory activity of calcitriol is thought to be mediated by vitamin D receptors (VDRs) which are expressed constitutively in monocytes but induced upon activation of T and B lymphocytes. ,-(OH)-D has also been found to enhance the activity of some vitamin D-receptor positive immune cells and to enhance the sensitivity of certain target cells to various cytokines secreted by immune cells.A study suggests that calcitriol plays an immunoregulatry role by suppressing the aryl hydrocarbon receptor (AhR) expression in human Th, a pro-inflammatory CD T cell subset. This suppression subsequently leads to repressed expression of BATF, a transcription factor essential for Th. Calcitriol has also been found to induce monocyte differentiation and to inhibit lymphocyte proliferation and production of cytokines, including interleukin IL- and IL-, as well as to suppress immunoglobulin secretion by B lymphocytes.TargetActionsOrganismAVitamin D receptoragonistHumansUHomeobox protein Hox-ANot AvailableHumans",[],"['Alimentary Tract and Metabolism', 'Antipsoriatics', 'Antipsoriatics for Topical Use', 'Bone Density Conservation Agents', 'Calcium-Regulating Hormones and Agents', 'Cholestanes', 'Cholestenes', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Diet, Food, and Nutrition', 'Food', 'Fused-Ring Compounds', 'Growth Substances', 'Lipids', 'Membrane Lipids', 'Membrane Transport Modulators', 'Micronutrients', 'Misc. Skin and Mucous Membrane Agents', 'Physiological Phenomena', 'Secosteroids', 'Steroids', 'Sterols', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB01599,Probucol,"A drug used to lower LDL and HDL cholesterol yet has little effect on serum-triglyceride or VLDL cholesterol. (From Martindale, The Extra Pharmacopoeia, 30th ed, p993).","['O95477', 'P23141']","Probucol lowers cholesterol levels by increasing LDL (low-density lipoprotein) breakdown. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption. Probucol is a powerful antioxidant drug normally used to prevent vascular disease caused by the free radicals in the body.",CC(C)(SC1=CC(=C(O)C(=C1)C(C)(C)C)C(C)(C)C)SC1=CC(=C(O)C(=C1)C(C)(C)C)C(C)(C)C,"Probucol lowers serum cholesterol by increasing the fractional rate of low-density lipoprotein (LDL) catabolism in the final metabolic pathway for cholesterol elimination from the body. This drug may also act to inhibit the initial stages of cholesterol synthesis and act to inhibit the absorption of cholesterol from the diet. Recent information suggests that probucol may inhibit the oxidation and tissue deposition of LDL cholesterol, thereby inhibiting atherogenesis. It appears to inhibits ABCA-mediated cellular lipid efflux.TargetActionsOrganismAATP-binding cassette sub-family A member inhibitorHumansULiver carboxylesterase Not AvailableHumans",[],"['Anticholesteremic Agents', 'Antioxidants', 'Benzene Derivatives', 'Biological Factors', 'Compounds used in a research, industrial, or household setting', 'Hypolipidemic Agents', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Moderate Risk QTc-Prolonging Agents', 'Phenols', 'Protective Agents', 'QTc Prolonging Agents']" +DB00177,Valsartan,Valsartanis an angiotensin-receptor blocker used to manage hypertension alone or in combination with other antihypertensive agents and to manage heart failure in patients who are intolerant to ACE inhibitors.,['P30556'],"Valsartan inhibits the pressor effects of angiotensin II with oral doses of 80 mg inhibiting the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan.In multiple-dose studies in hypertensive patients, valsartan had no notable effects on total cholesterol, fasting triglycerides, fasting serum glucose, or uric acid.18HypotensionExcessive hypotension was rarely seen (0.1%) in patients with uncomplicated hypertension treated with valsartan alone. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of valsartan, or the treatment should start under close medical supervision.Caution should be observed when initiating therapy in patients with heart failure. Patients with heart failure given valsartan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients.If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.18Impaired Renal FunctionChanges in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on valsartan.18HyperkalemiaSome patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of valsartan may be required.18",CCCCC(=O)N(CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1)[C@@H](C(C)C)C(O)=O,"Valsartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which selectively bind to angiotensin receptor (AT) and prevent angiotensin II from binding and exerting its hypertensive effects. These include vasoconstriction, stimulation and synthesis of aldosterone and ADH, cardiac stimulation, and renal reabsorption of sodium among others. Overall, valsartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium.Valsartan also affects the renin-angiotensin aldosterone system (RAAS), which plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via AT receptor blockade inhibits negative regulatory feedback within RAAS which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and prevent ventricular hypertrophy.The angiotensin-converting enzyme inhibitor (ACEI) class of medications (which includes drugs such asramipril,lisinopril, andperindopril) inhibits the conversion of angiotensin I to angiotensin II by inhibiting the ACE enzyme but does not prevent the formation of all angiotensin II. ARB activity is unique in that it blocks all angiotensin II activity, regardless of where or how it was synthesized.Valsartan is commonly used for the management of hypertension, heart failure, and type diabetes-associated nephropathy, particularly in patients who are unable to tolerate ACE inhibitors. ARBs such as valsartan have been shown in a number of large-scale clinical outcomes trials to improve cardiovascular outcomes including reducing risk of myocardial infarction, stroke, the progression of heart failure, and hospitalization.,,,,,,,Valsartan also slows the progression of diabetic nephropathy due to its renoprotective effects.,,Improvements in chronic kidney disease with valsartan include both clinically and statistically significant decreases in urinary albumin and protein excretion in patients diagnosed with type diabetes and in nondiabetic patients diagnosed with chronic kidney disease.,Valsartan also binds to the AT receptor, however AT is not known to be associated with cardiovascular homeostasis like AT. Valsartan has about ,-fold higher affinity for the AT receptor than for the AT receptor. The increased plasma levels of angiotensin II following AT receptor blockade with valsartan may stimulate the unblocked AT receptor.TargetActionsOrganismAType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II Antagonists and Calcium Channel Blockers', 'Angiotensin II Antagonists and Diuretics', 'Angiotensin II receptor antagonists', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin II Type 1 Receptor Blockers', 'Angiotensin II Type 2 Receptor Blockers', 'Angiotensin Receptor Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates']" +DB09220,Nicorandil,Nicorandilis a vasodilatory drug that functions through potassium channels and intracellular cGMP concentrations commonly used to treat angina.,['O60706'],"Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator11. It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however the effect of the drug on coronary arteries does not involve the coronary steal phenomenon12. Activation of potassium channels lead to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through reduction of end-diastolix pressure and decreased extravascular component of vascular resistance12. Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris8.",[O-][N+](=O)OCCNC(=O)C1=CC=CN=C1,"Nicorandil mediates its therapeutic efficacy via two main mechanisms. Nicorandil is an activator and opener of ATP-sensitive (ATP-dependent) potassium channels (KATP channels) that are composed of Kir.x-type subunits and sulfonylurea receptor (SUR) subunits. Nicorandil binding sites are located in the sulfonylurea receptor (SUR) in the ATP-sensitive potassium channel, which are regulatory subunits of the channel that exhibit an ATPase activitiy. There are types of SUR subunits (A/B) that have identical nucleotide binding domains (NBD), where SURA is more predominantly expressed in skeletal and cardiac myocytes and SURB in smooth muscle cells. Nicorandil more potently activates SURB/Kir. than SURA/Kir. channels to cause hyperpolarization. ATP-NBD interaction influences the channel signalling by nicorandil, and the response of the channel to nicorandil is also facilitated and heightened by the interaction of ATP or ADP with NBD. Potentiated activity of ATP-sensitive channels have cardioprotective role by limiting the duration of action potentials and preventing intraceullar calcium overload. This attenuates cellular injury by preserving cellular energetics and ultimately cell survival. KATP channel-dependent membrane hyperpolarization can also lead to vasodilation via reduction in Ca+ influx through the voltage-gated Ca+ channels and regulation of intracellular Ca+ mobilization in smooth muscle cells. +Nicorandil contain a nitrate moiety in its structure, making it a good dilator of vascular smooth muscle like other nitroglycerin esters. Direct relaxation of venous vascular system arises from NO-donor mediated stimulation of guanylyl cyclase and increased levels of intracellular cyclic GMP (cGMP). Elevated levels of cGMP contributes to the total relaxing effect of nicorandil at higher concentrations of the drug.TargetActionsOrganismAATP-binding cassette sub-family C member activatorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Cardiac Therapy', 'Cardiovascular Agents', 'Drugs that are Mainly Renally Excreted', 'Micronutrients', 'Nicotinic Acids', 'Nitrates', 'Potassium Channel Opener', 'Pyridines', 'Vasodilating Agents', 'Vasodilators Used in Cardiac Diseases']" +DB00877,Sirolimus,"Sirolimusis an mTOR inhibitor immunosuppressant used to prevent organ transplant rejections, treat lymphangioleiomyomatosis, and treat adults with perivascular epithelioid cell tumors.",['P42345'],"Sirolimus is an immunosuppressant drug with antifungal and antitumour effects.2In animal models, sirolimus prolonged allograft survival following various organ transplants and reversed an acute rejection of heart and kidney allografts in rats. Upon oral administration of 2 mg/day and 5 mg/day, sirolimus significantly reduced the incidence of organ rejection in low- to moderate-immunologic risk renal transplant patients at six months following transplantation compared with either azathioprine or placebo. In some studies, the immunosuppressive effect of sirolimus lasted up to six months after discontinuation of therapy: this tolerization effect is alloantigen-specific.8Sirolimus potently inhibits antigen-induced proliferation of T cells, B cells, and antibody production.3In rodent models of autoimmune disease, sirolimus suppressed immune-mediated events associated with systemic lupus erythematosus, collagen-induced arthritis, autoimmune type I diabetes, autoimmune myocarditis, experimental allergic encephalomyelitis, graft-versus-host disease, and autoimmune uveoretinitis.8",[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](O)[C@@H](C1)OC,"Sirolimus works by inhibiting T-lymphocyte activation and proliferation stimulated by antigens and cytokines such as interleukin (IL)-, IL-, and IL-. In target cells, sirolimus binds to the cytoplasmic receptor FK-binding protein- (FKBP), an immunophilin, to form an immunosuppressive complex. FKBP-sirolimus complex binds to and inhibits the activation of the mammalian target of rapamycin (mTOR),,which is a serine/threonine-specific protein kinase that regulates cell growth, proliferation, survival, mobility, and angiogenesis.,mTOR regulates the downstream signalling pathways involved in cell survival, such as the phosphatidylinositol- kinase (PIK)/Akt signalling pathway.Inhibition of mTOR leads to the suppression of cytokine-driven T-cell proliferation, thus the progression from the G to the S phase of the cell cycle is inhibited. Sirolimus also inhibits antibody production.In vitro, sirolimus and other mTOR inhibitors inhibit the production of certain growth factors that may affect angiogenesis, fibroblast proliferation, and vascular permeability.Lymphangioleiomyomatosis is a disorder that primarily affects the lungs. It is characterized by lung tissue infiltration, unregulated alveolar smooth muscle proliferation, and cystic destruction of parenchyma. Although infrequent, it occurs as a symptomatic pulmonary complication in tuberous sclerosis complex (TSC), which is an inherited disorder caused by mutations in TSC genes.Loss of functional TSC gene leads to the aberrant activation of the mTOR signalling pathway, resulting in cellular proliferation and release of lymphangiogenic growth factors. Sirolimus inhibits the activated mTOR pathway and proliferation of alveolar smooth muscle cell proliferation.TargetActionsOrganismASerine/threonine-protein kinase mTORinhibitorHumans",[],"['Agents causing angioedema', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics, Antineoplastic', 'Antifungal Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Decreased Immunologic Activity', 'Hyperglycemia-Associated Agents', 'Immunologic Factors', 'Immunosuppressive Agents', 'Immunotherapy', 'Kinase Inhibitor', 'Lactones', 'Macrolides', 'Mammalian target of rapamycin (mTOR) kinase inhibitors', 'mTOR Inhibitor Immunosuppressant', 'mTOR Inhibitors', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'Ophthalmologicals', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Polyketides', 'Protein Kinase Inhibitors', 'Selective Immunosuppressants', 'Sensory Organs', 'Sirolimus and Prodrugs']" +DB05990,Obeticholic acid,Obeticholic acidis a bile acid analog and farnesoid X receptor agonist used to treat primary biliary cholangitis in adult patients with inadequate clinical response or intolerance to UDCA.,['Q96RI1'],"The activation of the FXR by obeticholic acid acts to reduce the synthesis of bile acids, inflammation, and the resulting hepatic fibrosis. This may increase the survival of patients with PBC, but to date, an association between obeticholic acid and survival in PBC has not been established.3,9",[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)[C@H](CC)[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O,"Primary biliary cirrhosis is an autoimmune process by which the bile ducts and liver are damaged progressively, leading to fibrosis and cirrhosis. Bile acids increase the risk of damage and fibrosis to the damaged bile ducts.,Obeticholic acid is a potent agonist of the farnesoid X receptor, which serves to regulate the hepatic metabolism of bile and cholesterol. This drug acts by binding to the farnesoid X receptor (FXR), found in the nucleus of liver and intestinal cells, which in turn increases liver bile flow, suppressing its production and decreasing hepatocyte exposure to excess levels of bile with cholestasis. Cholestasis is a process that normally causes inflammation and cirrhosis of the liver.,TargetActionsOrganismABile acid receptoragonistHumans",[],"['Alimentary Tract and Metabolism', 'Bile Acid Preparations', 'Bile acids and derivatives', 'Bile Acids and Salts', 'Bile and Liver Therapy', 'Bile Therapy', 'BSEP/ABCB11 inducers', 'BSEP/ABCB11 Inhibitors', 'Cholanes', 'Cholic Acids', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Farnesoid X Receptor Agonist', 'Farnesoid X Receptor Agonists', 'Fused-Ring Compounds', 'Miscellaneous GI Drugs']" +DB01132,Pioglitazone,Pioglitazoneis a thiazolidinedione used adjunctively with diet and exercise to normalize glycemic levels in adults with type 2 diabetes mellitus.,"['P37231', 'P27338']","Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis.1In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values.1Significant fluid retention leading to the development/exacerbation of congestive heart failure has been reported with pioglitazone - avoid its use in patients in heart failure or at risk of developing heart failure.4There is some evidence that pioglitazone may be associated with an increased risk of developing bladder cancer. Pioglitazone should not be used in patients with active bladder cancer and should be used with caution in patients with a history of bladder cancer.4",CCC1=CN=C(CCOC2=CC=C(CC3SC(=O)NC3=O)C=C2)C=C1,"Pioglitazone is a selective agonist at peroxisome proliferator-activated receptor-gamma (PPARγ) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver.,Activation of PPARγ increases the transcription of insulin-responsive genes involved in the control of glucose and lipid production, transport, and utilization.Through this mechanism, pioglitazone both enhances tissue sensitivity to insulin and reduces the hepatic production of glucose (i.e. gluconeogenesis) - insulin resistance associated with type diabetes mellitus is therefore improved without an increase in insulin secretion by pancreatic beta cells.,TargetActionsOrganismAPeroxisome proliferator-activated receptor gammaagonistHumansUAmine oxidase [flavin-containing] BinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Hypoglycemia-Associated Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Oral Hypoglycemics', 'Peroxisome Proliferator Receptor gamma Agonist', 'Peroxisome Proliferator-activated Receptor Activity', 'Sulfur Compounds', 'Thiazoles', 'Thiazolidinediones']" +DB00542,Benazepril,Benazeprilis an ACE inhibitor prodrug used to treat hypertension.,['P12821'],"Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by esterases to its active Benazeprilat1, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients5,3,2. Benazepril and Benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals5,1. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin IILabel. Angiotensin II also stimulates aldosterone secretion by the adrenal cortexLabel.",[H][C@@]1(CCC2=CC=CC=C2N(CC(O)=O)C1=O)N[C@@H](CCC1=CC=CC=C1)C(=O)OCC,"Benazeprilat, the active metabolite of Benazepril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin IILabel. Inhibition of ACE results in decreased plasma angiotensin IILabel. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretionLabel.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Decreased Blood Pressure', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Photosensitizing Agents', 'Protease Inhibitors']" +DB00790,Perindopril,"Perindoprilis an ACE inhibitor prodrug used to treat hypertension, mild to moderate congestive heart failure, and to reduce cardiovascular risk in patients with hypertension or post-myocardial infarction.","['P12821', 'Q6FHJ7']","Perindopril is a nonsulfhydryl prodrug that is metabolized via first pass effect (62%) and systemic hydrolysis (38%) to perindoprilat, its active metabolite, following oral administration. Perindoprilat lowers blood pressure by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of perindoprilat by causing increased vasodilation and decreased blood pressure.",[H][C@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O,"There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of ; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Perindoprilat, the active metabolite of perindopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Perindopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumansUSecreted frizzled-related protein inhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Alkanes', 'Amines', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Butanes', 'Cardiovascular Agents', 'Cholinesterase Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hydrocarbons, Acyclic', 'Hypotensive Agents', 'Indoles', 'Lipid Modifying Agents', 'Protease Inhibitors']" +DB00966,Telmisartan,"Telmisartanis an ARB used to treat hypertension, diabetic nephropathy, and congestive heart failure.","['P37231', 'P30556']","Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1receptor subtype. It has the highest affinity for the AT1receptor among commercially available ARBs and has minimal affinity for the AT2receptor.5New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials.3Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.2,5",CCCC1=NC2=C(C=C(C=C2C)C2=NC3=CC=CC=C3N2C)N1CC1=CC=C(C=C1)C1=CC=CC=C1C(O)=O,"Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels.Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators.TargetActionsOrganismAPeroxisome proliferator-activated receptor gammapartial agonistHumansAType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II receptor antagonists', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin II Type 1 Receptor Blockers', 'Angiotensin II Type 2 Receptor Blockers', 'Angiotensin Receptor Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'BCRP/ABCG2 Inhibitors', 'Benzene Derivatives', 'Benzimidazoles', 'Biphenyl Compounds', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'P-glycoprotein inhibitors', 'UGT1A3 substrates']" +DB09235,Efonidipine,"Efonidipine is a calcium channel blocker of thedihydropyridine class, commercialized by Shionogi & Co. (Japan). Initially, it was marketed in 1995 under the trade name,Landel. The drug has been shown to block T-type in addition to L-type calcium channels1,2. It has also been studied in atherosclerosis and acute renal failure2. This drug is also known as NZ-105, and several studies have been done on its pharmacokinetics in animals13.","['Q9P0X4', 'Q13936', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'Q06432', 'Q9Y698', 'O60359', 'Q9UBN1', 'Q9UF02', 'Q9BXT2', 'P62955', 'Q8WXS5', 'P54289', 'Q9NY47', 'Q8IZS8', 'Q7Z3S7', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'Q00975', 'O00555', 'Q15878', 'O43497', 'O95180', 'Q9P0X4', 'O43497', 'O95180', 'Q9P0X4', 'O43497', 'O95180']","Dihydropyridines (DHPs), act mainly on L-type calcium channels, essentially causing reflex tachycardia, which negatively affects cardiac function. This leads to a decrease in blood pressure and an increase in heart rate. Efonidipine acts on both L-type and T-type calcium channels. Because inhibition of T-type calcium channels in the sinoatrial (SA node) node attenuate reflex tachycardia, this drug favorably affects cardiac pacing. The effect of efonidipine on heart rate deserves special recognition with regard to reflex tachycardia, due to its unique effects in relation to other drugs in its class5.",CC1=C(C(C2=CC=CC(=C2)[N+]([O-])=O)C(=C(C)N1)P1(=O)OCC(C)(C)CO1)C(=O)OCCN(CC1=CC=CC=C1)C1=CC=CC=C1,"This drug inhibits the L-type and T-type calcium channels, thereby leading to vasodilation and decreased automaticity of the heart. Efonidipine exerts negative chronotropic effects, decreasing heart rate. Acting on SA node cells by inhibiting T-type calcium channel activity, Efonidipine prolongs the late phase- depolarization of the sinoatrial node action potential, decreasing heart rate. This is associated with decreased myocardial oxygen demand and increases of blood flow to the coronary arteries and thereby attenuates myocardial ischemia. Efonidipine increases glomerular filtration rate (GFR) without increasing intra-glomerular pressure and filtration fraction,,. This increase leads to the prevention of renal damage that is normally associated with hypertension.Efonidipine increases the rate of renal sodium excretion via the suppression of aldosterone synthesis and aldosterone secretion from the adrenal glands. Aldosterone-induced renal parenchymal fibrosis is said to be suppressed by efonidipine.L-type calcium channel blockers, such as efonidipine, preferentially dilate afferent arterioles in the kidney, whereas both L-/T-type and L-/N-type calcium channel blockers potently dilate both afferent and efferent arterioles. The distinct actions of calcium channel blockers on the renal microcirculation are demonstrated by changes in glomerular capillary pressure and subsequent renal injury: L-type calcium channel blockers favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. This supports the theory that L-Type/T-type calcium channel blockers may be of benefit in renal hypertension. Efonidipine is a long-acting medication due to a low dissociation constant.Recent studies suggest that efonidipine reduces plasma aldosterone levels in patients on regular hemodialysis, which is of additional benefit to the cardiovascular protection by antihypertensive therapy with efonidipine in patients with end-stage renal disease.TargetActionsOrganismUVoltage-dependent T-type calcium channel subunit alpha-IantagonistHumansUVoltage-dependent L-type calcium channel subunit alpha-CNot AvailableHumansAVoltage gated L-type calcium channelblockerHumansAVoltage-dependent calcium channelinhibitorHumansAVoltage-dependent T-type calcium channelinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Benzene Derivatives', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diuretics', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Nitro Compounds', 'Phenols', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB00575,Clonidine,"Clonidineis an alpha-2 adrenergic agonist used to treat hypertension and severe cancer pain, among other conditions, and to treat withdrawal symptoms from various substances. It is also used to aid in the diagnosis of pheochromocytoma and to prevent migraines.","['P18089', 'P18825', 'P08913', 'P35348', 'P35368', 'P25100']","Clonidine functions through agonism of alpha-2 adrenoceptors which have effects such as lowering blood pressure, sedation, and hyperpolarization of nerves.2It has a long duration of action as it is given twice daily and the therapeutic window is between 0.1mg and 2.4mg daily.8,9,10,11",ClC1=CC=CC(Cl)=C1NC1=NCCN1,"Clonidine is primarily an alpha- adrenoceptor agonist which causes central hypotensive and anti-arrhythmogenic effects.The alpha- adrenoceptor is coupled to the G-proteins Goand Gi.Giinhibits adenylyl cyclase and activates opening of a potassium channel that causes hyperpolarization.Clonidine binding to the alpha- adrenoceptor causes structural changes in the alpha subunit of the G-protein, reducing its affinity for GDP.Magnesium catalyzes the replacement of GDP with GTP.The alpha subunit dissociates from the other subunits and associates with an effector.The stimulation of alpha- adrenoceptors in the locus coeruleus may be responsible for the hypnotic effects of clonidine as this region of the brain helps regulate wakefulness.Clonidine can also decrease transmission of pain signals at the spine.Finally clonidine can affect regulators of blood pressure in the ventromedial and rostral-ventrolateral areas of the medulla.TargetActionsOrganismAAlpha-B adrenergic receptoragonistHumansAAlpha-C adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansUAlpha-A adrenergic receptoragonistHumansUAlpha-B adrenergic receptoragonistHumansUAlpha-D adrenergic receptoragonistHumans","['Smoking, Cessation']","['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Analgesics', 'Anesthetics', 'Anesthetics, General', 'Antiadrenergic Agents, Centrally Acting', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Antimigraine Preparations', 'Autonomic Agents', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Central alpha-2 Adrenergic Agonist', 'Central Alpha-agonists', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Imidazoles', 'Imidazoline Receptor Agonists', 'Imidazolines', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Sensory Organs', 'Sensory System Agents', 'Sympatholytics', 'Sympathomimetics in Glaucoma Therapy']" +DB00519,Trandolapril,"Trandolaprilis a prodrug of an ACE inhibitor used to treat hypertension, congestive heart failure, and to improve survival following a myocardial infarction.",['P12821'],"Trandolapril is the ethyl ester prodrug of a nonsulfhydryl ACE inhibitor, trandolaprilat. Trandolapril is deesterified in the liver to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE than its parent compound. ACE is a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure via a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of trandolaprilat by causing increased vasodilation and decreased blood pressure. The blood pressure lowering effect of trandolaprilat is due to a decrease in peripheral vascular resistance, which is not accompanied by significant changes in urinary excretion of chloride or potassium or water or sodium retention.",[H][C@@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC3=CC=CC=C3)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O,"There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of ; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Trandolaprilat, the active metabolite of trandolapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Trandolaprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Protease Inhibitors']" +DB00492,Fosinopril,"Fosinoprilis an ACE inhibitor used to treat mild to moderate hypertension, congestive heart failure, and to slow the progression of renal disease in hypertensive diabetics.",['P12821'],"Following oral administration, fosinopril is rapidly and completely hydrolyzed to its principle active metabolite, fosinoprilat. Hydrolysis is thought to occur in the gastrointestinal mucosa and liver. Fosinoprilat is a competitive inhibitor of ACE, a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of fosinoprilat by causing increased vasodilation and decreased blood pressure.",CCC(=O)O[C@@H](OP(=O)(CCCCC1=CC=CC=C1)CC(=O)N1C[C@@H](C[C@H]1C(O)=O)C1CCCCC1)C(C)C,"There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of ; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Fosinoprilat, the active metabolite of fosinopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Fosinoprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Amino Acids', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Imino Acids', 'Organophosphorus Compounds', 'Phosphinic Acids', 'Photosensitizing Agents', 'Protease Inhibitors']" +DB01054,Nitrendipine,Nitrendipineis a dihydropyridine calcium channel blocker indicated in the treatment of arterial hypertension.,"['Q13936', 'P54289', 'Q08289', 'Q01668', 'Q13698', 'Q9NY47', 'O95180', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555', 'Q12791', 'Q16558', 'Q9Y691', 'Q9NPA1', 'Q86W47', 'O15554', 'Q92952', 'Q9H2S1', 'Q9UGI6']","Nitrendipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nitrendipine is similar to other peripheral vasodilators. Nitrendipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.",CCOC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC,"By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nitrendipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansUVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansUVoltage-dependent L-type calcium channelinhibitorHumansUCalcium-activated potassium channelinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Substrates', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00925,Phenoxybenzamine,Phenoxybenzamineis an alpha adrenergic antagonist used to treat pheochromocytoma and episodes of hypertension and sweating.,"['P35348', 'P08913', 'P18825', 'P18089', 'P0DP23', 'P07550', 'P35368', 'P25100']","Phenoxybenzamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phenoxybenzamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain ""chemical sympathectomy"" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phenoxybenzamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phenoxybenzamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.",CC(COC1=CC=CC=C1)N(CCCl)CC1=CC=CC=C1,"Phenoxybenzamine produces its therapeutic actions by blocking alpha receptors, leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansAAlpha-A adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUCalmodulininhibitorHumansUBeta- adrenergic receptorNot AvailableHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Amines', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Ethylamines', 'Hypotensive Agents', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Peripheral alpha-1 blockers', 'Peripheral Vasodilators', 'Vasodilating Agents']" +DB01275,Hydralazine,"Hydralazineis an antihypertensive agent used for the management of essential hypertension or severe hypertension associated with conditions requiring immediate action, heart failure, and pre-eclampsia or eclampsia .","['Q16853', 'Q16665', 'P13674']","Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure.19Hydralazine has a short duration of action of 2-6h.10This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg.19Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.19",NNC1=NN=CC2=CC=CC=C12,"Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure.,The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions.This decrease in vascular resistance leads to increased heart rate, stroke volume, and cardiac output.Hydralazine also competes with protocollagen prolyl hydroxylase (CPH) for free iron.This competition inhibits CPH mediated hydroxylation of HIF-α, preventing the degradation of HIF-α.Induction of HIF-α and VEGF promote proliferation of endothelial cells and angiogenesis.TargetActionsOrganismAMembrane primary amine oxidaseinhibitorHumansUHypoxia-inducible factor -alphainducerHumansUProlyl -hydroxylase subunit alpha-inhibitorHumans",[],"['Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Arteriolar Smooth Muscle, Agents Acting On', 'Arteriolar Vasodilation', 'Arteriolar Vasodilator', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Direct Vasodilators', 'Drugs that are Mainly Renally Excreted', 'Hydrazinophthalazine Derivatives', 'Hydrazinophthalazine Derivatives and Diuretics', 'Hypotensive Agents', 'Phthalazines', 'Pyridazines', 'Vasodilating Agents']" +DB01340,Cilazapril,Cilazaprilis an ACE inhibitor used for the management of hypertension and heart failure.,['P12821'],"Cilazapril inhibits the production angiotensin II. By doing so, it decreases sodium and water reabsorption (via aldosterone) and it decreases vasoconstriction. The combined effect of this is a decrease in vascular resistance, and therefore, blood pressure. The absolute bioavailability of cilazaprilat after oral administration of cilazapril is 57% based on urinary recovery data. (The absolute bioavailability of cilazaprilat after oral administration of cilazaprilat is 19%.) Ingestion of food immediately before the administration of cilazapril reduces the average peak plasma concentration of cilazaprilat by 29%, delays the peak by one hour and reduces the bioavailability of cilazaprilat by 14%. These pharmacokinetic changes have little influence on plasma ACE inhibition.",CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O,"Cilazapril is a pyridazine ACE inhibitor. It competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Enzyme Inhibitors', 'Hypotensive Agents', 'P-glycoprotein inhibitors', 'Protease Inhibitors', 'Pyridazines']" +DB00590,Doxazosin,Doxazosinis an alpha-1 adrenergic receptor used to treat mild to moderate hypertension and urinary obstruction due to benign prostatic hyperplasia.,"['P35348', 'P25100', 'Q12809', 'Q9H252', 'Q9NS40', 'P35368']","Doxazosin decreases standing and supine blood pressure5and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. +Doxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses. Treatment should be started with the 1 mg dose of doxazosin, followed by slow titration to the appropriate dose.19Patients must be advised of this risk and to avoid situations in which syncope and dizziness could be hazardous following the ingestion of doxazosin.19Interestingly doxazosin exerts beneficial effects on plasma lipids. It reduces LDL (low-density lipoprotein) cholesterol and triglyceride levels and increases HDL (high-density lipoprotein) cholesterol levels.5A note on priapism riskIn rare cases, doxazosin and other alpha-1 blockers may cause priapism, a painful occurrence of persistent and unrelievable penile erection that can lead to impotence if medical attention is not sought as soon as possible. Patients must be advised of the priapism risk associated with doxazosin and to seek medical attention immediately if it is suspected.9,19",COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1COC2=CC=CC=C2O1,"Doxazosin selectively inhibits the postsynaptic alpha- receptors on vascular smooth muscle by nonselectively blocking the alpha-a, alpha-b, and alpha-d subtypes,. This action on blood vessels decreases systemic peripheral vascular resistance, reducing blood pressure, exerting minimal effects on the heart rate due to its receptor selectivity.,Norepinephrine-activated alpha- receptors located on the prostate gland and bladder neck normally cause contraction of regional muscular tissue, obstructing urinary flow and contributing to the symptoms of benign prostatic hypertrophy. Alpha- antagonism causes smooth muscle relaxation in the prostate and bladder, effectively relieving urinary frequency, urgency, weak urinary stream, and other unpleasant effects of BPH.Recently, doxazosin was found to cause apoptosis of hERG potassium channels in an in vitro setting, possibly contributing to a risk of heart failure with doxazosin use.,,TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansAAlpha-D adrenergic receptorantagonistHumansUHERG human cardiac K+ channelinhibitorHumansUAlpha-B adrenergic receptorNot AvailableHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Antiadrenergic Agents, Peripherally Acting', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Drugs Used in Benign Prostatic Hypertrophy', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'P-glycoprotein inhibitors', 'Peripheral alpha-1 blockers', 'Quinazolines', 'Urologicals']" +DB00806,Pentoxifylline,Pentoxifyllineis a methylxanthine derivative used to treat intermittent claudication caused by chronic occlusive arterial disease of the limbs.,"['P29274', 'P30542', 'P21589']","Pentoxifylline, a synthetic dimethylxanthine derivative structurally related totheophyllineandcaffeine, exhibits hemorheological, anti-oxidative, and anti-inflammatory properties and is traditionally indicated in the treatment of peripheral arterial disease (PAD). In PAD patients with concurrent cerebrovascular and coronary artery diseases, pentoxifylline treatment has occasionally been associated with angina, arrhythmia, and hypotension. Concurrent use withwarfarinshould be associated with more frequent monitoring of prothrombin times. Also, patients with risk factors complicated by hemorrhages, such as retinal bleeding, peptic ulceration, and recent surgery, should be monitored periodically for bleeding signs.29",CN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C,"Patients with peripheral arterial disease (PAD) may suffer from intermittent claudication, exertional leg pain that resolves upon rest, which is underscored by a complex etiology including vascular dysfunction (reduced limb perfusion, angiogenesis, and microcirculatory flow), systemic inflammation, and skeletal muscle dysfunction.Pentoxifylline (PTX), (,-dimethyl--(-oxohexyl)-,-dihydro-H-purine-,-dione) or -(-oxohexyl)-,-­dimethylxanthine, is a methyl-xanthine derivative that acts to lower blood viscosity by increasing erythrocyte flexibility, reducing plasma fibrinogen, inhibiting neutrophil activation, and suppressing erythrocyte/platelet aggregation; it also has antioxidant and anti-inflammatory effects.,Although the precise mechanism of action has yet to be elucidated, numerous studies have suggested several effects of PTX.The classical interpretation of PTX's broad effects is due to its ability to act,in vitro, as a non-specific cyclic-','-phosphodiesterase (PDE) inhibitor at millimolar concentrations; specifically, it has been proposed that inhibition of PDE type III and IV isozymes leads to elevated cyclic adenosine monophosphate (cAMP) levels, which mediate diverse downstream effects.,,This view has been challenged, specifically by observing those plasma concentrations of PTX in routine clinical use are typically only around μM, far lower than those used to inhibit PDEsin vitro.Instead, several studies have suggested that PTX can modulate adenosine receptor function, specifically the Gα-coupled AA receptor (AAR). Whether PTX acts directly as an AAR agonist is unclear, although it can clearly increase the response of AAR to adenosine.,,,AAR activation activates adenylyl cyclase, which increases intracellular cAMP levels; this observation may explain PTX's ability to increase intracellular cAMP in a PDE-independent fashion.Elevated cAMP levels have numerous downstream effects. cAMP-mediated activation of protein kinase A (PKA) suppresses nuclear translocation of NF-κB, which suppresses transcription of pro-inflammatory cytokines such as tumour necrosis factor (TNF-α), interleukin- (IL-), and IL- as well as TNF-induced molecules such as adhesion molecules (ICAM and VCAM) and the C-reactive protein (CRP).,,,PTX has also been shown to prevent the downstream phosphorylation of p MAPK and ERK, which are responsible for assembling the NADPH oxidase involved in the neutrophil oxidative burst. This effect is due to a PKA-independent decrease in Akt phosphorylation and a PKA-dependent decrease in phosphorylation of p MAPK and ERK.,,This transcriptional regulation at least partially explains the anti-inflammatory and anti-oxidative properties of PTX.Also, activated PKA can activate the cAMP response element-binding protein (CREB), which itself blocks SMAD-driven gene transcription, effectively disrupting transforming growth factor (TGF-β) signalling.,This results in lower levels of fibrinogenic molecules such as collagens, fibronectin, connective tissue growth factor, and alpha-smooth muscle actin.,,,Hence, disruption of TGF-β signalling may explain the anti-fibrotic effects of PTX, including at least some of the decrease in blood viscosity.The picture is complicated by the observation that PTX metabolites M, M, and M have been shown to inhibit C Des Arg- and formyl-methionylleucylphenylalanine-induced superoxide production in neutrophils and M and M significantly contribute to PTX's observed hemorheological effects.,,Overall, PTX administration is associated with decreased pro-inflammatory molecules, an increase in anti-inflammatory molecules such as IL-, and decreased production of fibrinogenic and cellular adhesion molecules.TargetActionsOrganismAAdenosine receptor AaagonistHumansAPhosphodiesterase enzymesinhibitorHumansUAdenosine receptor ANot AvailableHumansU'-nucleotidaseinhibitorHumans",[],"['Alkaloids', 'Antioxidants', 'Antiplatelet agents', 'Blood Viscosity Reducer', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Free Radical Scavengers', 'Hematologic Activity Alteration', 'Hematologic Agents', 'Hemorrheologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Peripheral Vasodilators', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Protective Agents', 'Purine Derivatives', 'Purines', 'Purinones', 'Radiation-Protective Agents', 'Vasodilating Agents', 'Xanthine derivatives']" +DB01029,Irbesartan,"Irbesartanis an angiotensin receptor blocker used to treat hypertension, delay progression of diabetic nephropathy, and treat congestive heart failure.","['P30556', 'P05412']","Irbesartan is an angiotensin receptor blocker used to treat hypertension and diabetic nephropathy.7,8It has a long duration of action as it is usually taken once daily and a wide therapeutic index as doses may be as low as 150mg daily but doses of 900mg/day were well tolerated in healthy human subjects.7,8,5",CCCCC1=NC2(CCCC2)C(=O)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1,"Irbesartan prevents angiotensin II binding to the ATreceptor in tissues like vascular smooth muscle and the adrenal gland.,Irbesartan and its active metabolite bind the ATreceptor with times more affinity than they bind to the ATreceptor.,Irbesartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation and prevents the secretion of aldosterone, lowering blood pressure.,Angiotensin II would otherwise bind to the ATreceptor, inducing vasoconstriction and aldosterone secretion, raising blood pressure.,TargetActionsOrganismAType- angiotensin II receptorantagonistHumansUTranscription factor AP-other/unknownHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing hyperkalemia', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II receptor antagonists', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin II Type 2 Receptor Blockers', 'Angiotensin Receptor Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzene Derivatives', 'Biphenyl Compounds', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Spiro Compounds', 'Tetrazoles', 'UGT1A3 substrates']" +DB00275,Olmesartan,Olmesartanis an angiotensin receptor blocker (ARB) used in the treatment of hypertension.,['P30556'],"Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium.Hypotension in Volume- or Salt-Depleted PatientsIn patients with an activated renin-angiotensin aldosterone system, such as volume-and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may be anticipated after initiation of treatment with olmesartan. Initiate treatment under close medical supervision. If hypotension does occur, place the patient in the supine position and, if necessary, give an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.23,24Valvular Stenosis: there is concern on theoretical grounds that patients with aortic stenosis might be at a particular risk of decreased coronary perfusion, because they do not develop as much afterload reduction.24Impaired Renal FunctionAs a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals treated with olmesartan. In patients whose renal function may depend upon the activity of the renin-angiotensin- aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. Similar results may be anticipated in patients treated with olmesartan.In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.23,24Sprue-like EnteropathySevere, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan, exclude other etiologies. Consider discontinuation of olmesartan medoxomil in cases where no other etiology is identified.23,24Electrolyte ImbalancesOlmesartan medoxomil contains olmesartan, a drug that inhibits the renin-angiotensin system (RAS). Drugs that inhibit the RAS can cause hyperkalemia. Monitor serum electrolytes periodically.23,24",CCCC1=NC(=C(N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1)C(O)=O)C(C)(C)O,"Olmesartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which also includestelmisartan,candesartan,losartan,valsartan, andirbesartan. ARBs selectively bind to angiotensin receptor (AT) and prevent the protein angiotensin II from binding and exerting its hypertensive effects. As the principal pressor agent of the renin-angiotensin system, Angiotensin II causes vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis.Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium.Olmesartan also effects on the renin-angiotensin aldosterone system (RAAS) plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via AT receptor blockade inhibits negative regulatory feedback within RAAS, which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and preventing ventricular hypertrophy and remodelling.TargetActionsOrganismAType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing hyperkalemia', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II Antagonists and Calcium Channel Blockers', 'Angiotensin II receptor antagonists', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin Receptor Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'BSEP/ABCB11 Inhibitors', 'Cardiovascular Agents', 'Hypotensive Agents', 'Imidazoles', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'Tetrazoles']" +DB00999,Hydrochlorothiazide,"Hydrochlorothiazideis a thiazide diuretic used to treat edema associated with a number of conditions, and hypertension.","['P55017', 'Q12791']","Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine.2,3,4,10,11Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg.10,11Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.10,11",NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1,"Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT, OAT, and OAT.,From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein (MRP).Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family Member (SLCA).,,Inhibition of SLCA reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.TargetActionsOrganismASolute carrier family member inhibitorHumansACalcium-activated potassium channel subunit alpha-inhibitorHumans",[],"['Amides', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzothiadiazines', 'Cardiovascular Agents', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis', 'Low-Ceiling Diuretics and Potassium-Sparing Agents', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Nephrotoxic agents', 'Non Potassium Sparing Diuretics', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Substrates', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB00659,Acamprosate,Acamprosateis a medication used to maintain alcohol abstinence in patients with alcohol dependence.,"['Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'P41594', 'Q9UBS5']","Acamprosate acts on the CNS, aiding in the restoration of normal glutaminergic neuron activity.1Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcohol-dependent individuals, likely through effects on NMDA receptors and calcium channels.7It is a safe and well-tolerated drug for patients with alcohol dependency and improves the likelihood of alcohol abstinence.1,12",CC(=O)NCCCS(O)(=O)=O,"The mechanism of action of acamprosate for the maintenance of alcohol abstinence has not been established. Chronic alcohol exposure is believed to modify the balance between neuronal excitation and inhibition. Results of studies in animals suggest acamprosate may interact with glutamate and GABA neurotransmitter systems in the CNS, supporting the hypothesis that acamprosate restores the balance between neuronal excitation and inhibition.,Evidence shows that acamprosate directly binds and inhibits GABA B receptors and indirectly affects GABA A receptors.,TargetActionsOrganismAGlutamate (NMDA) receptorantagonistHumansAMetabotropic glutamate receptor antagonistHumansAGamma-aminobutyric acid type B receptor subunit inhibitorHumans",[],"['Alcohol Deterrents', 'Central Nervous System Agents', 'Drugs Used in Addictive Disorders', 'Drugs Used in Alcohol Dependence', 'Hydrocarbons, Acyclic', 'Miscellaneous Central Nervous System Agents', 'Nervous System', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Substrates', 'Sulfonic Acids', 'Sulfur Acids', 'Sulfur Compounds']" +DB01392,Yohimbine,Yohimbineis an alpha-2-adrenergic blocker and sympatholytic found in supplements used to.,"['P08913', 'P18089', 'P18825', 'P08908', 'P28222', 'P28221', 'P14416', 'P35462', 'P28223', 'P28335', 'P48048', 'P78508', 'Q14654', 'Q14500', 'Q9UNX9', 'Q99712', 'Q15842', 'P41595']","Yohimbine is an indolalkylamine alkaloid with chemical similarity to reserpine. Yohimbine blocks presynaptic alpha-2 adrenergic receptors. Its action on peripheral blood vessels resembles that of reserpine, though it is weaker and of short duration. Yohimbine's peripheral autonomic nervous system effect is to increase parasympathetic (cholinergic) and decrease sympathetic (adrenergic) activity. It is to be noted that in male sexual performance, erection is linked to cholinergic activity and to alpha-2 adrenergic blockade which may theoretically result in increased penile inflow, decreased penile outflow or both. Yohimbine exerts a stimulating action on the mood and may increase anxiety. Such actions have not been adequately studied or related to dosage although they appear to require high doses of the drug. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly Yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage.",[H][C@@]12CC[C@H](O)[C@H](C(=O)OC)[C@@]1([H])C[C@]1([H])N(CCC3=C1NC1=CC=CC=C31)C2,"Yohimbine is a pre-synaptic alpha -adrenergic blocking agent. The exact mechanism for its use in impotence has not been fully elucidated. However, yohimbine may exert its beneficial effect on erectile ability through blockade of central alpha -adrenergic receptors producing an increase in sympathetic drive secondary to an increase in norepinephrine release and in firing rate of cells in the brain noradrenergic nuclei. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAAlpha-C adrenergic receptorantagonistHumansU-hydroxytryptamine receptor Apartial agonistHumansU-hydroxytryptamine receptor Bpartial agonistHumansU-hydroxytryptamine receptor Dpartial agonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUATP-sensitive potassium channelinhibitorHumansU-hydroxytryptamine receptor BantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-2 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Alkaloids', 'Antidepressive Agents', 'Autonomic Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs Used in Erectile Dysfunction', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Mydriatics', 'Neurotransmitter Agents', 'Other Miscellaneous Therapeutic Agents', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Secologanin Tryptamine Alkaloids', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1D Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Urological Agents', 'Urologicals']" +DB00230,Pregabalin,"Pregabalinis an anticonvulsant drug used to treat neuropathic pain conditions and fibromyalgia, and for the treatment of partial onset seizures in combination with other anticonvulsants.",['P54289'],"Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors.620Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system.620Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.20",CC(C)C[C@H](CN)CC(O)=O,"Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models.By binding presynaptically to the alpha-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide.In addition, pregabalin prevents the alpha-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action.Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.TargetActionsOrganismAVoltage-dependent calcium channel subunit alpha-/delta-Not AvailableHumans",[],"['Acids, Acyclic', 'Agents causing angioedema', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Aminobutyrates', 'Analgesics', 'Anti-Anxiety Agents', 'Anticonvulsants', 'Bradycardia-Causing Agents', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Gabapentinoids', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Miscellaneous Anticonvulsants', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Sensory System Agents', 'Tranquilizing Agents', 'Vasodilating Agents']" +DB00704,Naltrexone,Naltrexoneis a narcotic antagonist used in opioid overdose.,"['P35372', 'P41145', 'P41143', 'Q99720']","Naltrexone, a pure opioid antagonist, is a synthetic congener of oxymorphone with no opioid agonist properties. Naltrexone is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. When co-administered with morphine, on a chronic basis, naltrexone blocks the physical dependence to morphine, heroin and other opioids. In subjects physically dependent on opioids, naltrexone will precipitate withdrawal symptomatology.",[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(CC3CC3)[C@]([H])(C4)[C@]1(O)CCC2=O,"Naltrexone is a pure opiate antagonist and has little or no agonist activity. The mechanism of action of naltrexone in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone is thought to act as a competitive antagonist at mc, κ, and δ receptors in the CNS, with the highest affintiy for the μ receptor. Naltrexone competitively binds to such receptors and may block the effects of endogenous opioids. This leads to the antagonization of most of the subjective and objective effects of opiates, including respiratory depression, miosis, euphoria, and drug craving. The major metabolite of naltrexone, -β-naltrexol, is also an opiate antagonist and may contribute to the antagonistic activity of the drug.TargetActionsOrganismAMu-type opioid receptorantagonistHumansAKappa-type opioid receptorantagonistHumansADelta-type opioid receptorantagonistHumansUSigma non-opioid intracellular receptor Not AvailableHumans",[],"['Agents Causing Muscle Toxicity', 'Alcohol Deterrents', 'Alimentary Tract and Metabolism', 'Alkaloids', 'Analgesics', 'Antiobesity Preparations, Excl. Diet Products', 'Central Nervous System Agents', 'Centrally Acting Antiobesity Products', 'Drugs Used in Addictive Disorders', 'Drugs Used in Alcohol Dependence', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Natural Opium Alkaloids', 'Nervous System', 'Opiate Alkaloids', 'Opiate Antagonists', 'Opioid Antagonists', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'UGT1A1 Substrates']" +DB06155,Rimonabant,"Rimonabant is an anorectic anti-obesity drug produced and marketed by Sanofi-Aventis. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite. Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. Rimonabant is approved in 38 countries including the E.U., Mexico, and Brazil. It was rejected for approval for use in the United States. This decision was made after a U.S. advisory panel recommended the medicine not be approved because it may increase suicidal thinking and depression.","['P21554', 'Q9Y2T6']","In the RIO-North America trial, 3040 patients were randomized to receive either placebo or one of two doses of rimonabant (5 mg or 20 mg per day). Patients taking 20 mg rimonabant had significant weigh loss, decrease in waist circumference, improved insulin sensitivity, and increases in HDL cholesterol, compared to patients on placebo.",CC1=C(N(N=C1C(=O)NN1CCCCC1)C1=C(Cl)C=C(Cl)C=C1)C1=CC=C(Cl)C=C1,"Rimonabant is a specific CB cannabinoid receptor antagonist. There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviours. It is therefore reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders.TargetActionsOrganismACannabinoid receptor antagonistHumansUG-protein coupled receptor Not AvailableHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Anti-Obesity Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Cannabinoid Receptor Antagonists', 'Cannabinoids and similars', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Neurotransmitter Agents', 'Piperidines', 'Pyrazoles', 'Receptor, Cannabinoid, CB1, antagonists & inhibitors']" +DB00657,Mecamylamine,Mecamylamineis a nicotine antagonist used to treat moderate to severe essential hypertension and uncomplicated malignant hypertension.,"['Q15822', 'P36544', 'P43681', 'P17787']","Mecamylamine is a potent, oral antihypertensive agent and ganglion blocker, and is a secondary amine. Mecamylamine is indicated for the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. Mecamylamine reduces blood pressure in both normotensive and hypertensive individuals. A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this antihypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced. Mecamylamine crosses the blood-brain and placental barriers.",CNC1(C)C2CCC(C2)C1(C)C,"Mecamylamine is a ganglionic blocker which prevents stimulation of postsynaptic receptors by acetylcholine released from presynaptic nerve endings. The hypotensive effect of Mecamylamine is attributed to reduction in sympathetic tone, vasodilation, and reduced cardiac output, and is primarily postural.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Antiadrenergic Agents, Ganglion-Blocking', 'Anticholinergic Agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Bridged-Ring Compounds', 'Cardiovascular Agents', 'Cholinergic Agents', 'Decreased Autonomic Ganglionic Activity', 'Drugs that are Mainly Renally Excreted', 'Ganglion Blockers', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Norbornanes', 'Peripheral Nervous System Agents', 'Secondary and Tertiary Amines']" +DB00776,Oxcarbazepine,Oxcarbazepineis an anti-epileptic used in the treatment of partial-onset seizures.,"['P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q07699', 'O60939', 'Q9NY72', 'Q8IWT1']","Oxcarbazepine is an anticonvulsant drug that reduces the incidence of seizures in epilepsy by inhibiting abnormal electrical activity in the brain.10,11,12There have been rare reports of oxcarbazepine resulting in the development of hematologic abnormalities, including agranulocytosis and aplastic anemia. Patients should be undergo frequent laboratory testing and should be monitored closely for signs and symptoms of blood dyscrasias. Oxcarbazepine has also been associated with the development of dermatologic reactions which can progress from a simple rash to potentially fatal reactions such as toxic epidermal necrolysis (TEN) or Stevens-Johnson Syndrome (SJS). Patients with the HLA-A 3101 and/or HLA-B 1502 alleles may be at higher risk of this reaction. Oxcarbazepine should be discontinued at the first sign of a drug-induced skin reaction.10,11,12",NC(=O)N1C2=CC=CC=C2CC(=O)C2=C1C=CC=C2,"The exact mechanism through which oxcarbazepine and its active metaoblite, MHD, exert their anti-epileptic effects is unclear, but is thought to primarily involve the blockade of voltage-gated sodium channels.,,,The opening and closing of sodium channels allows for the propagation of action potentials along neurons - in epilepsy, these action potentials can occur in excess of that required for normal function, and the repetitive and pathological firing of these action potentials leads to seizure activity. Both oxcarbazepine and MHD are thought to inhibit seizure activity by binding to the inactive state of voltage-gated sodium channels, thus prolonging the period in which the receptor is unavailable for action potential propagation.This helps to stabilize hyperexcited neuronal membranes, inhibit repetitive neuron firing, and prevent the spread of seizure activity within the CNS without affecting normal neuronal transmission.,,Increased potassium conductance and modulation of voltage-activated calcium channels is also thought to play a role in the anti-seizure activity of oxcarbazepine.,,Inhibition of glutamatergic activity was thought to contribute to oxcarbazepine's activity, but this effect could not be replicatedin vivo.TargetActionsOrganismUSodium channel proteininhibitorHumans",['Monotherapy'],"['Anti-epileptic Agent', 'Anticonvulsants', 'Carboxamide Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Dibenzazepines', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inducing Antiepileptic Drugs', 'Heterocyclic Compounds, Fused-Ring', 'Membrane Transport Modulators', 'Miscellaneous Anticonvulsants', 'Nervous System', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB06230,Nalmefene,Nalmefeneis an opioid antagonist used to reduce alcohol consumption in adults with alcohol dependence and treat and prevent opioid overdose.,"['P41145', 'P41143', 'P35372']","Nalmefene is an opioid antagonist with no agonist activity. It works to prevent or reverse the effects of opioids, including respiratory depression, sedation, and hypotension.8Nalmefene has a longer duration of action thannaloxone, another opioid antagonist used to reverse opioid overdose.2,8In a study of brain receptor occupancy, a 1 mg dose of nalmefene blocked over 80% of brain opioid receptors within five minutes after administration.8Nalmefene has no opioid agonist activity and it is not associated with drug tolerance, physical dependence, or abuse potential.8Nalmefene is not known to produce respiratory depression, psychotomimetic effects, or pupillary constriction. No pharmacological activity was observed when nalmefene was administered in the absence of opioid agonists. However, as with all opioid antagonists, nalmefene can produce acute withdrawal symptoms in individuals with opioid dependence. These withdrawal symptoms should be managed with symptomatic and supportive treatment: the administration of large amounts of opioids to patients receiving opioid antagonists in an attempt to overcome a full blockade has resulted in adverse respiratory and circulatory reactions.8",OC1=CC=C2C[C@H]3N(CC4CC4)CC[C@@]45[C@@H](OC1=C24)C(=C)CC[C@@]35O,"The opioid system consists of three opioid receptors - mu (μ), delta (δ), and kappa (κ) - that are G-protein coupled receptors.Opioid receptors are activated by endogenous opioid peptides and are expressed throughout the brain to play a critical role in mood regulation, pain, reward, addictive behaviours, and substance use disorders. Opioid receptors are involved in various brain signalling pathways, including the mesolimbic pathway, sometimes referred to as the reward pathway. The mesolimbic pathway plays an important role in the positive reinforcement of natural rewards like food and drugs of abuse like exogenous opioid drugs. Many abused drugs activate mu-opioid receptors, leading to positive reinforcing effects.Alcohol consumption can also cause the release of endogenous opioids, which bind to mu and delta receptors, thereby increasing the release of dopamine in the nucleus accumbens to induce reward and positive reinforcement effects.Nalmefene is an antagonist at the mu and delta-opioid receptors and a partial agonist at the kappa-opioid receptor. As an antagonist, nalmefene blocks ligands from binding to the opioid receptor.Animal studies suggest that kappa-opioid receptor signalling blocks acute reward and positive reinforcement effects of drugs with abusive potential by decreasing dopamine in the nucleus accumbens.In vivostudies have demonstrated that nalmefene reduces alcohol consumption, possibly by modulating cortico-mesolimbic functions.Preclinical studies suggest that nalmefene restores alcohol-induced dysregulations of the MOR/endorphins and the KOR/dynorphin system.TargetActionsOrganismAKappa-type opioid receptorpartial agonistHumansADelta-type opioid receptorantagonistHumansAMu-type opioid receptorantagonistHumans",[],"['Alkaloids', 'Antidotes', 'Antipruritics', 'Central Nervous System Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Addictive Disorders', 'Drugs Used in Alcohol Dependence', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Nervous System', 'Opiate Alkaloids', 'Opioid Antagonists', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB01454,Midomafetamine,"An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems.","['Q05940', 'P23975', 'P31645', 'Q01959', 'P28223', 'P41595', 'P28335']","MDMA acts as a releasing agent of serotonin, norepinephrine, and dopamine.",CNC(C)CC1=CC2=C(OCO2)C=C1,"It enters neurons via carriage by the monoamine transporters. Once inside, MDMA inhibits the vesicular monoamine transporter, which results in increased concentrations of serotonin, norepinephrine, and dopamine into the cytoplasm, and induces their release by reversing their respective transporters through a process known as phosphorylation. It also acts as a weak -HT and -HT receptor agonist. +MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin secretion via activation of the serotonin system. Oxytocin is a hormone released following events like hugging, orgasm, and childbirth, and is thought to facilitate bonding and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin -HTA receptor.TargetActionsOrganismASynaptic vesicular amine transporterinhibitorHumansASodium-dependent noradrenaline transporternegative modulatorHumansASodium-dependent serotonin transporternegative modulatorHumansUSodium-dependent dopamine transporternegative modulatorHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor CagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Amphetamines', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Ethylamines', 'Hallucinogens', 'Membrane Transport Modulators', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Phenethylamines', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Sympathomimetics']" +DB01238,Aripiprazole,"Aripiprazoleis an atypical antipsychotic used in the treatment of a wide variety of mood and psychotic disorders, such as schizophrenia, bipolar I, major depressive disorder, irritability associated with autism, and Tourette's syndrome.","['P14416', 'P28223', 'P08908', 'P35348', 'P35368', 'P35462', 'P28221', 'P34969', 'P08913', 'P18825', 'P35367', 'P28222', 'P28335', 'P46098', 'P50406', 'P21728', 'P21917', 'P18089', 'P28566', 'P21918', 'P41595', 'P47898', 'P08588', 'P07550', 'P25021', 'Q9Y5N1', 'Q9H3N8', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P41145', 'P35372', 'P41143', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'Q01959', 'P31645']","Aripiprazole exhibits high affinity for dopamine D2and D3, serotonin 5-HT1aand 5-HT2areceptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2cand 5-HT7, alpha1-adrenergic and histamine H1receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).8",ClC1=CC=CC(N2CCN(CCCCOC3=CC4=C(CCC(=O)N4)C=C3)CC2)=C1Cl,"The antipsychotic action of aripiprazole is likely due to its partial agonist activity on D and -HTAreceptors as well as its antagonist activity at -HTAreceptors; however, the exact mechanism has not been fully elucidated.,One of the mechanisms that have been proposed is that aripiprazole both stimulates and inhibits dopamine as it engages the D receptor. It lowers dopamine neuronal firing at high dopamine concentrations and increases dopamine firing at low concentrations. Its partial agonist activity gives aripiprazole an intermediate level of dopaminergic neuronal tone between full agonist and antagonist of the D receptor.In addition, some adverse effects may be due to action on other receptors.[L] For example, orthostatic hypotension may be explained by antagonism of the adrenergic alpha- receptors.TargetActionsOrganismADopamine D receptorantagonistpartial agonistHumansA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor Apartial agonistHumansNAlpha-A adrenergic receptorantagonistHumansNAlpha-B adrenergic receptorantagonistHumansUDopamine D receptorantagonistpartial agonistHumansU-hydroxytryptamine receptor DantagonistligandHumansU-hydroxytryptamine receptor antagonistpartial agonistHumansNAlpha-A adrenergic receptorantagonistHumansNAlpha-C adrenergic receptorantagonistother/unknownHumansNHistamine H receptorantagonistHumansU-hydroxytryptamine receptor BantagonistligandHumansU-hydroxytryptamine receptor Cantagonistpartial agonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor antagonistHumansUDopamine D receptorantagonistpartial agonistligandHumansUDopamine D receptorantagonistpartial agonistHumansNAlpha-B adrenergic receptorantagonistligandHumansU-hydroxytryptamine receptor EantagonistligandHumansUDopamine D receptorantagonistpartial agonistligandHumansU-hydroxytryptamine receptor Binverse agonistHumansU-hydroxytryptamine receptor AligandHumansUBeta- adrenergic receptorligandHumansUBeta- adrenergic receptorligandHumansUHistamine H receptorligandHumansUHistamine H receptorligandHumansUHistamine H receptorligandHumansUMuscarinic acetylcholine receptor MligandHumansUMuscarinic acetylcholine receptor MligandHumansUMuscarinic acetylcholine receptor MligandHumansUMuscarinic acetylcholine receptor MligandHumansUMuscarinic acetylcholine receptor MligandHumansUKappa-type opioid receptorligandHumansUMu-type opioid receptorligandHumansUDelta-type opioid receptorligandHumansUGlutamate (NMDA) receptorligandHumansUSodium-dependent dopamine transportermodulatorHumansUSodium-dependent serotonin transportermodulatorHumans",['Monotherapy'],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Aripiprazole and prodrugs', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Piperazines', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'QTc shortening agents', 'Quinolines', 'Quinolones', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1D Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB01273,Varenicline,Vareniclineis a partial agonist at nicotinic acetylcholine receptors used as an aid in smoking cessation.,"['P43681', 'P36544', 'P32297', 'Q15825', 'P17787']","Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.",C1C2CNCC1C1=C2C=C2N=CC=NC2=C1,"Varenicline is an alpha- beta- neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectivity for this receptor subclass, relative to other nicotinic receptors (>-fold alpha- beta-, >-fold alpha-, >,-fold alpha- beta gamma delta) or non-nicotinic receptors and transporters (>-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha- beta- receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-partial agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-partial agonistHumansUNeuronal acetylcholine receptor subunit alpha-partial agonistHumansUNeuronal acetylcholine receptor subunit beta-partial agonistHumans","['Smoking, Cessation']","['Benzazepines', 'Cholinergic Agents', 'Cholinergic Agonists', 'Cholinergic Receptor Agonist', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Addictive Disorders', 'Drugs Used in Nicotine Dependence', 'Heterocyclic Compounds, Fused-Ring', 'Miscellaneous Autonomic Drugs', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Agonists', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Ophthalmologicals', 'Partial Cholinergic Nicotinic Agonist', 'Partial Cholinergic Nicotinic Agonists', 'Quinoxalines', 'Sensory Organs', 'Smoking Cessation Agents']" +DB00524,Metolazone,Metolazoneis a thiazide-like diuretic used to treat hypertension.,['P55017'],"Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.",CC1NC2=CC(Cl)=C(C=C2C(=O)N1C1=CC=CC=C1C)S(N)(=O)=O,The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.TargetActionsOrganismASolute carrier family member inhibitorHumans,[],"['Amides', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Diuretics', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis', 'Low-Ceiling Diuretics and Potassium-Sparing Agents', 'Low-Ceiling Diuretics, Excl. Thiazides', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Non Potassium Sparing Diuretics', 'Quinazolines', 'Quinazolinones', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazide-like Diuretic']" +DB00797,Tolazoline,Tolazolineis a vasodilator used to treat pulmonary artery anomalies.,"['P35348', 'P08913', 'P35367', 'P25021', 'P18825', 'P18089']",Tolazoline is a pulmonary vasodilator indicated used to decrease pulmonary vascular resistance (PVR) in persistent pulmonary hypertension of the newborn (PPHN).,C(C1=NCCN1)C1=CC=CC=C1,"Vasodilation by means of a direct effect on peripheral vascular smooth muscle and indirect effects produced, in part, by release of endogenous histamine; tolazoline has moderate alpha-adrenergic blocking activity and has histamine agonist activity. Tolazoline usually reduces pulmonary arterial pressure and vascular resistance.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUHistamine H receptoragonistHumansUHistamine H receptoragonistHumansUAlpha-C adrenergic receptorbinderHumansUAlpha-B adrenergic receptorbinderHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Hypotensive Agents', 'Imidazoles', 'Imidazoline Derivatives', 'Imidazolines', 'Musculo-Skeletal System', 'Neurotransmitter Agents', 'Peripheral alpha-1 blockers', 'Peripheral Vasodilators', 'Topical Products for Joint and Muscular Pain', 'Vasodilating Agents']" +DB00561,Doxapram,Doxapramis a short acting respiratory stimulant used to treat acute respiratory insufficiency in COPD patients.,"['O14649', 'Q9NPC2']","Doxapram is an analeptic agent (a stimulant of the central nervous system). The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted.",CCN1CC(CCN2CCOCC2)C(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1,Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. It is thought to stimulate the carotid body by inhibiting certain potassium channels.TargetActionsOrganismAPotassium channel subfamily K member inhibitorHumansAPotassium channel subfamily K member inhibitorHumans,['Post-operative respiratory stimulation therapy'],"['Agents that produce hypertension', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Increased Medullary Respiratory Drive', 'Pyrrolidines', 'Pyrrolidinones', 'Respiratory System Agents']" +DB01216,Finasteride,Finasterideis an antiandrogenic compound that is used for the treatment of symptomatic benign prostatic hyperplasia (BPH) and male pattern hair loss in adult males by inhibiting Type II 5-alpha reductase.,"['P31213', 'P18405', 'P51857']","Finasteride is an antiandrogenic compound that works by suppressing the production of serum and intraprostatic dihydrotestosterone (DHT) in men via inhibiting the enzyme responsible for the biosynthesis of DHT. The maximum effect of a rapid reduction in serum DHT concentration is expected to be observed 8 hours following administration of the first dose.13In a single man receiving a single oral dose of 5 mg finasteride for up to 4 years, there was a reduction in the serum DHT concentrations by approximately 70% and the median circulating level of testosterone increased by approximately 10-20% within the physiologic range.13In a double-blind, placebo-controlled study, finasteride reduced intraprostatic DHT level by 91.4% but finasteride is not expected to decrease the DHT levels to castrate levels since circulating testosterone is also converted to DHT by the type 1 isoenzyme expressed in other tissues.1It is expected that DHT levels return to normal within 14 days upon discontinuation of the drug.12In a study of male patients with benign prostatic hyperplasia prior to prostatectomy, the treatment with finasteride resulted in an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery compared to placebo.13While finasteride reduces the size of the prostate gland by 20%, this may not correlate well with improvement in symptoms.8The effects of finasteride are reported to be more pronounced in male patients with enlarged prostates (>25 mL) who are at the greatest risk of disease progression.1In phase III clinical studies, oral administration of finasteride in male patients with male pattern hair loss promoted hair growth and prevented further hair loss by 66% and 83% of the subjects, respectively, which lasted during two years' treatment.6The incidences of these effects in treatment groups were significantly higher than that of the group receiving a placebo.6Following finasteride administration, the levels of DHT in the scalp skin was shown to be reduced by more than 60%, indicating that the DHT found in scalp is derived from both local DHT production and circulating DHT.5The effect of finasteride on scalp DHT is likely seen because of its effect on both local follicular DHT levels as well as serum DHT levels.5. There is evidence from early clinical observations and controlled studies that finasteride may reduce bleeding of prostatic origin.3",[H][C@@]12CC[C@H](C(=O)NC(C)(C)C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])NC(=O)C=C[C@]12C,"Finasteride acts as a competitive and specific inhibitor of Type II α-reductase, a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, α-dihydrotestosterone (DHT).DHT is considered to be the primary androgen playing a role in the development and enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland.DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosteroneand by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation.Responsible for the production of DHT together with type I α-reductase, the type II α-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver.Although finasteride is -fold more selective for type II α-reductase than for the type I isoenzyme,chronic treatment with this drug may have some effect on type I α-reductase, which is predominantly expressed in sebaceous glands of most regions of skin, including the scalp, and liver. It is proposed that the type I α-reductase and type II α-reductase is responsible for the production of one-third and two-thirds of circulating DHT, respectively.The mechanism of action of Finasteride is based on its preferential inhibition of Type II α-reductase through the formation of a stable complex with the enzymein vitroandin vivo.Finasteride works selectively, where it preferentially displays a -fold selectivity for the human Type II α-reductase over type I enzyme.Inhibition of Type II α-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations, minimal to moderate increase in serum testosterone concentrations, and substantial increases in prostatic testosterone concentrations. As DHT appears to be the principal androgen responsible for stimulation of prostatic growth, a decrease in DHT concentrations will result in a decrease in prostatic volume (approximately -% after - months of continued therapy). It is suggested that increased levels of DHT can lead to potentiated transcription of prostaglandin D, which promotes the proliferation of prostate cancer cells.In men with androgenic alopecia, the mechanism of action has not been fully determined, but finasteride has shown to decrease scalp DHT concentration to the levels found in the hairy scalp, reduce serum DHT, increase hair regrowth, and slow hair loss. Another study suggests that finasteride may work to reduce bleeding of prostatic origin by inhibiting vascular endothelial growth factor (VEGF) in the prostate, leading to atrophy and programmed cell death.This may bestow the drug therapeutic benefits in patients idiopathic prostatic bleeding, bleeding during anticoagulation, or bleeding after instrumentation.TargetActionsOrganismA-oxo--alpha-steroid -dehydrogenase inhibitorHumansU-oxo--alpha-steroid -dehydrogenase inhibitorHumansU-oxo--beta-steroid -dehydrogenaseinhibitorHumans",[],"['5-alpha Reductase Inhibitors', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Androstanes', 'Androstenes', 'Azasteroids', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs Used in Benign Prostatic Hypertrophy', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Misc. Skin and Mucous Membrane Agents', 'Steroid Synthesis Inhibitors', 'Steroids', 'Urological Agents', 'Urologicals']" +DB00444,Teniposide,Teniposideis a cytotoxic drug used as an adjunct for chemotherapy induction in the treatment of refractory childhood acute lymphoblastic leukemia.,['P11388'],"Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G 2 phase of the cell cycle. Teniposide prevents cell mitosis by causing single and double stranded DNA breaks as well as cross linking between protein and DNA.",[H][C@]12COC(=O)[C@]1([H])[C@H](C1=CC(OC)=C(O)C(OC)=C1)C1=C(C=C3OCOC3=C1)[C@H]2O[C@]1([H])O[C@]2([H])CO[C@H](O[C@@]2([H])[C@H](O)[C@H]1O)C1=CC=CS1,"The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. Teniposide binds to and inhibits DNA topoisomerase II. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.TargetActionsOrganismADNA topoisomerase -alphainhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Carbohydrates', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Glucosides', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Neurotoxic agents', 'Podophyllotoxin Derivatives', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01204,Mitoxantrone,"Mitoxantroneis a chemotherapeutic agent used for the treatment of secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis.",['P11388'],"Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2.",OCCNCCNC1=CC=C(NCCNCCO)C2=C1C(=O)C1=C(C(O)=CC=C1O)C2=O,"Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.TargetActionsOrganismADNAintercalationHumansADNA topoisomerase -alphainhibitorHumans",['Autologous hematopoietic stem cell transplant'],"['Analgesics', 'Anthracenes', 'Anthracyclines and Related Substances', 'Anthraquinones', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cardiotoxic antineoplastic agents', 'Central Nervous System Agents', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers (weak)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Cytotoxic Antibiotics and Related Substances', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Peripheral Nervous System Agents', 'Quinones', 'Sensory System Agents', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01196,Estramustine,Estramustineis an antineoplastic agent used for the management of metastatic and/or progressive prostate cancer in palliative setting.,"['Q92731', 'P03372', 'P11137', 'P78559']","Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components.. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage.",[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(OC(=O)N(CCCl)CCCl)C=C3CC[C@@]21[H],"Estramustine is a derivative of estradiol with a nitrogen mustard moiety. This gives it alkylating properties. In vivo, the nitrogen mustard component is active and can alklyate DNA and other cellular components (such as tubulin components) of rapidly dividing cells. This causes DNA strandbreaks or misscoding events. This leads to apoptosis and cell death. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors.TargetActionsOrganismAEstrogen receptor betaother/unknownHumansAEstrogen receptor alphaagonistHumansAMicrotubule-associated protein antagonistHumansAMicrotubule-associated protein AantagonistHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Fused-Ring Compounds', 'Hydrocarbons, Halogenated', 'Immunosuppressive Agents', 'Mustard Compounds', 'Nitrogen Mustard Compounds', 'Noxae', 'P-glycoprotein inhibitors', 'Steroids', 'Toxic Actions']" +DB01177,Idarubicin,Idarubicinis an anthracycline antineoplastic agent used to treat acute myeloid leukemia (AML) in adults.,['P11388'],"Idarubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Idarubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Idarubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.",C[C@@H]1O[C@H](C[C@H](N)[C@@H]1O)O[C@H]1C[C@@](O)(CC2=C1C(O)=C1C(=O)C3=CC=CC=C3C(=O)C1=C2O)C(C)=O,"Idarubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Idarubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.TargetActionsOrganismADNAintercalationHumansADNA topoisomerase -alphainhibitorHumans",[],"['Anthracycline Topoisomerase Inhibitor', 'Anthracyclines', 'Anthracyclines and Related Substances', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Cytotoxic Antibiotics and Related Substances', 'Enzyme Inhibitors', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Naphthacenes', 'Narrow Therapeutic Index Drugs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01143,Amifostine,Amifostineis a cytoprotective adjuvant used for reduction in the cumulative renal toxicity in patients with ovarian cancer and moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer.,['P10696'],"Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumour cells.",NCCCNCCSP(O)(O)=O,"The thiol metabolite is responsible for most of the cytoprotective and radioprotective properties of amifostine. It is readily taken up by cells where it binds to and detoxifies reactive metabolites of platinum and alkylating agents as well as scavenges free radicals. Other possible effects include inhibition of apoptosis, alteration of gene expression and modification of enzyme activity.TargetActionsOrganismAAlkaline phosphatase, germ cell typeinducerHumans",[],"['Compounds used in a research, industrial, or household setting', 'Cytoprotective Agent', 'Detoxifying Agents for Antineoplastic Treatment', 'Free Radical Scavenging Activity', 'Hypotensive Agents', 'Organophosphates', 'Organophosphorus Compounds', 'Organothiophosphates', 'Organothiophosphorus Compounds', 'Protective Agents', 'Radiation-Protective Agents', 'Sulfur Compounds']" +DB00445,Epirubicin,Epirubicinis an anthracycline topoisomerase II inhibitor used as an adjuvant to treating axillary node metastases in patients who have undergone surgical resection of primary breast cancer.,['P11388'],"Epirubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Epirubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Epirubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.",COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O,"Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.TargetActionsOrganismUDNAintercalationHumansUDNA topoisomerase -alphainhibitorHumans",[],"['Anthracycline Topoisomerase Inhibitor', 'Anthracyclines', 'Anthracyclines and Related Substances', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cardiotoxic antineoplastic agents', 'Cytotoxic Antibiotics and Related Substances', 'Enzyme Inhibitors', 'Glycosides', 'Hepatotoxic Agents', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Naphthacenes', 'Narrow Therapeutic Index Drugs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors', 'UGT2B7 substrates', 'UGT2B7 Substrates with a Narrow Therapeutic Index']" +DB00897,Triazolam,Triazolamis a benzodiazepine used for short term treatment of insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","A short-acting benzodiazepine used as a hypnotic agent in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. Triazolam has a shorter half-life than chlordiazepoxide, flurazepam, and prazepam and does not generate active metabolites.",CC1=NN=C2CN=C(C3=CC=CC=C3Cl)C3=C(C=CC(Cl)=C3)N12,"Benzodiazepines bind nonspecifically to bezodiazepine receptors BNZ, which mediates sleep, and BNZ, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",['Sedation'],"['Adjuvants, Anesthesia', 'Agents Causing Muscle Toxicity', 'Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'Triazolobenzodiazepines']" +DB01043,Memantine,Memantineis an NMDA receptor antagonist used to treat moderate to severe dementia in Alzheimer's.,"['Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'P46098', 'Q693P7', 'P14416', 'Q05586', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P23415', 'P23416', 'O75311', 'Q5JXX5', 'P48167']","General effectsThis drug inhibits calcium influx into cells that is normally caused by chronic NMDA receptor activation by glutamate3. This leads to the improvement of Alzheimer's dementia symptoms, demonstrated by increased cognition and other beneficial central nervous system effects3.Effects on neuroplasticityLike other NMDA receptor antagonists, memantine at high doses can reduce neuronal synaptic plasticity that is involved in learning and memory processes. At lower concentrations, which are normally used in the clinical setting, memantine can enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons caused by excitatory neurotransmitters2.Effect on various receptorsMemantine has demonstrated minimal activity for GABA, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors, as well as voltage-dependent Ca2+, Na+ or K+ channels. This drug has shown antagonist activity at the 5HT3 receptors. Laboratory studies suggest that memantine does not affect the reversible inhibition of the acetylcholinesterase normally caused by donepezil, galantamine, or tacrineLabel.",CC12CC3CC(C)(C1)CC(N)(C3)C2,"Continuous activation of the N-methyl-D-aspartate (NMDA) receptors in the central nervous system caused byglutamateis thought to cause some of the Alzheimer's disease symptoms. This overactivation is thought to contribute to neurotoxicity due to the excitatory properties of glutamate. The pharmacological effect of memantine likely occurs via the drug's behavior as an uncompetitive (open-channel) NMDA receptor antagonist, preventing glutamate action on this receptor. Memantine has a preference for the NMDA receptor-operated cation channels. Despite these antagonist effects, memantine has not been proven to prevent or retard the neurodegeneration seen in patients diagnosed with Alzheimer’s diseaseLabel.TargetActionsOrganismAGlutamate (NMDA) receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansUAlpha- nicotinic cholinergic receptor subunitantagonistHumansUDopamine D receptorantagonistagonistHumansUGlutamate receptor ionotropic, NMDA binderHumansUGABA(A) ReceptorbinderHumansUGlycine receptorsinhibitorHumans",[],"['Anti-Dementia Drugs', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Bridged-Ring Compounds', 'Central Nervous System Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (weak)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dopamine Agents', 'Drugs that are Mainly Renally Excreted', 'Excitatory Amino Acid Antagonists', 'Miscellaneous Central Nervous System Agents', 'N-methyl-D-aspartate Receptor Antagonist', 'Nervous System', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'OCT2 Substrates', 'Psychoanaleptics']" +DB00494,Entacapone,Entacaponeis a selective reversible catechol-O-methyltransferase inhibitor for the treatment of Parkinson's disease.,['P21964'],"Entacapone is structurally and pharmacologically related to tolcapone, but unlike tolcapone, is not associated with hepatotoxicity. Entacapone is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Entacapone selectively and reversiblly inhibits catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa, catalyzing the it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.",CCN(CC)C(=O)C(=C\C1=CC(=C(O)C(O)=C1)[N+]([O-])=O)\C#N,"The mechanism of action of entacapone is believed to be through its ability to inhibit COMT in peripheral tissues, altering the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to a greater reduction in the manifestations of parkinsonian syndrome.TargetActionsOrganismACatechol O-methyltransferaseinhibitorHumans",[],"['Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Benzene Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'COMT Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dopamine Agents', 'Enzyme Inhibitors', 'Nervous System', 'Phenols', 'UGT1A9 Substrates']" +DB00850,Perphenazine,Perphenazineis a phenothiazine used to treat schizophrenia as well as nausea and vomiting.,"['P14416', 'P21728', 'P0DP23']","Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol.",OCCN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1,Binds to the dopamine D and dopamine D receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansUCalmodulininhibitorHumans,[],"['Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Phenothiazines', 'Phenothiazines With Piperazine Structure', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB00206,Reserpine,"An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.","['Q05940', 'P54219', 'O15392']","Reserpine is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance.",[H][C@]12C[C@@H](OC(=O)C3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=C3C=CC(OC)=C1)C2,Reserpine's mechanism of action is through inhibition of the ATP/Mg+pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase (MAO) causing a reduction in catecholamines.TargetActionsOrganismASynaptic vesicular amine transporterinhibitorHumansUChromaffin granule amine transporterinhibitorHumansUBaculoviral IAP repeat-containing protein Not AvailableHumans,[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Alkaloids', 'Antiadrenergic Agents, Centrally Acting', 'Antidepressive Agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Antipsychotic Agents', 'BSEP/ABCB11 Inhibitors', 'Cardiovascular Agents', 'Catecholamine-depleting Sympatholytic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Decreased Sympathetic Activity', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Acidifying Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Membrane Transport Modulators', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT2 Substrates', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Psychotropic Drugs', 'Secologanin Tryptamine Alkaloids', 'Tranquilizing Agents']" +DB00176,Fluvoxamine,Fluvoxamineis a selective serotonin-reuptake inhibitor used to treat obsessive-compulsive disorder.,"['P31645', 'Q12809']","Fluvoxamine, an aralkylketone-derivative agentLabel, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs1. It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety1. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotoninLabel,1,2.In vitrostudies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake2. Moreover, apart from binding to σ1 receptors2, fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs1. Furthermore, some studies have demonstrated that the chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors (as has been observed with other drugs effective in the treatment of major depressive disorder), while others suggest the opposite3.",COCCCC\C(=N/OCCN)C1=CC=C(C=C1)C(F)(F)F,"The exact mechanism of action of fluvoxamine has not been fully determined, but appears to be linked to its inhibition of CNS neuronal uptake of serotoninLabel,,. Fluvoxamine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on HTAautoreceptorsLabel,,. Studies have also demonstrated that fluvoxamine has virtually no affinity for α- or α-adrenergic, β-adrenergic, muscarinic, dopamine D, histamine H, GABA-benzodiazepine, opiate, -HT, or -HTreceptors, despite having an affinity for binding to σ receptors.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansUPotassium voltage-gated channel subfamily H member Not AvailableHumans",[],"['Amines', 'Anti-Anxiety Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'BSEP/ABCB11 Substrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hydroxylamines', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Oximes', 'P-glycoprotein inhibitors', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Tranquilizing Agents']" +DB12129,Tideglusib,Tideglusib is under the investigation for the development of treatments for Alzheimer's disease and for progressive supranuclear palsy. It is reported to be a potent anti-inflammatory and neuroprotective that is a non-ATP competitive inhibitor of glycogen synthase kinase 3 (GSK-3).1Tideglusib is being developed by the Spanish pharmaceutic company Zeltia group and its current status is withdrawn for the treatment of Alzheimer's disease as of 2012.,['P49841'],"It is reported that tideglusib administration inhibits the activation of astrocytes and microglial cells, thus it presented a neuroprotective effect. It is known as well that the inactivation of GSK-3 protects against excitotoxicity.1In pre-clinical trials, there have been reports of decrease Tau hyperphosphorylation, lower brain amyloid plaque load, learning and memory enhancement, prevention of neuronal loss and significant increases of the insulin growth factor 1 which is a potent neurotrophic peptide with therapeutic value.The reports in clinical trials have shown a trend in cognition increase of Alzheimer patients treated for 24 weeks.3,4",O=C1SN(C(=O)N1CC1=CC=CC=C1)C1=C2C=CC=CC2=CC=C1,"GSK- is a proline/serine protein kinase that is ubiquitously expressed and involved in many cellular signaling pathways. From all its diverse functions, it plays a key role in Alzheimer's disease. This role is related to its link with β-amyloid and tau pathology. It has been suggested that aberrant Wnt or insulin signaling results in increased GSK- function. This kinase acts on γ-secretase producing the hyperphosphorylation of tau, the formation of neurofibrillary tangles and senile plaques.Tideglusib inhibits GSK- irreversibly by presenting a non-competitive inhibition pattern with respect to ATP. The binding of tideglusib seems to directly relate to the motif containing Cys.TargetActionsOrganismAGlycogen synthase kinase- betaantagonistHumans",[],"['Glycogen Synthase Kinase 3, antagonists & inhibitors', 'Sulfur Compounds', 'Thiazoles']" +DB00014,Goserelin,Goserelinis a synthetic analog of luteinizing hormone-releasing hormone used to treat breast cancer and prostate cancer by reducing secretion of gonadotropins from the pituitary.,"['P22888', 'P30968']","The pharmacokinetics of goserelin have been determined in both male and female healthy volunteers and patients. In these studies, goserelin was administered as a single 250µg (aqueous solution) dose and as a single or multiple 3.6 mg depot dose by subcutaneous route.",CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O,Goserelin is a synthetic decapeptide analogue of LHRH. Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. The result is sustained suppression of LH and serum testosterone levels.TargetActionsOrganismALutropin-choriogonadotropic hormone receptoragonistHumansAGonadotropin-releasing hormone receptoragonistHumans,['Palliative Treatment'],"['Adrenal Cortex Hormones', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Gonadotropin Releasing Hormone Receptor Agonist', 'Gonadotropin Releasing Hormone Receptor Agonists', 'Gonadotropin-releasing hormone agonist', 'Gonadotropins and Antigonadotropins', 'Hormones', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Hypothalamic Hormones', 'Miscellaneous Therapeutic Agents', 'Moderate Risk QTc-Prolonging Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary Hormone-Releasing Hormones', 'QTc Prolonging Agents']" +DB00934,Maprotiline,"Maprotilineis a tetracyclic antidepressant used to treat depressive illness, major depressive disorder, bipolar disorder, and anxiety associated with depression.","['P23975', 'P35367', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P35348', 'P35368', 'P25100', 'P28223', 'P28335', 'P34969', 'P14416', 'P08913', 'P18089', 'P18825']","Maprotiline is a tetracyclic antidepressant. Although its main therapeutic use is in the treatment of depression, it has also been shown to exert a sedative effect on the anxiety component that often accompanies depression. In one sleep study, it was shown that maprotiline increases the duration of the REM sleep phase in depressed patients, compared to imipramine which reduced the REM sleep phase. Maprotiline is a strong inhibitor of noradrenaline reuptake in the brain and peripheral tissues, however it is worthy to note that it is a weak inhibitor of serotonergic uptake. In addition, it displays strong antihistaminic action (which may explain its sedative effects) as well as weak anticholinergic action. Maprotiline also has lower alpha adrenergic blocking activity than amitriptyline.",CNCCCC12CCC(C3=CC=CC=C13)C1=CC=CC=C21,"Maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold. Maprotiline acts as an antagonist at central presynaptic α-adrenergic inhibitory autoreceptors and hetero-receptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Maprotiline is also a moderate peripheral αadrenergic antagonist, which may explain the occasional orthostatic hypotension reported in association with its use. Maprotiline also inhibits the amine transporter, delaying the reuptake of noradrenaline and norepinephrine. Lastly, maprotiline is a strong inhibitor of the histamine Hreceptor, which explains its sedative actions.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansNHistamine H receptorantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNAlpha- adrenergic receptorsantagonistHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor CbinderHumansU-hydroxytryptamine receptor antagonistHumansUDopamine D receptorbinderHumansUAlpha- adrenergic receptorsantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Anthracenes', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Antidepressive Agents, Tetracyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB00981,Physostigmine,Physostigmineis a cholinesterase inhibitor used to treat glaucoma and anticholinergic toxicity.,"['P22303', 'P43681', 'P17787']","Physostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. Physostigmine is used to treat glaucoma. Because it crosses the blood-brain barrier, it is also used to treat the central nervous system effects of atropine overdose and other anticholinergic drug overdoses. Physostigmine can reverse both central and peripheral anticholinergia.",[H][C@]12N(C)CC[C@@]1(C)C1=C(C=CC(OC(=O)NC)=C1)N2C,"Physostigmine inhibits acetylcholinesterase, the enzyme responsible for the breakdown of used acetylcholine. By interfering with the metabolism of acetylcholine, physostigmine indirectly stimulates both nicotinic and muscarinic receptors due to the consequential increase in available acetylcholine at the synapse.TargetActionsOrganismAAcetylcholinesteraseinhibitorHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumans",[],"['Acids, Acyclic', 'Alkaloids', 'Antidotes', 'Antiglaucoma Preparations and Miotics', 'Autonomic Agents', 'Carbamates', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Miotics', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Phenylcarbamates', 'Sensory Organs']" +DB11081,Aluminum chloride,"Aluminum chloride is a chemical compound with the chemical formula AlCl3. When contaminated with iron chloride, it often displays a yellow color compared to the white pure compound. It is used in various chemical applications as a Lewis base, with anhydrous aluminium trichloride being the most commonly used Lewis acid. It may also be found in over-the-counter as an antiperspirant or prescription products as an antihemorrhagic agent. In antiperspirant products, FDA approves the use of aluminum chloride as an active ingredient up to 15%, calculated on the hexahydrate form, in an aqueous solution nonaerosol dosage form4.",['P00367'],Aluminum chloride is a hemostatic and antiperspirant agent.,Cl[Al](Cl)Cl,"Aluminum chloride is commonly used topical antiperspirant. It is proposed that aluminum chloride works by causing an obstruction of the distal sweat gland ducts, where the metal ions precipitate with mucopolysaccharides, damaging epithelial cells along the lumen of the duct and forming a plug that blocks sweat output. Aluminum chloride is also an astringent that promotes hemostasis; it precipitates proteins on the superficial layer of mucosa and make it mechanically stronger. It creates superficial and local coagulation in minor hemorrhages.TargetActionsOrganismUGlutamate dehydrogenase , mitochondrialinactivatorHumans",[],"['Aluminium Compounds', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Antiperspirants', 'Astringents and Deodorants', 'Chlorides', 'Chlorine Compounds', 'Compounds used in a research, industrial, or household setting', 'Cosmetics', 'Dental Agents', 'Dermatologicals', 'Metal cations', 'Metal divalent cations']" +DB00674,Galantamine,Galantamineis a cholinesterase inhibitor used to manage mild to moderate dementia associated with Alzheimer's Disease.,"['P22303', 'P36544', 'A9X444', 'P06276']","Galantamine is a competitive and reversible inhibitor of acetylcholinesterase that works to increase acetylcholine levels.10Galantamine acts both centrally and peripherally to inhibit both muscle and brain acetylcholinesterase, thereby increasing cholinergic tone.5Galantamine is also a positive allosteric modulator of neuronal nicotinic acetylcholine receptors.3,5As dementia is a progressive neurodegenerative disease, galatamine has a negligible effect in altering the course of the underlying process of dementia10and may exert its therapeutic effectiveness for a short period of time.8However, galantamine promoted improvements in cognition, global function, activities of daily living, and behavioural symptoms in clinical studies of Alzheimer’s disease.1,7Galantamine exhibited therapeutic efficacy in studies of vascular dementia and Alzheimer’s disease with cerebrovascular disease.7In one study, galantamine reversed scopolamine-induced acute anticholinergic syndrome that was characterized by drowsiness, disorientation, and delirium.5",[H][C@]12C[C@@H](O)C=C[C@]11CCN(C)CC3=C1C(O2)=C(OC)C=C3,"Alzheimer’s disease is characterized by progressive, irreversible degeneration of acetylcholine-producing neurons, cognitive impairment, and the accumulation of neurofibrillary tangles and amyloid plaques.,The cholinergic system plays a critical role in memory, alongside other important neural functions such as attention, learning, stress response, wakefulness and sleep, and sensory information. Studies show that acetylcholine (ACh) is involved in the modulation of acquisition, encoding, consolidation, reconsolidation, extinction, and retrieval of memory. The gradual loss of cholinergic neurons in Alzheimer’s disease (AD) may, therefore, contribute to the memory loss exhibited by AD patients.Acetylcholinesterase is secreted by cholinergic neurons to rapidly hydrolyze ACh at the synaptic cleft to release acetate and choline. Choline is later recycled back into the presynaptic cholinergic neuron via reuptake by the high-affinity choline transporter. There is some evidence demonstrating the potential involvement of the acetylcholinesterase enzyme in the formation of amyloid fibrils.Galantamine competitively and reversibly inhibits the anticholinesterase enzyme in the CNS (namely in the frontal cortex and hippocampal regions)by binding to the choline-binding site and acyl-binding pocket of the enzyme active site.By blocking the breakdown of ACh, galantamine enhances ACh levels in the synaptic cleft.Nicotinic acetylcholine receptors (nAChR) in the CNS are mostly expressed at the presynaptic neuronal membrane to control the release of multiple neurotransmitters, such as ACh, glutamate, GABA, dopamine, serotonin, norepinephrine.,Agonists of nAChRs improve performance in cognitive tasks, while antagonists of nAChR impair cognitive processes.Some studies show a decrease in the expression and activity of nAChRs in patients with AD, which may explain the reduction in central cholinergic neurotransmission in these patients.Galantamine binds to nAChRs at the allosteric site,,leading to a conformational change of the receptor, increased ACh release, and increased activity of neighbouring glutaminergic and serotoninergic neurons.The modulation of nAChRs facilitates both excitatory and inhibitory cholinergic transmissions in brain tissues and increases receptor sensitivity. The modulated release of other neurotransmitters by galantamine may also contribute to the upregulation of nAChRs and amelioration of behavioural symptoms in AD.TargetActionsOrganismAAcetylcholinesteraseinhibitorHumansANeuronal acetylcholine receptor subunit alpha-allosteric modulatorHumansUMuscle nicotinic acetylcholine receptorallosteric modulatorHumansUCholinesteraseinhibitorHumans",[],"['Alkaloids', 'Amaryllidaceae Alkaloids', 'Anti-Dementia Drugs', 'Autonomic Agents', 'Benzazepines', 'Bradycardia-Causing Agents', 'Central Nervous System Agents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Nootropic Agents', 'P-glycoprotein inhibitors', 'Parasympathomemetic (Cholinergic) Agents', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'QTc Prolonging Agents']" +DB01618,Molindone,Molindoneis an antipsychotic used to treat schizophrenia.,"['P14416', 'P08908', 'P28223', 'P11229']","Molindone is a dihydroindolone compound which is not structurally related to the phenothiazines, the butyrophenones, or the thioxanthenes. Molindone has a pharmacological profile in laboratory animals which predominantly resembles that of major tranquilizers causing reduction of spontaneous locomotion and aggressiveness, suppression of a conditioned response and antagonism of the bizarre stereotyped behavior and hyperactivity induced by amphetamines. In addition, molindone antagonizes the depression caused by the tranquilizing agent tetrabenazine.",CCC1=C(C)NC2=C1C(=O)C(CN1CCOCC1)CC2,"The exact mechanism has not been established, however, based on electroencephalogram (EEG) studies, molindone is thought to act by occupying (antagonizing) dopamine (D) receptor sites in the reticular limbic systems in the brain, thus decreasing dopamine activity. Decreased dopamine activity results in decreased physiological effects normally induced by excessive dopamine stimulation, such as those typically seen in manifestations of psychotic disorders.TargetActionsOrganismADopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor AantagonistHumansUMuscarinic acetylcholine receptor Mother/unknownHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Indole Derivatives', 'Indoles', 'Nervous System', 'Neurotoxic agents', 'Psycholeptics', 'Psychotropic Drugs', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB04864,Huperzine A,"Huperzine A, is a naturally occurring sesquiterpene alkaloid found in the extracts of the firmossHuperzia serrata. The botanical has been used in China for centuries for the treatment of swelling, fever and blood disorders. Recently in clinical trials in China, it has demonstrated neuroprotective effects. It is currently being investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer’s disease.",['P22303'],"Huperzine A is an alkaloid derived fromHuperzia serrata(which is available as an herbal product in the US). It is under investigation as an acetylcholinesterase inhibitor. Clinical trials in China have shown that huperzine A is comparably effective to the drugs currently on the market, and may even be somewhat safer in terms of side effects.",[H][C@@]12CC3=C(C=CC(=O)N3)[C@@](N)(CC(C)=C1)\C2=C\C,Huperzine A has been found to be an inhibitor of the enzyme acetylcholinesterase. This is the same mechanism of action of pharmaceutical drugs such asgalantamineanddonepezilused to treat Alzheimer's disease.TargetActionsOrganismUAcetylcholinesteraseinhibitorHumans,[],"['Central Nervous System Agents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Compounds used in a research, industrial, or household setting', 'Enzyme Inhibitors', 'Neuroprotective Agents', 'Neurotransmitter Agents', 'Protective Agents', 'Terpenes']" +DB00989,Rivastigmine,Rivastigmineis a cholinesterase inhibitor used to treat mild to moderate dementia in Alzheimer's and Parkinson's.,"['P22303', 'P06276']","Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. While the precise mechanism of rivastigmine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this proposed mechanism is correct, rivastigmine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact.",CCN(C)C(=O)OC1=CC=CC(=C1)[C@H](C)N(C)C,"Rivastigmine is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine. The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hydrolysis of acetycholine, and thus leading to an increased concentration of acetylcholine at cholinergic synapses. The anticholinesterase activity of rivastigmine is relatively specific for brain acetylcholinesterase and butyrylcholinesterase compared with those in peripheral tissues.TargetActionsOrganismAAcetylcholinesteraseinhibitorHumansACholinesteraseinhibitorHumans",[],"['Acids, Acyclic', 'Anti-Dementia Drugs', 'Bradycardia-Causing Agents', 'Carbamates', 'Central Nervous System Agents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Compounds used in a research, industrial, or household setting', 'Enzyme Inhibitors', 'Nervous System', 'Neuroprotective Agents', 'Neurotransmitter Agents', 'Parasympathomemetic (Cholinergic) Agents', 'Phenylcarbamates', 'Protective Agents', 'Psychoanaleptics']" +DB00382,Tacrine,Tacrineis an anticholinesterase drug used for the management of Alzheimer's disease symptoms.,"['P06276', 'P22303', 'P23141']","Tacrine is a parasympathomimetic- a reversible cholinesterase inhibitor that is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine at cholinergic synapses through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, tacrine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that tacrine alters the course of the underlying dementing process.",NC1=C2CCCCC2=NC2=CC=CC=C12,"The mechanism of tacrine is not fully known, but it is suggested that the drug is an anticholinesterase agent which reversibly binds with and inactivates cholinesterases. This inhibits the hydrolysis of acetylcholine released from functioning cholinergic neurons, thus leading to an accumulation of acetylcholine at cholinergic synapses. The result is a prolonged effect of acetylcholine.TargetActionsOrganismACholinesteraseinhibitorHumansAAcetylcholinesteraseinhibitorHumansULiver carboxylesterase Not AvailableHumans",[],"['Acridines', 'Agents Causing Muscle Toxicity', 'Aminoacridines', 'Anti-Dementia Drugs', 'Autonomic Agents', 'Central Nervous System Agents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Nootropic Agents', 'P-glycoprotein substrates', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Psychoanaleptics']" +DB00323,Tolcapone,Tolcaponeis a catechol-O-methyltransferase (COMT) inhibitor used as adjunct therapy in the symptomatic management of idiopathic Parkinson's disease.,['P21964'],"Tolcapone is a potent, selective, and reversible inhibitor of catechol-O-methyltransferase (COMT). In humans, COMT is distributed throughout various organs. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa.",CC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)[N+]([O-])=O,"The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa, resulting in an increase in plasma levodopa concentrations. The inhibition of COMT also causes a reduction in circulating -OMD as a result of decreased peripheral metabolism of levodopa. This may lead to an increase distribution of levodopa into the CNS through the reduction of its competitive substrate, -OMD, for transport mechanisms. Sustained levodopa concentrations presumably result in more consistent dopaminergic stimulation, resulting in greater reduction in the manifestations of parkinsonian syndrome.TargetActionsOrganismACatechol O-methyltransferaseinhibitorHumans",[],"['Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Benzene Derivatives', 'Benzophenones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'COMT Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dopamine Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Ketones', 'Nervous System', 'Nitro Compounds', 'Nitrophenols', 'Phenols']" +DB00189,Ethchlorvynol,Ethchlorvynolis a sedative hypnotic agent used for the short-term management of insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","Ethchlorvynol is a sedative drug and schedule IV (USA) controlled substance. It produces cerebral depression, however the exact mechanism of action is not known.",CCC(O)(\C=C\Cl)C#C,"Although the exact mechanism of action is unknown, ethchlorvynol appears to depress the central nervous system in a manner similar to that of barbiturates. Barbiturates bind at a distinct binding sites associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumans",[],"['Alcohols', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Chlorohydrins', 'Hypnotics and Sedatives', 'Nervous System', 'Psycholeptics']" +DB00330,Ethambutol,Ethambutolis an antituberculosis agent used in the prophylaxis and treatment of tuberculosis (TB).,"['P9WNL5', 'P9WNL7', 'P9WNL9']","Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis.12It has a long duration of action as it is administered daily, and a moderate therapeutic window.12Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.12",CC[C@@H](CO)NCCN[C@@H](CC)CO,"Ethambutol diffuses intoMycobacteriumcells.Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division.,,,Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate.,Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells.Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells.TargetActionsOrganismAProbable arabinosyltransferase CinhibitorMycobacterium tuberculosisAProbable arabinosyltransferase BinhibitorMycobacterium tuberculosisAProbable arabinosyltransferase AinhibitorMycobacterium tuberculosis",[],"['Amines', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Diamines', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Ethylenediamines', 'Polyamines']" +DB00246,Ziprasidone,"Ziprasidoneis an atypical antipsychotic used to manage schizophrenia, bipolar mania, and agitation in patients with schizophrenia.","['P14416', 'P28223', 'P08908', 'P28221', 'P28335', 'P21728', 'P21918', 'P35462', 'P21917', 'P28222', 'P28566', 'P50406', 'P34969', 'P35367', 'P35348', 'P35368', 'P08913', 'P18089', 'P18825', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P46098', 'O95264', 'Q8WXA8', 'Q70Z44', 'A5X5Y0', 'P47898']","Ziprasidone is classified as a ""second generation"" or ""atypical"" antipsychotic and is a dopamine and 5HT2A receptor antagonist with a unique receptor binding profile. As previously mentioned, ziprasidone has a very high 5-HT2A/D2 affinity ratio, binds to multiple serotonin receptors in addition to 5-HT2A, and blocks monoamine transporters which prevents 5HT and NE reuptake. On the other hand, ziprasidone has a low affinity for muscarinic cholinergic M1, histamine H1, and alpha1-adrenergic receptors.4",ClC1=C(CCN2CCN(CC2)C2=NSC3=CC=CC=C23)C=C2CC(=O)NC2=C1,"The effects of ziprasidone are differentiated from other antispychotics based on its preference and affinity for certain receptors. Ziprasidone binds to serotonin-A (-HTA) and dopamine D receptors in a similar fashion to other atypical antipsychotics; however, one key difference is that ziprasidone has a higher -HTA/D receptor affinity ratio when compared to other antipsychotics such as olanzapine, quetiapine, risperidone, and aripiprazole.Ziprasidone offers enhanced modulation of mood, notable negative symptom relief, overall cognitive improvement and reduced motor dysfunction which is linked to it's potent interaction with -HTC, -HTD, and -HTA receptors in brain tissue.Ziprasidone can bind moderately to norepinephrine and serotonin reuptake sites which may contribute to its antidepressant and anxiolytic activity.Patient's taking ziprasidone will likely experience a lower incidence of orthostatic hypotension, cognitive disturbance, sedation, weight gain, and disruption in prolactin levels since ziprasidone has a lower affinity for histamine H, muscarinic M, and alpha-adrenoceptors.TargetActionsOrganismADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor AagonistHumansA-hydroxytryptamine receptor DantagonistHumansA-hydroxytryptamine receptor CantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor EantagonistHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor antagonistHumansUHistamine H receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansU-hydroxytryptamine receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Highest Risk QTc-Prolonging Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Indole Derivatives', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1D Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB06288,Amisulpride,"Amisulprideis a dopamine D2 receptor antagonist used in the treatment of acute and chronic schizophrenia, and in the prevention and treatment of postoperative nausea and vomiting in adults.","['P34969', 'P28223', 'P14416', 'P35462', 'P35372', 'P41143', 'P41145']","Amisulpride is a selective dopamine D2 and D3 receptor antagonist with no affinity towards other dopamine receptor subtypes. Amisulpride is an atypical antipsychotic agent that works as an antagonist at dopamine receptors in the limbic system. Since it works preferentially in the limbic system, amisulpride is less likely to be associated with extrapyramidal adverse effects than other atypical antipsychotic agents. Amisulpride has no affinity for serotonin, alpha-adrenergic, H1-histamine, cholinergic, and sigma receptors. In clinical trials, amisulpride improved reduced secondary negative symptoms, affective symptoms, and psychomotor retardation in patients with acute exacerbation of schizophrenia. Notably, amisulpride has a differential target binding profile at different doses: at low doses, amisulpride selectively binds to presynaptic dopamine autoreceptors. At high doses, it preferentially binds to post-synaptic dopamine receptors.3This explains how amisulpride reduces negative symptoms at low doses and mediates antipsychotic effects at high doses.11One study alluded that the antinociceptive effects of amisulpride are mediated through opioid receptor acvitation and D2 receptor antagonism.3,5The actions of amisulpride at opioid receptors may explain its pro-convulsant properties.5Amisulpride is also an antiemetic agent that prevents and alleviates postoperative nausea and vomiting. It primarily works by blocking dopamine signalling in the chemoreceptor trigger zone, which is a brain area that relays stimuli to the vomiting center.11In clinical trials comprising Caucasian and Japanese subjects, amisulpride caused dose- and concentration-dependent prolongation of the QT interval; thus, intravenous infusion under a strict dosing regimen and close monitoring of patients with pre-existing cardiovascular conditions are recommended.10Amisulpride increases plasma prolactin levels, leading to an association with benign pituitary tumours such as prolactinoma.11",CCN1CCCC1CNC(=O)C1=CC(=C(N)C=C1OC)S(=O)(=O)CC,"Dopamine is an essential and critical neurotransmitter produced in the substantia nigra and ventral tegmental regions of the brain. Dopaminergic projection function in the nigrostriatal, mesolimbic, and mesocortical systems. Hyperactive dopamine transmission in the mesolimbic areas, or dopamine dysregulation in various major brain regions, is understood as the key driver of positive and negative symptoms of schizophrenia.Many antipsychotic agents act as D receptor antagonists, as with amisulpride.Amisulpride is a selective dopamine D and D receptor antagonist.It has high preferential activity towards dopamine receptors in the limbic system rather than the striatum, leading to a lower risk of extrapyramidal side effects than other atypical antipsychotic agents.,At low doses, amisulpride reduces negative symptoms of schizophrenia by blocking pre-synaptic dopamine D and D receptors, increasing the levels of dopamine in the synaptic cleft and facilitating dopaminergic transmission.At higher doses, amisulpride blocks postsynaptic receptors, inhibiting dopaminergic hyperactivity: this explains the drug improving positive symptoms.Amisulpride also works as an antagonist at -HTAreceptorsand -HTAreceptors,which may be related to its antidepressant effects.The chemoreceptor trigger zone (CTZ), also commonly known as the area postrema (AP), is an important brain region located within the dorsal surface of the medulla oblongata. CTZ is involved in emesis: it contains receptors, such as dopamine receptors, that are activated in response to emetic agents in the blood and relay information to the vomiting center, which is responsible for inducing the vomiting reflex.Amisulpride is an antiemetic agent that works to limit signals that promote nausea and vomiting. Amisulpride binds to D and D receptors in the CTZ, leading to reduced dopaminergic signalling into the vomiting center.TargetActionsOrganismA-hydroxytryptamine receptor antagonistHumansA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansNMu-type opioid receptoragonistHumansNDelta-type opioid receptoragonistHumansNKappa-type opioid receptoragonistHumans",[],"['Acids, Carbocyclic', 'Amides', 'Antidepressive Agents', 'Antidepressive Agents, Second-Generation', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'BCRP/ABCG2 Substrates', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 2 Inhibitors', 'MATE 2 Substrates', 'MATE inhibitors', 'MATE substrates', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'OCT1 substrates', 'Opioid Agonist', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB00391,Sulpiride,Sulpirideis a selective D2 dopamine receptor antagonist indicated to treat chronic and acute schizophrenia.,"['P14416', 'P35462', 'P00918', 'P07451', 'P21917']","Sulpiride is a substituted benzamide derivative and a selective dopamine D2 antagonist indicated to treat acute and chronic schizophrenia.6,7,8,10It has a short duration of action as it is given twice daily, and a wide therapeutic window as patients have survived single doses as high as 16g.10Patients should be counselled regarding increased motor agitation, extrapyramidal reactions, and neuroleptic malignant syndrome.10",CCN1CCCC1CNC(=O)C1=C(OC)C=CC(=C1)S(N)(=O)=O,"Sulpiride is a selective dopamine D and D receptor antagonist.,,In silicostudies show that sulpiride may interact with the Asp- and Phe- amino acid residues of these receptors.It is estimated that D receptors should be -% occupied for optimal treatment and minimal adverse effects.TargetActionsOrganismADopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUDopamine D receptorantagonistHumans",[],"['Acids, Carbocyclic', 'Amides', 'Antidepressive Agents', 'Antidepressive Agents, Second-Generation', 'Antipsychotic Agents', 'BCRP/ABCG2 Substrates', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'OCT1 substrates', 'OCT2 Substrates', 'P-glycoprotein substrates', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Tranquilizing Agents']" +DB00304,Desogestrel,"Desogestrelis a synthetic progestin used in contraception, often in combination with ethinyl estradiol.","['P06401', 'P03372']","The effects of desogestrel are divided on reproductive including modification of luteinizing hormone and follicle stimulating hormone, declines on the onset of menstruation, and increases the viscosity of the vaginal fluid; and on metabolic that includes increase insulin secretion and resistance, increased lipase activity, and increased fat deposition.9The effect of desogestrel on the lipids has been studied extensively and the results are contradictory.Desogestrel main therapeutic effect due to its mechanism of action is known to be related to the inhibition of the ovulation in 97% of the cycles. This effect was proven in clinical trials in non-breastfeeding women from which the Pearl failure rate was reported to be of 0.17 per 100 women-years. This result indicated that desogestrel is more efficient when compared to other progestogen-only pills.6All the therapeutic effect is produced by a transformation of the endometrium followed by an inhibition of the ovulation due to the suppression of other hormones.10Desogestrel has been widely confirmed to be related to an increase in the risk of venous thromboembolism due to the driven increased in blood coagulation factors, leading to a pronounced prothrombotic state.1However, the effects of desogestrel are known to not impact significantly the level of total cholesterol remaining in the range of change of 10% which allows it to be a molecule that presents a favorable lipid profile.4",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC(=C)[C@]1([H])[C@@]3([H])CCCC=C3CC[C@@]21[H],"Desogestrel enters the cell passively and acts by binding selectively to the progesterone receptor and generating low androgenic activity.Its binding produces an effect like a transcription factor and thus, it produces modifications in the mRNA synthesis.The active metabolite of desogestrel,etonogestrel, presents a combination of high progestational activity with minimal intrinsic androgenicity.LabelTargetActionsOrganismAProgesterone receptoragonistHumansAEstrogen receptor alphaagonistHumans",['Contraception'],"['Adrenal Cortex Hormones', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Contraceptives, Oral, Synthetic', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Norpregnanes', 'Norpregnenes', 'Norsteroids', 'Progestin Contraceptives', 'Progestins', 'Progestogens and Estrogens, Sequential Preparations', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'UGT1A1 Inducers']" +DB00312,Pentobarbital,"Pentobarbitalis a barbiturate drug used to induce sleep, cause sedation, and control certain types of seizures.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P43681', 'P36544', 'P42262', 'Q13002', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'O75469']","Pentobarbital, a barbiturate, is used for the treatment of short term insomnia. It belongs to a group of medicines called central nervous system (CNS) depressants that induce drowsiness and relieve tension or nervousness. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.",CCCC(C)C1(CC)C(=O)NC(=O)NC1=O,"Pentobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGABA(A) Receptorpositive allosteric modulatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumansUNMDA receptorantagonistHumansUNuclear receptor subfamily group I member activatorHumans","['Anesthetic premedication therapy', 'Emergency Care']","['Adjuvants, Anesthesia', 'Anticholinergic Agents', 'Anticonvulsants', 'Barbiturates', 'Barbiturates, Plain', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2A6 Inducers (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones']" +DB01576,Dextroamphetamine,Dextroamphetamineis a sympathomimetic agent used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.,"['Q05940', 'P23975', 'Q01959', 'Q96RJ0', 'P35368', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Dextroamphetamine is a noncatecholamine, sympathomimetic amine that acts as a CNS stimulant.LabelDextroamphetamine raises systolic and diastolic blood pressure, acts as a weak bronchodilator, and also acts as a respiratory stimulant.LabelThe general mechanism of action of dextroamphetamine has not been well established.Label",C[C@H](N)CC1=CC=CC=C1,"The exact mechanism of amphetamines as a class is not known. Dextroamphetamine acts by preventing reuptake, increasing release, and stimulating reverse-transport of dopamine in synaptic clefts in the striatum.Newer evidence shows amphetamines may also alter the number of dopamine transporters in synaptic clefts.TargetActionsOrganismASynaptic vesicular amine transporterinducerHumansASodium-dependent noradrenaline transporternegative modulatorHumansASodium-dependent dopamine transporternegative modulatorHumansUTrace amine-associated receptor agonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha adrenergic receptorinhibitorinducerHumans",[],"['Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Amphetamines', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Centrally Acting Sympathomimetics', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Ethylamines', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Phenethylamines', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetics']" +DB00457,Prazosin,Prazosinis an alpha-blocker that causes a decrease in total peripheral resistance and is used to treat hypertension.,"['P35348', 'P35368', 'P25100', 'Q12809', 'P08913', 'P18089', 'P35348', 'P35368', 'P25100']","Effects on blood pressureThe pharmacodynamic and therapeutic effect of this drug includes is a decrease in blood pressure as well as clinically significant decreases in cardiac output, heart rate, blood flow to the kidney, and glomerular filtration rate. The decrease in blood pressure may occur in both standing and supine positionsLabel.Many of the above effects are due to vasodilation of blood vessels caused by prazosin, resulting in decreased peripheral resistance7,Label. Peripheral resistance refers to the level resistance of the blood vessels to blood that flows through them. As the blood vessels constrict (narrow), the resistance increases and as they dilate (widen), and peripheral resistance decreases, lowering blood pressure14,17.Effects on sleep disturbance related to post-traumatic stress disorder (PTSD)Some studies have suggested that this drug improves sleep in patients suffering from insomnia related to nightmares and post-traumatic stress disorder, caused by hyperarousal5,6. This effect likely occurs through the inhibition of adrenergic stimulation found in states of hyperarousal13.",COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1=CC=CO1,"Alpha-adrenergic receptors are essential for the regulation of blood pressure in humans. Two types of alpha receptors, alpha and alpha , both play a role in regulating blood pressure. Alpha- receptors are postsynaptic (located after the nerve junction, or space between a nerve fiber and target tissue). In this case, the target tissue is the vascular smooth muscle. These receptors, when activated, increase blood pressure.Prazosin inhibits the postsynaptic alpha- adrenoceptors. This inhibition blocks the vasoconstricting (narrowing) effect of catecholamines (epinephrine and norepinephrine) on the vessels, leading to peripheral blood vessel dilation. Through blood vessel constriction by adrenergic receptor activation, epinephrine and norepinephrine normally act to increase blood pressure.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAAlpha-D adrenergic receptorantagonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUAlpha-A adrenergic receptorbinderHumansUAlpha-B adrenergic receptorbinderHumansUAlpha- adrenergic receptorsNot AvailableHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Alpha-Adrenoreceptor Antagonists and Diuretics', 'Antiadrenergic Agents, Peripherally Acting', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'BCRP/ABCG2 Substrates', 'Cardiovascular Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral alpha-1 blockers', 'Quinazolines', 'Vasodilating Agents']" +DB00747,Scopolamine,Scopolamineis a belladonna alkaloid with anticholinergic effects indicated for the treatment of nausea and vomiting associated with motion sickness and postoperative nausea and vomiting (PONV).,"['P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P43681', 'P17787', 'P14410']","Scopolamine is an anticholinergic belladonna alkaloid that, through competitive inhibition of muscarinic receptors, affects parasympathetic nervous system function and acts on smooth muscles that respond to acetylcholine but lack cholinergic innervation. Formulated as a patch, scopolamine is released continuously over three days and remains detectable in urine over a period of 108 hours. Scopolamine is contraindicated in angle-closure glaucoma and should be used with caution in patients with open-angle glaucoma due to scopolamine's ability to increase intraocular pressure. Also, scopolamine exhibits several neuropsychiatric effects: exacerbated psychosis, seizures, seizure-like, and other psychiatric reactions, and cognitive impairment; scopolamine may impair the ability of patients to operate machinery or motor vehicles, play underwater sports, or perform any other potentially hazardous activity. Women with severe preeclampsia should avoid scopolamine. Patients with gastrointestinal or urinary disorders should be monitored frequently for impairments, and scopolamine should be discontinued if these develop. Scopolamine can cause blurred vision if applied directly to the eye, and the transdermal patch should be removed before an MRI procedure to avoid skin burns. Due to its gastrointestinal effects, scopolamine can interfere with gastric secretion testing and should be discontinued at least 10 days before performing the test. Finally, scopolamine may induce dependence and resulting withdrawal symptoms, such as nausea, dizziness, vomiting, gastrointestinal disturbances, sweating, headaches, bradycardia, hypotension, and various neuropsychiatric manifestations following treatment discontinuation; severe symptoms may require medical attention.9",CN1[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1,"Acetylcholine(ACh) is a neurotransmitter that can signal through ligand-gated cation channels (nicotinic receptors) and G-protein-coupled muscarinic receptors (mAChRs). ACh signalling via mAChRs located in the central nervous system (CNS) and periphery can regulate smooth muscle contraction, glandular secretions, heart rate, and various neurological phenomena such as learning and memory.,mAChRs can be divided into five subtypes, M-M, expressed at various levels throughout the brain.Also, M receptors are found in the heart and M receptors in smooth muscles, mediating effects apart from the direct modulation of the parasympathetic nervous system.While M, M, and M mAChRs primarily couple to Gqproteins to activate phospholipase C, M and M mainly couple to Gi/oproteins to inhibit adenylyl cyclase and modulate cellular ion flow.This system, in part, helps to control physiological responses such as nausea and vomiting.Scopolamine acts as a non-selective competitive inhibitor of M-M mAChRs, albeit with weaker M inhibition; as such, scopolamine is an anticholinergic with various dose-dependent therapeutic and adverse effects.,,The exact mechanism(s) of action of scopolamine remains poorly understood. Recent evidence suggests that M (and possibly M) mAChR antagonism at interneurons acts through inhibition of downstream neurotransmitter release and subsequent pyramidal neuron activation to mediate neurological responses associated with stress and depression.Similar antagonism of M and M receptors is associated with potential therapeutic benefits in neurological conditions such as schizophrenia and substance abuse disorders.The significance of these observations to scopolamine's current therapeutic indications of preventing nausea and vomiting is unclear but is linked to its anticholinergic effect and ability to alter signalling through the CNS associated with vomiting.,TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansUNeuronal acetylcholine receptor subunit alpha-inhibitorinducerHumansUNeuronal acetylcholine receptor subunit beta-inhibitorinducerHumansUSucrase-isomaltase, intestinalinhibitorHumans",['Anesthetic premedication therapy'],"['Adjuvants', 'Adjuvants, Anesthesia', 'Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Alkaloids', 'Anticholinergic Agents', 'Antiemetics', 'Antiemetics and Antinauseants', 'Antimuscarinics Antispasmodics', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Belladonna Alkaloids', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Gastrointestinal Agents', 'Hypnotics and Sedatives', 'Muscarinic Antagonists', 'Mydriatics', 'Mydriatics and Cycloplegics', 'Nervous System', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Psycholeptics', 'Scopolamine Derivatives', 'Sensory Organs', 'Solanaceous Alkaloids', 'Tropanes']" +DB01221,Ketamine,Ketamineis a rapid-acting general anesthetic and NMDA receptor antagonist used for induction of anesthesia diagnostic and surgical procedures typically in combination with a muscle relaxant.,"['Q8TCU5', 'P46098', 'Q693P7', 'P06276', 'P29475', 'P25103', 'P14416', 'P41143', 'P23975', 'P41145', 'P35372', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P28223', 'P41595', 'P28335', 'P08908', 'P28222', 'P28221', 'P28566', 'P30939']","Ketamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression. The anesthetic state produced by Ketamine has been termed as ""dissociative anesthesia"" in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticular-activating and limbic systems).2Ketamine enhances descending inhibiting serotoninergic pathways and can exert antidepressive effects. These effects are seen in concentrations ten times lower than the needed concentration for anesthetic proposes. The effect of ketamine can be described as analgesic by the prevention of central sensitization in dorsal horn neurons as well as by the inhibition on the synthesis of nitric oxide. Ketamine can present cardiovascular changes and bronchodilatation.9",CNC1(CCCCC1=O)C1=CC=CC=C1Cl,"Ketamine interacts with N-methyl-D-aspartate (NMDA) receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Unlike other general anaesthetic agents, ketamine does not interact with GABA receptors.TargetActionsOrganismAGlutamate receptor ionotropic, NMDA AantagonistHumansA-hydroxytryptamine receptor ApotentiatorHumansAAlpha- nicotinic cholinergic receptor subunitantagonistHumansACholinesteraseinhibitorHumansANitric oxide synthase, braininhibitorHumansUNeurokinin receptorantagonistHumansUDopamine D receptoragonistpartial agonistHumansUDelta-type opioid receptorbinderHumansUSodium-dependent noradrenaline transporterinhibitorHumansUKappa-type opioid receptoragonistHumansUMu-type opioid receptorbinderHumansUMuscarinic acetylcholine receptorbinderHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor antagonistHumans","['General Anesthesia', 'Induction and Maintenance of General Anesthesia']","['Agents producing tachycardia', 'Amino Acids', 'Amino Acids, Acidic', 'Amino Acids, Dicarboxylic', 'Amino Acids, Peptides, and Proteins', 'Analgesics', 'Anesthetics', 'Anesthetics, Dissociative', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Cyclohexanes', 'Cycloparaffins', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Excitatory Amino Acid Agents', 'Excitatory Amino Acid Agonists', 'Excitatory Amino Acid Antagonists', 'Miscellaneous General Anesthetics', 'N-Methylaspartate, agonists', 'Nervous System', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Vasodilating Agents']" +DB00144,Phosphatidyl serine,Phosphatidyl serineis a nutrient used in some supplement products.,"['Q9UG56', 'Q8WTV0', 'P17252', 'P48651', 'P49619', 'Q16760', 'Q9BVG9', 'Q9NXE4', 'Q9NY59', 'Q9Y2Q0']","Phosphatidylserine is indicated in the treatment of cognitive impairment, including Alzheimer's disease, age-associated memory impairment and some non-Alzheimer's dementias. Further research is required before phosphatidylserine can be indicated for immune enhancement or for reduction of exercise stress. Phosphatidylserine was first isolated from brain lipids called cephalins. The major cephalins are phosphatidylserine and phophatidylethanolamine. Phosphatidylserine is involved in signal transduction activity as well as being a basic structural component of biologic membranes.",CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC,"Cholinergic hypofunction is thought to account in part for the cognitive deficits found in Alzheimer's disease. The most commonly used drugs for the treatment of Alzheimer's disease are reversible acetylcholinesterase inhibitors. The rationale of these drugs is to increase acetylcholine levels in the brains of Alzheimer's patients, and they may be somewhat effective in some cases. Phosphatidylserine restores acetylcholine release in aging humans by maintaining an adequate supply of the molecule and is able to increase the availability of endogenous choline for de novo acetylcholine synthesis. The hippocampus of the brain is believed to be important for cognitive processes and is affected in those with Alzheimer's disease. The dendritic spines of pyramidal cells, the post-synaptic target of the excitatory input to the hippocampus, have been proposed as a substrate for information storage. Age-dependent dendritic spine loss in pyramidal neurons has been reported in the human brain, and the extent of synaptic loss appears to correlate with the degree of cognitive impairment. Phosphatidylserine treatment prevents the age-related reduction in dendritic spine density in rat hippocampus. Protein kinase C facilitation of acetylcholine release has been reported in rats. Phosphatidylserine was found to restore protein kinase C activity in aging rats. Stimulation of calcium uptake by brain synaptosomes and activation of protein kinase C are yet other speculative mechanisms of phosphatidylserine's putative cognition-enhancing action.TargetActionsOrganismUPhosphatidylserine decarboxylase proenzymeNot AvailableHumansUScavenger receptor class B member Not AvailableHumansUProtein kinase C alpha typeNot AvailableHumansUPhosphatidylserine synthase Not AvailableHumansUDiacylglycerol kinase gammaNot AvailableHumansUDiacylglycerol kinase deltaNot AvailableHumansUPhosphatidylserine synthase Not AvailableHumansUSphingomyelin phosphodiesterase Not AvailableHumansUSphingomyelin phosphodiesterase Not AvailableHumansUProbable phospholipid-transporting ATPase IANot AvailableHumans",[],"['Dietary Supplements', 'Glycerophosphates', 'Glycerophospholipids', 'Lipids', 'Membrane Lipids', 'Phosphatidic Acids', 'Phosphatidylserines', 'Phospholipids', 'Supplements']" +DB00395,Carisoprodol,Carisoprodolis a centrally acting muscle relaxant used to relieve the discomfort associated with various musculoskeletal conditions.,"['P14867', 'P47870', 'P18507', 'P31644', 'P34903']","Carisoprodol is a centrally acting skeletal muscle relaxant that does not act directly on skeletal muscle but acts directly on the central nervous system (CNS). This drug relieves the painful effects of muscle spasm12,19. A metabolite of carisoprodol,meprobamate, possesses both anxiolytic and sedative propertiesLabel. Clinical studies have shown that this drug causes impairment of psychomotor performance in neuropsychological tests.5,10",CCCC(C)(COC(N)=O)COC(=O)NC(C)C,"The mechanism of action of carisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been confirmed. +In studies using animal models, the muscle relaxation that is induced by carisoprodol is associated with a change in the interneuronal activity of the spinal cord and of the descending reticular formation, located in the brain.LabelThe abuse potential of this drug is attributed to its ability to alter GABAA function.This drug has been shown to modulate a variety of GABAA receptor subunits.,GABAA receptor modulation can lead to anxiolysis due to inhibitory effects on neurotransmission.TargetActionsOrganismUGamma-aminobutyric acid receptor subunit alpha-activatormodulatorHumansUGamma-aminobutyric acid receptor subunit beta-modulatorHumansUGamma-aminobutyric acid receptor subunit gamma-Not AvailableHumansUGamma-aminobutyric acid receptor subunit alpha-modulatorHumansUGamma-aminobutyric acid receptor subunit alpha-modulatorHumans",[],"['Carbamates', 'Carbamic Acid Esters', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally-mediated Muscle Relaxation', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 Substrates', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System']" +DB01544,Flunitrazepam,Flunitrazepamis a benzodiazepine used to manage anxiety disorders and insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Flunitrazepam is a powerful hypnotic drug that is a benzodiazepine derivative. It has powerful hypnotic, sedative, anxiolytic, and skeletal muscle relaxant properties. The drug is sometimes used as a date rape drug. In the United States, the drug has not been approved by the Food and Drug Administration for medical use, and is considered to be an illegal drug. It has however been approved in the United Kingdom and other countries.",CN1C2=C(C=C(C=C2)[N+]([O-])=O)C(=NCC1=O)C1=CC=CC=C1F,"Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ, which mediates sleep, and BNZ, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'UGT1A1 Inhibitors', 'UGT1A3 Inhibitors', 'UGT2B7 Inhibitors']" +DB00228,Enflurane,Enfluraneis a halogenated inhalational anesthetic agent used for the induction and maintenance of anesthesia and for analgesia during labor and delivery.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'Q06432', 'Q9Y698', 'O60359', 'Q9UBN1', 'Q9UF02', 'Q9BXT2', 'P62955', 'Q8WXS5', 'P54289', 'Q9NY47', 'Q8IZS8', 'Q7Z3S7', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'Q00975', 'O00555', 'Q15878', 'O43497', 'O95180', 'Q9P0X4', 'P23415', 'Q09470', 'Q16322', 'P16389', 'P22001', 'P22459', 'P22460', 'P17658', 'Q14721', 'Q92953', 'P48547', 'Q96PR1', 'Q14003', 'Q03721', 'Q9NSA2', 'Q9NZV8', 'Q9UK17', 'P15382', 'Q9Y6J6', 'Q9Y6H6', 'Q8WWG9', 'Q9UJ90', 'Q9H3M0', 'Q9UIX4', 'Q9UJ96', 'Q8TAE7', 'Q8TDN1', 'O95259', 'Q12809', 'Q9ULD8', 'Q9UQ05', 'Q8NCM2', 'Q9H252', 'Q9NS40', 'Q96L42', 'P51787', 'O43526', 'O43525', 'P56696', 'Q9NR82', 'Q96KK3', 'Q9BQ31', 'Q6PIU1', 'Q8TDN2', 'Q14722', 'Q13303', 'P98194', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'O14983']","Enflurane rapidly induces anesthesia via the stimulation of inhibitory neural channels and the inhibition of excitatory neural channels. Muscle relaxation, obtundation of pharyngeal and laryngeal reflexes, and lowering of blood pressure are some of the main pharmacodynamic effects of this drug.17Enflurane also decreases cardiac muscle contractility.5High concentrations of enflurane may lead to uterine relaxation and increase the risk of uterine bleeding during delivery.17Rare but clinically significant elevations in ALT may indicate hepatoxicity from the use of enflurane.3In some susceptible patients, enflurane may cause malignant hyperthermia.17",FC(F)OC(F)(F)C(F)Cl,"The mechanism of action of enflurane is not completely established.Studies on rats indicate that enflurane binds to GABAA and glycine receptors, causing depressant effects at the ventral neural horn. It has been reported that % of the central nervous system depressant effects on the spinal cord after enflurane is administered are caused by the (GABA-A) receptor while binding to glycine receptors is responsible for about % of the depressant effects.The relevance of these findings to humans is unknown. Other studies have found that enflurane binds to the calcium channels in the cardiac sarcoplasmic reticulum causing cardio depressant effects.,,Other studies support that this drug potentiates glycine receptors, which results in central nervous system depressant effects.,TargetActionsOrganismAGABA(A) ReceptorpotentiatorHumansAVoltage-dependent calcium channelinhibitoractivatorHumansAGlycine receptor subunit alpha-potentiatorHumansUVoltage-gated Potassium ChannelsinhibitoractivatorUCalcium-transporting ATPase type C member inhibitorHumansUGlutamate (NMDA) receptorantagonistHumansUSarcoplasmic/endoplasmic reticulum calcium ATPase inhibitorstimulatorHumans",['Cesarean Sections'],"['Agents that reduce seizure threshold', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Inhalation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Substrates', 'Ethers', 'Methyl Ethers', 'Nervous System']" +DB00714,Apomorphine,"Apomorphineis a morphine derivative D2 dopamine agonist used to treat hypomobile ""off"" episodes of advanced Parkinson's disease.","['P21917', 'P14416', 'P35462', 'P21918', 'P21728', 'P18825', 'P18089', 'P08908', 'P28223', 'P41595', 'P28335', 'P08913', 'P28221', 'P28222']","Apomorphine is a dopaminergic agonist that may stimulate regions of the brain involved in motor control.8,11,12It has a short duration of action and a wide therapeutic index as large overdoses are necessary for significant toxicity.11,12Patients should be counselled regarding the risk of nausea, vomiting, daytime somnolence, hypotension, oral mucosal irritation, falls, hallucinations, psychotic-like behaviour, impulsive behaviour, withdrawal hyperpyrexia, and prolongation of the QT interval.11,12Given the incidence of nausea and vomiting in patients taking apomorphine, treatment withtrimethobenzamidemay be recommended prior to or during therapy. Antiemetic pretreatment may be started three days prior to beginning therapy with apomorphine - it should only be continued as long as is necessary and generally for no longer than two months.15",[H][C@]12CC3=C(C(O)=C(O)C=C3)C3=CC=CC(CCN1C)=C23,"Apomorphine is a non-ergoline dopamine agonist with high binding affinity to dopamine D, D, and D receptors.,Stimulation of D receptors in the caudate-putamen, a region of the brain responsible for locomotor control, may be responsible for apomorphine's action.However, the means by which the cellular effects of apomorphine treat hypomobility of Parkinson's remain unknown.,TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansUAlpha-C adrenergic receptoragonistHumansUAlpha-B adrenergic receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor CagonistHumansUAlpha-A adrenergic receptoragonistHumansU-hydroxytryptamine receptor DagonistHumansU-hydroxytryptamine receptor BagonistHumans",[],"['Alkaloids', 'Anti-Parkinson Agents (Dopamine Agonist)', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Aporphines', 'Autonomic Agents', 'Benzylisoquinolines', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'COMT Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Drugs Used in Erectile Dysfunction', 'Emetics', 'Gastrointestinal Agents', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Isoquinolines', 'Nervous System', 'Neurotransmitter Agents', 'Nonergot-derivative Dopamine Receptor Agonists', 'Opiate Agonists', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Urologicals']" +DB09282,Molsidomine,"Molsidomineis a long-acting vasodilator used to treat angina pectoris, including in association with left heart failure and acute myocardial infarction.",['P33402'],"Molsidomine leads to smooth muscle relaxation in the coronary blood vessels, relieving symptoms of angina and increasing blood flow to the coronary arteries.",CCOC(=O)[N-]C1=C[N+](=NO1)N1CCOCC1,"Molsidomine, a cardiovascular drug, acts in a similar fashion to organic nitrates. The SIN-A metabolite of molsidomine has a pharmacologically active group of nitric oxide, which increases levels of cyclic GMP, and decreases intracellular calcium ions in smooth muscle cells. This leads to relaxation of smooth muscle in the blood vessels, and inhibits platelet aggregation.TargetActionsOrganismUGuanylate cyclase soluble subunit alpha-agonistHumans",[],"['Cardiac Therapy', 'Cardiovascular Agents', 'Morpholines', 'Nitric Oxide Donors', 'Oxadiazoles', 'Oxazines', 'Oxazoles', 'Sydnones', 'Vasodilating Agents', 'Vasodilators Used in Cardiac Diseases']" +DB00185,Cevimeline,Cevimelineis a muscarinic agonist with parasympathomimetic activities that is used for the symptomatic treatment of dry mouth in patients with Sjögren's Syndrome.,"['P20309', 'P11229']","Cevimeline is a cholinergic agonist which binds to muscarinic receptors. Muscarinic agonists in sufficient dosage can increase secretion of exocrine glands, such as salivary and sweat glands and increase tone of the smooth muscle in the gastrointestinal and urinary tracts.",CC1O[C@@]2(CS1)CN1CCC2CC1,"Muscarinic agonists such as cevimeline bind and activate the muscarinic M and M receptors. The M receptors are common in secretory glands (exocrine glands such as salivary and sweat glands), and their activation results in an increase in secretion from the secretory glands. The M receptors are found on smooth muscles and in many glands which help to stimulate secretion in salivary glands, and their activation generally results in smooth muscle contraction and increased glandular secretions. Therefore, as saliva excretion is increased, the symptoms of dry mouth are relieved.TargetActionsOrganismAMuscarinic acetylcholine receptor MagonistHumansAMuscarinic acetylcholine receptor MagonistHumans",[],"['Autonomic Agents', 'Cholinergic Agents', 'Cholinergic Agonists', 'Cholinergic Receptor Agonist', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Muscarinic Agonists', 'Nervous System', 'Neurotransmitter Agents', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Sulfur Compounds']" +DB01164,Calcium chloride,"Calcium chlorideis an ionic compound used for the treatment of hypocalcemia and hyperkalemia, and as an antidote to magnesium intoxication due to overdosage of magnesium sulfate.",['Q99584'],"Calcium is the fifth most abundant element in the body and the major fraction is in the bony structure. Calcium plays important physiological roles, many of which are poorly understood. It is essential for the functional integrity of the nervous and muscular systems. It is necessary for normal cardiac function and is one of the factors that operates in the mechanisms involved in the coagulation of blood.",[Cl-].[Cl-].[Ca++],"Calcium chloride in water dissociates to provide calcium (Ca+) and chloride (Cl-) ions. They are normal constituents of the body fluids and are dependent on various physiological mechanisms for maintenance of balance between intake and output. For hyperkalemia, the influx of calcium helps restore the normal gradient between threshold potential and resting membrane potential.TargetActionsOrganismUProtein S-ANot AvailableHumans","['Continuous Renal Replacement Therapy', 'Electrolyte replacement', 'Haemodiafiltration', 'Haemofiltration', 'Hemodialysis Treatment', 'Irrigation therapy', 'Parenteral Nutrition', 'Peritoneal dialysis therapy', 'Plasma Volume Replacement', 'Urine alkalinization therapy', 'Distension of the joints', 'Extraocular irrigation', 'Fluid and electrolyte maintenance therapy', 'Induction of cardiac arrest', 'Irrigation of the joints']","['Acidifying Agents', 'Alimentary Tract and Metabolism', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Calcium Compounds', 'Calcium Salts', 'Chlorides', 'Chlorine Compounds', 'Electrolyte Solutions', 'Genito Urinary System and Sex Hormones', 'Hemodialysis Solution', 'I.V. Solution Additives', 'Mineral Supplements', 'Replacement Preparations', 'Supplements', 'Urologicals']" +DB00122,Choline,Cholineis a nutrient found in a wide variety of vitamins including pre-natal formulations.,"['P36544', 'Q9Y5K3', 'P22303', 'P49585', 'O14939', 'P06276', 'Q13393', 'Q8TCT1']","This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). Choline is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Choline also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Choline has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Choline deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth.",C[N+](C)(C)CCO,"Choline is a major part of the polar head group of phosphatidylcholine. Phosphatidylcholine's role in the maintenance of cell membrane integrity is vital to all of the basic biological processes: information flow, intracellular communication and bioenergetics. Inadequate choline intake would negatively affect all these processes. Choline is also a major part of another membrane phospholipid, sphingomyelin, also important for the maintenance of cell structure and function. It is noteworthy and not surprising that choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an increase in ceramide, a precursor, as well as a metabolite, of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate Caspase, a type of enzyme that mediates apoptosis. Betaine or trimethylglycine is derived from choline via an oxidation reaction. Betaine is one of the factors that maintains low levels of homocysteine by resynthesizing L-methionine from homocysteine. Elevated homocysteine levels are a significant risk factor for atherosclerosis, as well as other cardiovascular and neurological disorders. Acetylcholine is one of the major neurotransmitters and requires choline for its synthesis. Adequate acetylcholine levels in the brain are believed to be protective against certain types of dementia, including Alzheimer's disease.TargetActionsOrganismUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUCholine-phosphate cytidylyltransferase Bproduct ofHumansUAcetylcholinesteraseproduct ofHumansUCholine-phosphate cytidylyltransferase Aproduct ofHumansUPhospholipase Dproduct ofHumansUCholinesteraseproduct ofHumansUPhospholipase Dproduct ofHumansUPhosphoethanolamine/phosphocholine phosphataseproduct ofHumans",['Nutritional supplementation'],"['Alcohols', 'Amines', 'Amino Alcohols', 'Analgesics', 'Antimetabolites', 'Central Nervous System Agents', 'Dietary Supplements', 'Ethanolamines', 'Gastrointestinal Agents', 'Hypolipidemic Agents', 'Lipid Regulating Agents', 'Lipotropic Agents', 'Nervous System', 'Nootropic Agents', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Onium Compounds', 'Other Nutritional Agents', 'Quaternary Ammonium Compounds', 'Salicylic Acid and Derivatives', 'Supplements', 'Trimethyl Ammonium Compounds', 'Vitamin B Complex', 'Vitamins']" +DB04841,Flunarizine,Flunarizineis a selective calcium-entry blocker used as migraine prophylaxis in patients with severe and frequent episodes who have not responded adequately to more common treatments.,"['O43497', 'O95180', 'Q9P0X4', 'P0DP23', 'P35367']",Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity.,FC1=CC=C(C=C1)C(N1CCN(C\C=C\C2=CC=CC=C2)CC1)C1=CC=C(F)C=C1,"Flunarizine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.TargetActionsOrganismAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansACalmodulinantagonistHumansUHistamine H receptorantagonistHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Anticonvulsants', 'Antimigraine Agents, Miscellaneous', 'Antivertigo Preparations', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Piperazine Derivatives', 'Piperazines', 'Vasodilating Agents']" +DB00368,Norepinephrine,Norepinephrineis a sympathomimetic used in the control of blood pressure during various hypotensive states and as an adjunct treatment during cardiac arrest.,"['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945', 'P00439', 'Q05940', 'P54219']",Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance.,NC[C@H](O)C1=CC(O)=C(O)C=C1,Norepinephrine functions as a peripheral vasoconstrictor by acting on alpha-adrenergic receptors. It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it's activity at the beta-adrenergic receptors.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-D adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-C adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansNPhenylalanine--hydroxylaseinhibitorHumansUSynaptic vesicular amine transporterbinderHumansUChromaffin granule amine transporterbinderHumans,[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Adrenergic beta-1 Receptor Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-3 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Alpha-and Beta-adrenergic Agonists', 'Amines', 'Amino Alcohols', 'Autonomic Agents', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'COMT Substrates', 'Epinephrine and similars', 'Ethanolamines', 'Neurotransmitter Agents', 'Norepinephrine, antagonists & inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Peripheral Nervous System Agents', 'Phenols', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB13345,Dihydroergocristine,Dihydroergocristineis an ergot alkaloid used to delay progressive mental decline in conditions like Alzheimer's.,"['P08908', 'P28222', 'P28221', 'P28566', 'P30939', 'P28223', 'P41595', 'P28335', 'P46098', 'O95264', 'Q8WXA8', 'Q70Z44', 'A5X5Y0', 'Q13639', 'P50406', 'P34969', 'P08588', 'P07550', 'P13945', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P21728', 'P21918', 'P14416', 'P35462', 'P21917']","Dihydroergocristine has been shown to present effect on memory and cognition. This activity in the brain is been reported by an increase in glutathione in age-related brain states.2The reported effect on serotonin and adrenergic receptors has also been correlated to an inhibition of platelet aggregation.8It has also been reported that individuals exposed to dihydroergocristine may present an amphoteric vasoregulating activity either hypotensive in hypertensive individuals or hypertensive in hypotensive individuals.1This action is performed by promoting a dilating action in the contracted arteries and a tonic action in the dilated arteries and arterioles.8The vasoregulating effect causes an increase in cerebral blood flow and oxygen consumption by the brain, which correlates with the brain protective function of dihydroergocristine.2In Alzheimer studies, dihydroergocristine reduced the amyloid-beta levels in different cell types.4To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visitErgoloid mesylate.",[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)(O[C@@]21O)C(C)C,"Dihydroergocristine mechanism of action seems to be related to a noncompetitive antagonistic activity in the serotonin receptors as well as a double partial agonist/antagonist activity in dopaminergic and adrenergic receptors.In Alzheimer studies, dihydroergocristine act as a direct inhibitor of γ-secretase.TargetActionsOrganismASerotonin ReceptorsantagonistHumansABeta adrenergic receptorantagonistagonistHumansAAlpha adrenergic receptorantagonistagonistHumansADopamine receptorantagonistagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Alkaloids', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Ergot Alkaloids and Derivatives', 'Ergotamines', 'Heterocyclic Compounds, Fused-Ring', 'Neurotransmitter Agents', 'Peripheral Vasodilators', 'Vasodilating Agents']" +DB00231,Temazepam,"Temazepamis a short-acting benzodiazepine commonly used to treat panic disorders, severe anxiety, and insomnia.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Temazepam is a benzodiazepine used as a hypnotic agent in the management of insomniaLabel6,7,12,13,14. Temazepam produces CNS depression at limbic, thalamic, and hypothalamic levels of the CNS6,7,13,14. Temazepam increases the affinity of the neurotransmitter gamma-aminobutyric acid (GABA) for GABA receptors by binding to benzodiazepine receptors6,7,13,14. Results are sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action6,7,13,14.In sleep laboratory studies, the effect of temazepam was compared to placebo during a two week period13. The studies demonstrated a linear dose-response improvement in total sleep time and sleep latency with substantial drug-placebo differences apparent for total sleep time and for sleep latency at higher doses of temazepam13. Regardless, REM sleep was ultimately unchanged but slow wave sleep was decreased13.Moreover, a transient syndrome, known as ""rebound insomnia"", wherein the symptoms that led to treatment with temazepam in the first place recur in an enhanced form, may happen on withdrawal of temazepam treatment13. The possibility of this occurrence is in part why long term use of temazepam is not recommended due to worries over tolerance and dependence wherein patients' bodies become physiologically accustomed to the regular presence and pharmacological effect of higher and higher doses of the benzodiazepine used13.The duration of hypnotic effect and the profile of unwanted adverse effects may be influenced by the distribution and elimination half-lives of the administered temazepam and any active metabolites that may be formed13. When such half-lives are long, the drug or its metabolite(s) may accumulate during periods of nightly administration and be associated with impairments of cognitive and motor performance during waking hours13. Conversely, if half-lives are short, the drug and metabolites would be cleared before the next dose is ingested, and carry-over effects related to sedation or CNS depression should be minimal or not present at all13. However, during nightly use and for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop - which may also contribute to the possibility of 'rebound insomnia'13.Consequently, if the drug has a very short elimination half-life, it is possible that a relative deficiency (for example, in relation to benzodiazepine GABA(a) receptor sites) may occur at some point in the interval between each night's use13. This sequence of events may account for certain clinical findings reported happening after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, including increased wakefulness during the last third of the night and the appearance of increased daytime anxiety13.",CN1C2=C(C=C(Cl)C=C2)C(=NC(O)C1=O)C1=CC=CC=C1,"Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body,,,. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors,,,. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons,,,.Subsequently, benzodiazepines like temazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors,,,. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors,,,. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells,,,. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action,,,.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansUGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00425,Zolpidem,Zolpidemis a sedative hypnotic used for the short-term treatment of insomnia to improve sleep latency.,"['P14867', 'P47869', 'P34903', 'P18507']","Effects on the central nervous system (CNS)This drug has CNS depressant effects, which may include somnolence, decreased alertness, sedation, drowsiness, dizziness, and other changes in psychomotor functionLabel. Due to the above effects, the FDA has recommended an initial dose of zolpidem (immediate-acting) is a single dose of 5 mg for women and a single dose of 5 or 10 mg for men, immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening14. Refer to product labeling for detailed information18,Label.Effects on memoryControlled studies in adults using objective measures of memory demonstrated no significant evidence of next-day memory impairment after the administration of zolpidem. On the contrary, in a clinical study involving the administration of zolpidem doses of 10 and 20 mg, a marked reduction in a next-morning recall of information relayed to subjects during peak drug effect (90 minutes after dosing) was observed. These subjects experienced a condition known asanterograde amnesia. Subjective evidence from adverse event data has suggested that anterograde amnesia may occur after zolpidem administration, mainly at doses above 10 mgLabel.Effects on psychomotor functionThis drug may cause decreased psychomotor performance. Additive psychomotor effects may occur with other drugs that cause depression of psychomotor function, including alcoholLabel. Patients taking zolpidem should be cautioned against participating in hazardous activities or occupations requiring complete mental alertness or motor coordination, including operating machinery or driving a motor vehicle after ingesting the drug. Potential impairment of the performance of the above types of activities may also occur the day after zolpidem ingestion, especially at higher doses and ingestion of the extended-release formLabel,18.Effects on insomnia and sleep stagesEvidence suggests that this drug is associated with minimal rebound insomnia. During clinical trials with patients using zolpidem on an ‘as-needed’ basis, zolpidem use resulted in global improvements in sleep6. Zolpidem has been demonstrated to decrease sleep latency (the time it takes to fall asleep) for up to 35 days in controlled clinical studiesLabel. In studies measuring the percentage of sleep time spent in each sleep stage, zolpidem has primarily been shown to preserve sleep stages. Sleep time spent in stages 3 and 4 (deep sleep) was measured as similar to placebo with only minor and inconsistent changes in REM (paradoxical) sleep at the recommended doseLabel.Next-day residual effectsIn 2013, the FDA issued a statement warning that patients who take zolpidem extended-release (Ambien CR)―either 6.25 mg or 12.5 mg―should not drive or participate in other activities requiring full mental alertness the day after taking the drug, due to the fact that zolpidem concentrations can remain increased the next day, and impair the ability to perform these activities14,18. Patients may decrease their risk of next-morning impairment by taking the lowest dose of their insomnia medicine that treats their symptoms, according to the FDA16. Specific dosing recommendations for both men and women are included in this statement14. This information is also available on product labeling18,Label.Rebound effectsThere was no polysomnographic (objective) evidence of rebound insomnia at normal doses, in studies evaluating sleep on the nights following discontinuation of zolpidem tartrate. Subjective evidence of impaired sleep in the elderly on the first post-treatment night was observed at doses higher than the recommended 5mg dose for elderly patientsLabel.",CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C1=CC=C(C)C=C1,"Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with aGABA-BZreceptor complex and shares various pharmacological properties with thebenzodiazepineclass of drugsLabel.Subunit binding of theGABAAreceptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of zolpidem. The main regulatory site of the GABAA receptor complex can be found on itsalpha (α) subunitand is called thebenzodiazepine(BZ) oromega (ω)receptor. At least three different subtypes of the (ω) receptor have been identified to this dateLabel.In contrast to benzodiazepine drugs, which are found to modulate all benzodiazepine receptor subtypes in a non-selective fashion, zolpidem binds the (BZ) receptor specifically with a potent affinity for the alpha /alpha subunits (in vitro)Label. More recent studies suggest that zolpidem binds primarily to the alpha , , and subunits of the GABA receptor,,, and not the alpha subunit.The (BZ) receptor is found primarily on the Lamina IV of the brain sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. Specific and selective binding of zolpidem on the (BZ) receptor is not considered absolute, however, this binding could potentially explain the relative lack of myorelaxant and anticonvulsant activity in animal studies in addition to the preservation of deep sleep (stages and ) in human studies of zolpidem at hypnotic dosesLabel.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansUGamma-aminobutyric acid receptor subunit alpha-agonistHumansUGamma-aminobutyric acid receptor subunit alpha-agonistHumansUGamma-aminobutyric acid receptor subunit gamma-agonistHumans",[],"['Benzodiazepine hypnotics and sedatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Central Nervous System Depression', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Agonists', 'GABA-A Receptor Agonists', 'gamma-Aminobutyric Acid-ergic Agonist', 'Hypnotics (Nonbenzodiazepine)', 'Hypnotics and Sedatives', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Pyridines', 'Sleep Aids, Pharmaceutical']" +DB01205,Flumazenil,"Flumazenilis a benzodiazepine antagonist that is used for the complete or partial reversal of the sedative effects caused by benzodiazepines in various clinical settings, such as induced general anesthesia for diagnostic and therapeutic procedures.","['P18507', 'P31644', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867']","Flumazenil antagonizes the CNS effects produced by benzodiazepines, but does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids.",CCOC(=O)C1=C2CN(C)C(=O)C3=C(C=CC(F)=C3)N2C=N1,"Flumazenil, an imidazobenzodiazepine derivative, is a benzodiazepine antagonist. It competitively inhibits the benzodiazepine binding site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit gamma-antagonistHumansAGamma-aminobutyric acid receptor subunit alpha-antagonistHumansAGABA(A) Receptorpositive allosteric modulatorHumansAGamma-aminobutyric acid receptor subunit alpha-antagonistHumans","['Anesthesia, Reversal', 'Reversal of sedation therapy']","['Antidotes', 'Benzazepines', 'Benzodiazepine Antagonist', 'Benzodiazepinones', 'Compounds used in a research, industrial, or household setting', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Miscellaneous Central Nervous System Agents', 'Neurotransmitter Agents', 'Protective Agents']" +DB00804,Dicyclomine,Dicyclomineis an antimuscarinic agent used to treat IBS.,"['P11229', 'P20309', 'P08172']",Dicyclomine is an anticholinergic drug used to relax the smooth muscles of the intestines.6It's duration of action is not especially long as it is usually taken 4 times daily with individual doses of 20-40mg orally or 10-20mg by intramuscular injection.6Dicyclomine should not be administered intravenously.6,CCN(CC)CCOC(=O)C1(CCCCC1)C1CCCCC1,"Dicyclomine achieves its action partially through direct antimuscarinic activity of the M, M, and M receptors; and partially through antagonism of bradykinin and histamine.,,,Dicyclomine non-competitively inhibits the action of bradykinin and histamine, resulting in direct action on the smooth muscle, and decreased strength of contractions seen in spasms of the ileum.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Acids, Carbocyclic', 'Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Anticholinergic Agents', 'Antimuscarinics Antispasmodics', 'Autonomic Agents', 'Cholinergic Agents', 'Cyclohexanecarboxylic Acids', 'Cyclohexanes', 'Cycloparaffins', 'Drugs for Functional Gastrointestinal Disorders', 'Drugs that are Mainly Renally Excreted', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Synthetic Anticholinergics, Esters With Tertiary Amino Group']" +DB00260,Cycloserine,Cycloserineis a broad-spectrum antibiotic used in the treatment of tuberculosis and certain urinary tract infections (UTI).,"['P0A6J8', 'Q9L888']","Cycloserine, a broad-spectrum antibiotic, may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. Cycloserine works by blocking the formation of these peptidoglycans. By doing this the walls of the bacteria become weak and it results in the death of the bacteria",N[C@@H]1CONC1=O,"Cycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis.TargetActionsOrganismAD-alanine--D-alanine ligase AinhibitorEscherichia coli (strain K)AAlanine racemaseinhibitorMycobacterium avium",[],"['Amino Acids', 'Amino Acids, Neutral', 'Amino Acids, Peptides, and Proteins', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibiotics, Antitubercular', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antimycobacterials', 'Drugs for Treatment of Tuberculosis', 'Isoxazoles', 'Neurotoxic agents', 'Noxae', 'Oxazoles', 'Oxazolidinones', 'Toxic Actions']" +DB04599,Aniracetam,Aniracetamis a nootropic drug used to ameliorate memory and attention disturbances accompanying cerebrovascular diseases and degenerative brain disorders.,"['P42262', 'P42263', 'P28223', 'P14416']","Aniracetam possesses a wide range of anxiolytic properties, which may be mediated by an interaction between cholinergic, dopaminergic and serotonergic systems.",COC1=CC=C(C=C1)C(=O)N1CCCC1=O,TargetActionsOrganismUGlutamate receptor Not AvailableHumansUGlutamate receptor Not AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumansUDopamine D receptorNot AvailableHumans,[],"['Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Nervous System', 'Nootropic Agents', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Psychotropic Drugs', 'Pyrrolidines']" +DB00629,Guanabenz,Guanabenzis an alpha-2 adrenergic agonist used to treat hypertension.,"['P08913', 'P18089']","Guanabenz, a centrally acting α-2 adrenergic agonist, is indicated for treatment of hypertension.",NC(N)=NN=CC1=C(Cl)C=CC=C1Cl,"Guanabenz's antihypertensive effect is thought to be due to central alpha-adrenergic stimulation, which results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature in addition to a decreased systolic and diastolic blood pressure and a slight slowing of pulse rate. Chronic administration of guanabenz also causes a decrease in peripheral vascular resistance.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansUAlpha-B adrenergic receptorbinderHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amidines', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Central alpha-2 Adrenergic Agonist', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Guanidines', 'Neurotransmitter Agents']" +DB03088,Pidolic acid,"Pidolic acid is a naturally occurring but little-studied amino acid derivative that can be formed enzymatically or non-enzymatically and participates as a biological intermediate with unique pharmacodynamics in various chemical pathways4,7. Elevations of the acid in blood levels may be associated with problems of glutamine or glutathione metabolism7. Pidolic acid, in general, is found in large quantities in brain tissue and other tissues in bound form, like skin7.","['P19961', 'P15692', 'P04746', 'P0CG04', 'P01709', 'Q03403', 'P00091', 'Q9UKQ2', 'Q7SIE2', 'O68601', 'Q701N4', 'O43612', 'P80075', 'P00138']","Pidolic acid is a naturally occurring but little-studied amino acid derivative that can be formed enzymatically or non-enzymatically and participates as a biological intermediate in various chemical pathways4,7. Elevations of the acid in blood levels may be associated with problems of glutamine or glutathione metabolism7. Pidolic acid, in general, is found in large quantities in brain tissue and other tissues in bound form, like skin7.Moreover, pidolic acid in high enough levels can act as an acidogen capable of inducing acidosis and a metabotoxin that can result in adverse health effects7. Chronically elevated levels of pidolic acid are associated with at least five inborn errors of metabolism including 5-oxoprolinuria (where 5-oxoproline is otherwise known as pidolic acid), 5-oxoprolinase deficiency, glutathione synthetase deficiency, hawkinsinuria, and propionic acidemia7. In particular, abnormally high levels of organic acids like pidolic acid in the blood, urine, brain, and/or other tissues results in general metabolic acidosis7. Such acidosis generally occurs when arterial pH falls below 7.357. In infants, the initial symptoms of acidosis consist of poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy7. Eventually, acidosis and the symptoms of acidosis can lead to heart, liver, and kidney abnormalities, seizures, coma, and possibly even death7. Many children who are afflicted with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures7.High levels of pidolic acid in the blood have also been demonstrated following acetaminophen overdose, causing an increased level of acidity called a high anion gap metabolic acidosis5.",OC(=O)[C@@H]1CCC(=O)N1,"Pidolic acid is an endogenous amino acid derivative where the free amino group of glutamic acid or glutamine cyclizes to generate a lactam,. Subsequently it is also a metabolite in the glutathione cycle that is converted to glutamate by the enzyme -oxoprolinase,. Moreover, N-terminal glutamic acid and glutamine residues can either spontaneously cyclize to become pidolic acid, or be enzymatically transformed by glutaminyl cyclases,. In particular, this is ultimately a form of N-termini that is a challenge for N-terminal sequencing using Edman chemistry, which necessitates a free primary amino group that is not present in pidolic acid,. Pyroglutamate aminopeptidase can restore a free N-terminus by cleaving off the pyroglutamate residue, however,.Additionally, pidolic acid and certain pidolic acid salts like calcium, magnesium, and potassium pidolic acid are sometimes used as skin or hair conditioning agents because of their humectant effects. In such humectant formulations, hydrophilic amine, hydroxyl, or even carboxyl groups possess high affinities for forming hydrogen bonds with molecules of water, allowing the hygroscopic formulations to attract and retain moisture in the air nearby through absorption, therefore drawing the water vapor into the formulation.TargetActionsOrganismUAlpha-amylase BNot AvailableHumansUVascular endothelial growth factor ANot AvailableHumansUPancreatic alpha-amylaseNot AvailableHumansUIg lambda- chain C regionsNot AvailableHumansUIg lambda chain V-II region MGCNot AvailableHumansUTrefoil factor Not AvailableHumansUCytochrome cNot AvailableRhodopseudomonas palustris (strain ATCC BAA- / CGA)UDisintegrin and metalloproteinase domain-containing protein Not AvailableHumansUEndo-,-beta-xylanaseNot AvailableBacillus agaradhaerensUDissimilatory copper-containing nitrite reductaseNot AvailableAlcaligenes xylosoxydans xylosoxydansUKeratin-associated protein -Not AvailableHumansUOrexinNot AvailableHumansUC-C motif chemokine Not AvailableHumansUCytochrome c'Not AvailableAlcaligenes xylosoxydans xylosoxydans",[],"['Alimentary Tract and Metabolism', 'Amino Acids', 'Amino Acids, Acidic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Glutamates', 'Imino Acids', 'Mineral Supplements', 'Pyrrolidines', 'Pyrrolidinones']" +DB00466,Picrotoxin,"A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the gamma-aminobutyric acid-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. [PubChem]","['P24046', 'P14867', 'P23416', 'O75311', 'P23415']","Picrotoxin is a toxin obtained from the seeds of the shrubAnamirta cocculus. It is used as a central nervous system stimulant, antidote, convulsant, and GABA (gamma aminobutyric acid) antagonist. It is a noncompetitive antagonist at GABAAreceptors and thus a convulsant. Picrotoxin blocks the GABAActivated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially barbiturates.",[H][C@@]12OC(=O)[C@@]34OC3C[C@@](O)(C3[C@@H](C1OC3=O)C(C)=C)[C@@]24C.[H][C@@]12C[C@@]3(O)C4[C@@H](C(OC4=O)[C@@]4([H])OC(=O)[C@]1(O2)[C@@]34C)C(C)(C)O,"Picrotoxin antagonizes the GABAAreceptor channel directly, which is a ligand-gated ion channel concerned chiefly with the passing of chloride ions across the cell membrane. Therefore picrotoxin prevents Cl-channel permeability and thus promtes an inhibitory influence on the target neuron. Picrotoxin reduces conductance through the channel by reducing not only the opening frequency but also the mean open time. Picrotoxin also antagonizes GABACreceptors (also called GABAA-rho receptors) but the result of this action is not known. The GABACreceptor is also linked to chloride channels, with distinct physiological and pharmacological properties. In contrast to the fast and transient responses elicited from GABAAreceptors, GABACreceptors mediate slow and sustained responses.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit rho-antagonistHumansAGamma-aminobutyric acid receptor subunit alpha-antagonistHumansUGlycine receptor subunit alpha-antagonistHumansUGlycine receptor subunit alpha-antagonistHumansUGlycine receptor subunit alpha-antagonistHumans",[],"['Antidotes', 'Biological Factors', 'Biological Products', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Complex Mixtures', 'Compounds used in a research, industrial, or household setting', 'Convulsants', 'Cyclohexanes', 'Cycloparaffins', 'GABA Agents', 'GABA Antagonists', 'GABA-A Receptor Antagonists', 'Lactones', 'Neurotransmitter Agents', 'Pharmaceutical Preparations', 'Plant Extracts', 'Plant Preparations', 'Protective Agents', 'Sesquiterpenes', 'Stimulants', 'Terpenes', 'Toxins, Biological']" +DB00235,Milrinone,"Milrinoneis a PDE-III inhibitor with inotropic, lusitropic, and vasodilatory properties used for the short-term treatment of acute decompensated heart failure.",['Q14432'],"Milrinone is a bipyridine derivative with positive inotropic and lusitropic effects that also results in peripheral vasodilation with minimal chronotropic effects over a therapeutic range of 100 to 300 ng/mL.8,6As such, milrinone is used in decompensated congestive heart failure.8Studies have demonstrated that milrinone exhibits sigmoidal effects, such that increasing milrinone plasma concentrations beyond a certain level results in no further hemodynamic changes.6Despite milrinone's benefits, both intravenous and oral use has been associated with increased frequency of ventricular arrhythmias, and long-term oral use has been associated with an increased risk of sudden death; in general, there are no data to support the safety or efficacy of milrinone use beyond 48 hours and patients should be monitored closely for cardiac dysfunction.8Also, as milrinone is primarily excreted renally, dose adjustments may be required in patients with impaired renal function.8",CC1=C(C=C(C#N)C(=O)N1)C1=CC=NC=C1,"Heart failure is a condition characterized by the heart's inability to provide adequate perfusion to the peripheral tissues, resulting in systemic symptoms including pulmonary, gastrointestinal, renal, and cerebral dysfunction.Although the biochemical and physiological processes underlying heart failure complex and variable, one such physiological response regulated by the sympathetic nervous system involves the eventual downregulation of cardiac β-receptors, decreased catecholamine sensitivity, and a corresponding decrease in adenylyl-cyclase-mediated signalling pathways.Increased intracellular cAMP, mainly acting through protein kinase A, increases sarcolemmal calcium release through L-type calcium channels as well as calcium re-uptake mediated by phospholamban and troponin I; these actions correspond to positive inotropic and lusitropic effects, respectively.,Milrinone is a partial competitive inhibitor of phosphodiesterase III (PDE-III), with a measured ICvalue of between . and . μM.,As a PDE-III inhibitor, milrinone results in an increase in intracellular cAMP, responsible for its pharmacological effects, including positive inotropy, positive lusitropy, and vasodilation.,,As milrinone affects cAMP levels through PDE-III and not through β-adrenergic receptors, it is effective in patients who have downregulated or otherwise desensitized β-adrenergic receptors and can be administered together with β-agonists/antagonists.,TargetActionsOrganismAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumans",[],"['Amines', 'Aminopyridines', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hematologic Agents', 'Phosphodiesterase 3 Inhibitors', 'Phosphodiesterase Inhibitors', 'Protective Agents', 'Pyridines', 'Vasodilating Agents']" +DB01003,Cromoglicic acid,"Cromoglicic acidis a medication used to treat asthma, allergic reactions of the eyes and nose, as well as other mast cell reactions.",['P25815'],"Cromoglicate or cromolyn (USAN), a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Cromoglicate is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis.",OC(COC1=CC=CC2=C1C(=O)C=C(O2)C(O)=O)COC1=CC=CC2=C1C(=O)C=C(O2)C(O)=O,"Cromoglicate inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Cromoglicate also may reduce the release of inflammatory leukotrienes. Cromoglicate may act by inhibiting calcium influx.TargetActionsOrganismUProtein S-PantagonistHumans",[],"['Adrenergics, Inhalants', 'Agents for Dermatitis, Excluding Corticosteroids', 'Alimentary Tract and Metabolism', 'Anti-Allergic Agents', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Antiallergic Agents, Excl. Corticosteroids', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Benzopyrans', 'Chromones', 'Cromolyn Sodium', 'Decongestants and Antiallergics', 'Decreased Histamine Release', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Drugs for Obstructive Airway Diseases', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Intestinal Antiinflammatory Agents', 'Mast Cell Stabilizers', 'Mast-cell Stabilizers', 'Nasal Preparations', 'Ophthalmologicals', 'Photosensitizing Agents', 'Pyrans', 'Respiratory System Agents', 'Sensory Organs']" +DB01176,Cyclizine,"Cyclizineis an antihistamine and antiemetic drug used for the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness, and vertigo.","['P35367', 'P49888']","Cyclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Cyclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which cyclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects.",CN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1,"Vomiting (emesis) is essentially a protective mechanism for removing irritant or otherwise harmful substances from the upper GI tract. Emesis or vomiting is controlled by the vomiting centre in the medulla region of the brain, an important part of which is the chemotrigger zone (CTZ). The vomiting centre possesses neurons which are rich in muscarinic cholinergic and histamine containing synapses. These types of neurons are especially involved in transmission from the vestibular apparatus to the vomiting centre. Motion sickness principally involves overstimulation of these pathways due to various sensory stimuli. Hence the action of cyclizine which acts to block the histamine receptors in the vomiting centre and thus reduce activity along these pathways. Furthermore since cyclizine possesses anti-cholinergic properties as well, the muscarinic receptors are similarly blocked.TargetActionsOrganismAHistamine H receptorantagonistHumansUEstrogen sulfotransferaseinhibitorHumans",[],"['Antiemetics', 'Antihistamines for Systemic Use', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Piperazine Derivatives', 'Piperazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00827,Cinoxacin,Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections.,['P43700'],"Cinoxacin is a synthetic antibacterial agent within vitroactivity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated.",CCN1N=C(C(O)=O)C(=O)C2=CC3=C(OCO3)C=C12,"Evidence exists that cinoxacin binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. It appears to also inhibit DNA gyrase. This enzyme is necessary for proper replicated DNA separation. By inhibiting this enzyme, DNA replication and cell division is inhibited.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNAintercalationHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'OAT1/SLC22A6 inhibitors', 'QTc Prolonging Agents', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00892,Oxybuprocaine,Oxybuprocaineis a local anesthetic used in ophthalmology.,['Q9Y5Y9'],"Oxybuprocaine is a local anaesthetic. It may be less irritating than tetracaine, and the onset and duration of action are similar to tetracaine.",CCCCOC1=CC(=CC=C1N)C(=O)OCCN(CC)CC,Oxybuprocaine binds to sodium channel and reversibly stabilizes the neuronal membrane which decreases its permeability to sodium ions. Depolarization of the neuronal membrane is inhibited thereby blocking the initiation and conduction of nerve impulses.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans,['Local Anesthesia of the Mouth'],"['Acids, Carbocyclic', 'Aminobenzoates', 'Anesthetics', 'Anesthetics for Topical Use', 'Anesthetics, Local', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase substrates', 'Dermatologicals', 'Local Anesthetics (Ester)', 'Ophthalmologicals', 'para-Aminobenzoates', 'Peripheral Nervous System Agents', 'Sensory Organs', 'Sensory System Agents']" +DB00626,Bacitracin,"Bacitracinis a cyclic polypeptide antibiotic used to prevent wound infections, treat pneumonia and empyema in infants, and to treat skin and eye infections.","['P14735', 'P01023']","Bacitracin is a mixture of polypeptides that prevent the formation of the bacterial cell wall and oxidatively cleave DNA.1It has a short duration of action as it must be given every 3 to 4 hours topically.10,11Bacitracin is nephrotoxic when given intramuscularly and may lead to renal failure.4",CC[C@H](C)[C@H](N)C1=N[C@@H](CS1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H]1CCCCNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](CCCN)NC1=O)[C@@H](C)CC,"Bacitracin binds to a divalent metal ion such as Mn(II), Co(II), Ni(II), Cu(II), or Zn(II).These complexes bind C-isoprenyl pyrophosphate, preventing the hydrolysis of a lipid dolichol pyrophosphate, which finally inhibits cell wall synthesis.Bacitracin metal complexes also bind and oxidatively cleave DNA.TargetActionsOrganismAC-isoprenyl pyrophosphateantagonistGram positive and gram negative bacteriaAInsulin-degrading enzymeinhibitorHumansUAlpha--macroglobulininhibitorHumans",[],"['Acids, Carbocyclic', 'Amino Acids, Peptides, and Proteins', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives for Systemic Use', 'Bacitracins', 'Benzene Derivatives', 'Benzoates', 'Decreased Cell Wall Synthesis & Repair', 'Dermatologicals', 'Hydroxy Acids', 'Hydroxybenzoates', 'Nephrotoxic agents', 'Peptides', 'Peptides, Cyclic', 'Phenols', 'Throat Preparations']" +DB01114,Chlorpheniramine,Chlorpheniramineis a histamine-H1 receptor antagonist indicated for the management of symptoms associated with upper respiratory allergies.,"['P35367', 'P31645', 'P23975', 'Q01959']","In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",CN(C)CCC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1,"Chlorpheniramine binds to the histamine H receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumansUSodium-dependent serotonin transporterinhibitorHumansUSodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumans",['Airway secretion clearance therapy'],"['Anti-Allergic Agents', 'Antidepressive Agents', 'Antihistamines for Systemic Use', 'Antipruritics', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Propylamine Derivatives', 'Pyridines', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Substituted Alkylamines']" +DB00833,Cefaclor,Cefacloris a second generation cephalosporin used to treat a wide variety of infections in the body.,"['Q75Y35', 'Q8XJ01']","Cefaclor is a second generation cephalosporin antibiotic with a spectrum resembling first-generation cephalosporins.In vitrotests demonstrate that the bactericidal action of the cephalosporins results from inhibition of cell-wall synthesis. As indicated byin vitroandin vivoclinical studies, cefaclor was shown to be effective against most strains of Gram positive aerobes - Staphylococci (including coagulase-positive, coagulase-negative, and penicillinase-producing strains),Streptococcus pneumoniae,Streptococcus pyogenes(group A ß-hemolytic streptococci), as well as Gram-negative aerobes -Escherichia coli,Haemophilus influenzae(including ß-lactamase-producing ampicillin-resistant strains),Klebsiella sp, andProteus mirabilis.",[H][C@]12SCC(Cl)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(O)=O,"Cefaclor, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that cefaclor interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'BSEP/ABCB11 Substrates', 'Cephalosporins', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB00565,Cisatracurium,"Cisatracuriumis a skeletal muscle relaxant used to facilitate tracheal intubation, muscle relaxation in surgery, or mechanical ventilation.","['Q9GZZ6', 'Q15822', 'P32297', 'P43681', 'P30532', 'Q15825', 'P36544', 'Q9UGM1', 'P17787', 'Q05901', 'P30926', 'P02708', 'P08172']","The dose required to produce 95% suppression of twitch response to nerve stimulation (ED95) of cisatracurium is 0.05 mg/kg in adults receiving opioid/nitrous oxide/oxygen anesthesia.3,5The degree and duration of the neuromuscular block produced by cisatracurium increases in a dose-dependent manner, while the time to maximum neuromuscular block decreases.3Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action.2Cisatracurium acts on cholinergic receptors, blocking neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine.1The use of cisatracurium may lead to residual paralysis, as well as a higher risk of seizure. Medication errors increase the risk of death, and the use of certain drugs may potentiate the neuromuscular blocking action of cisatracurium.5",COC1=CC2=C(C=C1OC)[C@@H](CC1=CC(OC)=C(OC)C=C1)[N@@+](C)(CCC(=O)OCCCCCOC(=O)CC[N@@+]1(C)CCC3=C(C=C(OC)C(OC)=C3)[C@H]1CC1=CC(OC)=C(OC)C=C1)CC2,"Like other non-depolarising neuromuscular blocking agents, cisatracurium binds competitively to cholinergic receptors in motor end-plate neurons, blocking acetylcholine from accessing the receptors.Therefore, in the presence of cisatracurium, an end-plate potential cannot be developed. Ion channels remain closed, the cell does not depolarize, and an action potential is not transmitted.TargetActionsOrganismANeuronal Acetylcholine (nACh) Receptor SubunitsantagonistHumansUAcetylcholine receptor subunit alphaantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans","['General Anesthesia', 'Skeletal muscle relaxation for mechanical ventilation', 'Smooth muscle relaxation prior to radiological procedures therapy']","['Anticholinergic Agents', 'Benzylisoquinolines', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular Nondepolarizing Blockade', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Nicotinic Antagonists', 'Peripheral Nervous System Agents']" +DB06151,Acetylcysteine,Acetylcysteineis a medication that can be used as a mucolytic in patients with certain lung conditions and as an antidote for acetaminophen overdose.,"['P48637', 'Q9UPY5', 'Q03154', 'O14920', 'O15111', 'Q13224', 'Q05586', 'Q12879', 'O15399', 'Q8TCU5']","Acetylcysteine is indicated for mucolytic therapy and in the management of acetaminophen overdose.14,15,16,17It has a short duration of action as it is given every 1-8 hours depending on route of administration, and has a wide therapeutic window.14,15,16,17Patients should be counselled regarding diluting oral solutions in cola for taste masking,7the risk of hypersensitivity, and the risk of upper gastrointestinal hemorrhage.14,15,16,17",CC(=O)N[C@@H](CS)C(O)=O,"A number of possible mechanisms for the mucolytic activity of acetylcysteine have been proposed. Acetylcysteine's sulfhydryl groups may hydrolize disulfide bonds within mucin, breaking down the oligomers, and making the mucin less viscous.,Acetylcysteine has also been shown to reduce mucin secretion in rat models.It is an antioxidant in its own right but is also deacetylated to cysteine, which participates in the synthesis of the antioxidant glutathione.The antioxidant activity may also alter intracellular redox reactions, decreasing phosphorylation of EGFR and MAPK, which decrease transcription of the gene MUCAC which produces mucin.In the case of acetaminophen overdoses, a portion of the drug is metabolized by CYPE to form the potentially toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).The amount of NAPQI produced in an overdose saturates and depletes glutathione stores.The free NAPQI promiscuously binds to proteins in hepatocytes, leading to cellular necrosis.Acetylcysteine can directly conjugate NAPQI or provide cysteine for glutathione production and NAPQI conjugation.TargetActionsOrganismAGlutathione synthetasestimulatorHumansACystine/glutamate transporteractivatorHumansUNAPQI (N-acetyl-p-benzoquinone imine)reducerHumansUAminoacylase-substrateHumansUInhibitor of nuclear factor kappa-B kinase subunit betainhibitorHumansUInhibitor of nuclear factor kappa-B kinase subunit alphainhibitorHumansUGlutamate receptor ionotropic, NMDA BactivatorHumansUGlutamate receptor ionotropic, NMDA activatorHumansUGlutamate receptor ionotropic, NMDA AactivatorHumansUGlutamate receptor ionotropic, NMDA DactivatorHumansUGlutamate receptor ionotropic, NMDA AactivatorHumans",['Airway secretion clearance therapy'],"['Amino Acids', 'Amino Acids, Neutral', 'Amino Acids, Peptides, and Proteins', 'Amino Acids, Sulfur', 'Antidote for Acetaminophen Overdose', 'Antidotes', 'Antioxidants', 'Compounds used in a research, industrial, or household setting', 'Cough and Cold Preparations', 'Cysteine', 'Decreased Respiratory Secretion Viscosity', 'Expectorants', 'Free Radical Scavengers', 'Increased Glutathione Concentration', 'OATP1B1/SLCO1B1 Inhibitors', 'Ophthalmologicals', 'Protective Agents', 'Reduction Activity', 'Respiratory System Agents', 'Sensory Organs', 'Sulfhydryl Compounds', 'Sulfur Compounds']" +DB01339,Vecuronium,Vecuroniumis a nondepolarizing neuromuscular blocking agent used to relax muscles or as an adjunct in general anesthesia during surgical procedures.,['Q15822'],The principal pharmacologic effects demonstrated by vecuronium revolve around its competitive binding of cholinergic receptors located at motor end plates. This competitive binding results in muscle relaxant effects that are typically employed as an adjunct to general anesthesia.,[H][C@@]12C[C@@H]([C@H](OC(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@H](OC(C)=O)[C@H](C[C@]12C)N1CCCCC1)[N+]1(C)CCCCC1,"Vecuronium is a bisquaternary nitrogen compound that acts by competitively binding to nicotinic cholinergic receptors. The binding of vecuronium decreases the opportunity for acetylcholine to bind to the nicotinic receptor at the postjunctional membrane of the myoneural junction. As a result, depolarization is prevented, calcium ions are not released and muscle contraction does not occur.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumans","['General Anesthesia', 'Facilitation of small bowel intubation therapy', 'Smooth muscle relaxation prior to radiological procedures therapy']","['Androstanes', 'Androstanols', 'Anticholinergic Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Fused-Ring Compounds', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular Nondepolarizing Blockade', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Steroids']" +DB00200,Hydroxocobalamin,Hydroxocobalaminis a synthetic form of vitamin B12 used to treat vitamin B12 associated disorders and cyanide poisoning.,"['Q99707', 'P22033', 'Q8IVH4', 'P20061', 'Q9BXJ7', 'O60494', 'Q9Y4U1']","Hydroxocobalamin is a synthetic, injectable form of Vitamin B12. Hydroxocobalamin is actually a precursor of two cofactors or vitamins (Vitamin B12 and Methylcobalamin) which are involved in various biological systems in man. Vitamin B12 is required for the conversion of methylmalonate to succinate. Deficiency of this enzyme could therefore interfere with the production of lipoprotein in myelin sheath tissue and so give rise to neurological lesions. The second cofactor, Methylcobalamin, is necessary for the conversion of homocysteine to methionine which is essential for the metabolism of folic acid. Deficiency of tetrahydrafolate leads to reduced synthesis of thymidylate resulting in reduced synthesis of DNA which is essential for cell maturation. Vitamin B12 is also concerned in the maintenance of sulphydryl groups in reduced form, deficiency leading to decreased amounts of reduced SH content of erythrocytes and liver cells. Overall, vitamin B12 acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. It is necessary for growth, cell replication, hematopoiesis, and nucleoprotein as well as myelin synthesis. This is largely due to its effects on metabolism of methionine folic acid, and malonic acid.",[N+]1=2[Co-3]345([N+]6=C7[C@H]([C@@](CC(=O)N)(C)[C@@]6([C@@]6(N3C(=C(C)C3=[N+]4C(C(C)(C)[C@@H]3CCC(=O)N)=CC3=[N+]5C(=C7C)[C@@](CC(=O)N)([C@@H]3CCC(=O)N)C)[C@@](C)([C@H]6CC(=O)N)CCC(NC[C@@H](C)OP(=O)(O[C@@H]3[C@H](O[C@H](N(C4=CC(=C(C=C14)C)C)C=2)[C@@H]3O)CO)[O-])=O)[H])C)CCC(=O)N)O[H],"Vitamin B exists in four major forms referred to collectively as cobalamins; deoxyadenosylcobalamin, methylcobalamin, hydroxocobalamin, and cyanocobalamin. Two of these, methylcobalamin and -deoxyadenosyl cobalamin, are primarily used by the body. Methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine. Methionine in turn is required for DNA methylation. -Deoxyadenosyl cobalamin is a cofactor needed by the enzyme that converts L-methylmalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of energy from proteins and fats. Furthermore, succinyl CoA is necessary for the production of hemoglobin, the substances that carries oxygen in red blood cells.TargetActionsOrganismAMethionine synthasecofactorHumansAMethylmalonyl-CoA mutase, mitochondrialcofactorHumansUMethylmalonic aciduria type A protein, mitochondrialother/unknownHumansUTranscobalamin-otherHumansUProtein amnionlessotherHumansUCubilinotherHumansUMethylmalonic aciduria and homocystinuria type C proteinother/unknownHumans",[],"['Antianemic Preparations', 'Antidotes', 'Blood and Blood Forming Organs', 'Corrinoids', 'Drugs that are Mainly Renally Excreted', 'Hematinics', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Micronutrients', 'Nutritional Support', 'Vitamin B Complex', 'Vitamin B12 and Folic Acid', 'Vitamins']" +DB01284,Tetracosactide,Tetracosactideis a diagnostic agent used in the screening of patients presumed to have adrenocortical insufficiency.,['Q01718'],"Cosyntropin exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N- terminal portion of the molecule and that the 1-20 amino acid residue is the minimal sequence retaining full activity. Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residue. For example, the decrement from 20 to 19 results in a 70% loss of potency. The pharmacologic profile of Cosyntropin is similar to that of purified natural ACTH. It has been established that 0.25 mg of Cosyntropin will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. Cosyntropin has less immunogenic activity than ACTH because the amino acid sequence having most of the antigenic activity of ACTH, i.e., amino acids 25-39, is not present in cosyntropin. The extra-adrenal effects which natural ACTH and Cosyntropin have in common include increased melanotropic activity, increased growth hormone secretion and an adipokinetic effect. These are considered to be without physiological or clinical significance.",CSCC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(O)=O,"Cosyntropin combines with a specific receptor in the adrenal cell plasma membrane and, in patients with normal adrenocortical function, stimulates the initial reaction involved in the synthesis of adrenal steroids (including cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol by increasing the quantity of the substrate within the mitochondria. Cosyntropin does not significantly increase plasma cortisol concentration in patients with primary or secondary adrenocortical insufficiency.TargetActionsOrganismAAdrenocorticotropic hormone receptoragonistHumans",[],"['Adrenals', 'Adrenocortical Insufficiency', 'Adrenocorticotropic Hormone', 'Amino Acids, Peptides, and Proteins', 'Anterior Pituitary Lobe Hormones and Analogues', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Melanocortins', 'Nerve Tissue Proteins', 'Neuropeptides', 'Peptide Hormones', 'Peptides', 'Pituitary', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormones', 'Pituitary Hormones, Anterior', 'Pro-Opiomelanocortin', 'Proteins', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB01337,Pancuronium,Pancuroniumis a neuromuscular blocker used as an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.,"['Q15822', 'P08172', 'P20309']","Pancuronium is a non-depolarising muscle relaxant similar to curare. It acts as a competitive acetylcholine antagonist on neuromuscular junctions, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptors. It is, unlike suxamethonium, a non-depolarising agent, which means, that it causes no spontaneous depolarisations upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculations upon administration. Pancuronium has no hormonal activity. It exerts slight vagolytic activity (i.e. diminishing activity of the vagus nerve) and no ganglioplegic (i.e., blocking ganglions) activity.",[H][C@@]12C[C@@H]([C@H](OC(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@H](OC(C)=O)[C@H](C[C@]12C)[N+]1(C)CCCCC1)[N+]1(C)CCCCC1,"Nondepolarizing neuromuscular blocking agents inhibit neuromuscular transmission by competing with acetylcholine for the cholinergic receptors of the motor end plate, thereby reducing the response of the end plate to acetylcholine. This type of neuromuscular block is usually antagonized by anticholinesterase agents.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans","['General Anesthesia', 'Facilitation of small bowel intubation therapy', 'Smooth muscle relaxation prior to radiological procedures therapy']","['Agents producing tachycardia', 'Androstanes', 'Androstanols', 'Anticholinergic Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Fused-Ring Compounds', 'Muscarinic Antagonists', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular Nondepolarizing Blockade', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'OCT1 inhibitors', 'OCT1 substrates', 'Peripheral Nervous System Agents', 'Steroids']" +DB00483,Gallamine triethiodide,Gallamine triethiodideis a nondepolarizing nerve blocker used in addition to anesthesia to cause skeletal muscle relaxation.,"['P08172', 'P22303', 'Q15822', 'P11229', 'P08912']","Gallamine Triethiodide is a nondepolarizing neuromuscular blocking drug (NDMRD) used as an adjunct to anesthesia to induce skeletal muscle relaxation. The actions of gallamine triethiodide are similar to those of tubocurarine, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. Muscle groups differ in their sensitivity to these types of relaxants with ocular muscles (controlling eyelids) being most sensitive, followed by the muscles of the neck, jaw, limbs and then abdomen. The diaphragm is the least sensitive muscle to NDMRDs. Although the nondepolarizing neuromuscular blocking drugs do not have the same adverse effects as succinylcholine, their onset of action is slower. They also have a longer duration of action, making them more suitable for maintaining neuromuscular relaxation during major surgical procedures.",[I-].[I-].[I-].CC[N+](CC)(CC)CCOC1=CC=CC(OCC[N+](CC)(CC)CC)=C1OCC[N+](CC)(CC)CC,It competes with acetylcholine (ACh) molecules and binds to muscarinic acetylcholine receptors on the post-synaptic membrane of the motor endplate. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. It blocks the action of ACh and prevents activation of the muscle contraction process. It can also act on nicotinic presynaptic acetylcholine receptors which inhibits the release of ACh.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAAcetylcholinesteraseinhibitorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUMuscarinic acetylcholine receptor MNot AvailableHumansUMuscarinic acetylcholine receptor MNot AvailableHumans,[],"['Agents producing tachycardia', 'Amines', 'Anticholinergic Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Muscarinic Antagonists', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Onium Compounds', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds']" +DB00372,Thiethylperazine,Thiethylperazineis a drug used for the treatment of nausea and vomiting.,['P14416'],"Thiethylperazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, Thiethylperazine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.",CCSC1=CC2=C(SC3=CC=CC=C3N2CCCN2CCN(C)CC2)C=C1,"Thiethylperazine is an antagonist at types , , and dopamine receptors, -HT receptor types A and C, muscarinic receptors through , alpha()-receptors, and histamine H-receptors. Thiethylperazine's antipsychotic effect is due to antagonism at dopamine and serotonin type receptors, with greater activity at serotonin -HT receptors than at dopamine type- receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H-receptors, and alpha()-receptors also occurs with thiethylperazine.TargetActionsOrganismUDopamine D receptorantagonistHumans",[],"['Antiemetics', 'Antihistamines for Systemic Use', 'Antipsychotic Agents', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenothiazine Derivatives', 'Phenothiazines', 'Piperazines', 'Sulfur Compounds']" +DB00768,Olopatadine,Olopatadineis a histamine H1 antagonist used to treat allergic conjunctivitis and rhinitis.,"['P35367', 'P25021', 'Q9Y5N1', 'P23297', 'P80511', 'P04271', 'Q99584', 'P29034']","Inflammatory reactions in response to various stimuli are mediated by endogenous mediators and other pro-inflammatory factors. Histamine receptor activation and mast cell degranulation are primary mechanisms that cause inflammatory reactions such as ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis.3Olopatadine is an anti-allergenic molecule and mast cell stabilizer that inhibits thein vivotype 1 immediate hypersensitivity reaction.10By blocking the effects of histamine, olopatadine works to reduce the symptoms of allergies and inflammation at various sites of administration, including the eyes and nose. It has shown to exert antihistaminic effects in isolated tissues, animal models, and humans.8Olopatadine also demonstrated dose-dependent inhibition of immunologically-stimulated release of histamine from rat basophilic leukemia cells and human conjunctival mast cellsin vitro.3Olopatadine has a relatively rapid onset of action and prolonged duration, where it was shown to mediate anti-histaminic effects at 5 minutes to 24 hours post-administration.3While olopatadine is a non-sedating antihistamine agent, there have been reports of somnolence in some patients taking nasal olopatadine during clinical trials.8Temporary blurred vision or other visual disturbances were observed following ophthalmic administration. Olopatadine has negligible effects on alpha-adrenergic, dopamine, muscarinic type 1 and 2, and serotonin receptors.10In clinical trials, there was no evidence of any effect of olopatadine on QT prolongation was observed following intranasal administration.8",CN(C)CC\C=C1\C2=CC=CC=C2COC2=C1C=C(CC(O)=O)C=C2,"Histamine is a biogenic vasoactive amine that binds to its receptors, which are G-protein coupled receptors. Signaling through the histamine H receptor is thought to primarily promote the activation of inflammatory reactions, such as allergy, asthma, and autoimmune diseases.H receptor signaling activates the intracellular transcription factors, such as IP, PLC, PKC, DAG, and intracellular calcium ions, which all work to activate further downstream cascades. Activated downstream cascades lead to the production of cytokines, the release of mast cell inflammatory mediators, synthesis of prostacyclins, activation of platelet factor, as well as the synthesis of nitric oxide, arachidonic acid, and thromboxane, which all contribute to inflammatory reactions.Olopatadine is an anti-allergic molecule that works via several mechanisms. As a mast cell stabilizer, it stabilizes rodent basophils and human conjunctival mast cells and inhibits the immunologically-stimulated release of histamine.Olopatadine acts as an antagonist at the histamine H receptors with high selectivity, which is explained by a unique receptor binding pocket that consists of the aspartate residue in the third transmembrane helix and other sites in the H receptor.Upon binding, olopatadine blocks the H receptor signaling pathway, inhibiting the release of inflammatory mediators, such as tryptase, prostaglandin D, TNF-alpha, as well as pro-inflammatory cytokines.It also decreases chemotaxis and inhibits eosinophil activation.In vitro, olopatadine was shown to inhibit epithelial cell intercellular adhesion molecule- (ICAM-), which promotes the recruitment of migrating pro-inflammatory mediators.TargetActionsOrganismAHistamine H receptorantagonistHumansUHistamine H receptorantagonistHumansUHistamine H receptorantagonistHumansUProtein S-AantagonistHumansUProtein S-AantagonistHumansUProtein S-Bother/unknownHumansUProtein S-Aother/unknownHumansUProtein S-AantagonistHumans",[],"['Anti-Allergic Agents', 'Anti-Inflammatory Agents', 'Antiallergic Agents, Excl. Corticosteroids', 'Antihistamine Drugs', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Decongestants and Antiallergics', 'Decreased Histamine Release', 'Dibenzoxepins', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Histamine H1 Inhibitors', 'Mast Cell Stabilizers', 'Nasal Preparations', 'Neurotransmitter Agents', 'Ophthalmologicals', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Sensory Organs', 'Sensory System Agents']" +DB00728,Rocuronium,Rocuroniumis a vecuronium analog used to facilitate tracheal intubation and to relax skeletal muscles during surgery.,"['Q15822', 'P08172', 'P46098']","Neuromuscular blocking agents are drugs that cause skeletal muscle relaxation primarily by causing a decreased response to the neurotransmitter acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle. At that site, ACh normally produces electrical depolarization of the postjunctional membrane of motor end-plate, which leads to conduction of muscle action potential and subsequently induces skeletal muscle contraction. Neuromuscular agents are classified as depolarizing or nondepolarizing. Rocuronium is a nondepolarizing neuromuscular blocking agent with a rapid to intermediate onset depending on dose and intermediate duration. Rocuronium, like vecuronium is longer acting in infants than in children. However, unlike vecuronium, rocuronium retains the characteristics of an intermediate-acting NMBD in infants.",[H][C@@]12C[C@@H]([C@H](OC(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@H](O)[C@H](C[C@]12C)N1CCOCC1)[N+]1(CC=C)CCCC1,"Rocuronium acts by competing for cholinergic receptors at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium. Rocuronium acts by competitively binding to nicotinic cholinergic receptors. The binding of vecuronium decreases the opportunity for acetylcholine to bind to the nicotinic receptor at the postjunctional membrane of the myoneural junction. As a result, depolarization is prevented, calcium ions are not released and muscle contraction does not occur. Evidence also suggests that nondepolarizing agents can affect ACh release. It has been hypothesized that nondepolarzing agents bind to postjunctional (""curare"") receptors and may therefore interfere with the sodium and potassium flux, which is responsible for depolarization and repolarization of the membranes involved in muscle contraction.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansU-hydroxytryptamine receptor AantagonistHumans","['Curarization therapy', 'Neuromuscular blocking therapy', 'Facilitation of small bowel intubation therapy']","['Agents producing tachycardia', 'Androstanes', 'Androstanols', 'Anticholinergic Agents', 'Central Nervous System Depressants', 'Fused-Ring Compounds', 'Muscarinic Antagonists', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular Nondepolarizing Blockade', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Nicotinic Antagonists', 'OCT1 inhibitors', 'OCT1 substrates', 'Peripheral Nervous System Agents', 'Steroids']" +DB01060,Amoxicillin,"Amoxicillinis a penicillin derivative used for the treatment of infections caused by gram-positive bacteria, in particular streptococcal bacteria causing upper respiratory tract infections.",['Q8L103'],"Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis.9,10,5Amoxicillin has a long duration of action as it is usually given twice daily.15Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity.14Patients should be counselled regarding the risk of anaphylaxis,Clostridium difficileinfections, and bacterial resistance.17",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O,"Amoxicillin competitively inhibits penicillin-binding protein and other high molecular weight penicillin binding proteins.,Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls.Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action.,TargetActionsOrganismUPenicillin binding proteininhibitorHelicobacter pylori",[],"['Alimentary Tract and Metabolism', 'Amides', 'Aminopenicillins', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 inhibitors', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00732,Atracurium besylate,Atracurium besylateis a non-depolarizing neuromuscular blocker used to facilitate endotracheal intubation and relax skeletal muscles during surgery.,['Q15822'],"Atracurium is a nondepolarizing skeletal muscle relaxant. Atracurium can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. The duration of neuromuscular block produced by Atracurium is approximately one third to one half the duration of block by d-tubocurarine, metocurine, and pancuronium at initially equipotent doses. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of Atracurium. Repeated administration of maintenance doses of Atracurium has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results.",[O-]S(=O)(=O)C1=CC=CC=C1.[O-]S(=O)(=O)C1=CC=CC=C1.COC1=CC2=C(C=C1OC)C(CC1=CC(OC)=C(OC)C=C1)[N+](C)(CCC(=O)OCCCCCOC(=O)CC[N+]1(C)CCC3=C(C=C(OC)C(OC)=C3)C1CC1=CC(OC)=C(OC)C=C1)CC2,"Atracurium antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumans","['Neuromuscular blocking therapy', 'Facilitation of small bowel intubation therapy']","['Anticholinergic Agents', 'Benzylisoquinolines', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Miscellaneous Skeletal Muscle Relaxants', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Peripheral Nervous System Agents']" +DB11136,Chromium,Chromiumis an ingredient found in a variety of supplements and vitamins.,['P00167'],"Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiencyLabel.",[Cr],"Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Its role in potentiating insulin signalling cascades has been implicated in several studies. Chromium upregulates insulin-stimulated insulin signal transduction via affecting effector molecules downstream of the insulin receptor (IR). IR-mediated signalling pathway involves phoshorylation of multiple intracellular domains and protein kinases, and downstream effector molecules. Upon activation by ligands, intracellular β-subunit of IR autophosphorylates and activates tyrosine kinase domain of the IR, followed by activation and phosphorylation of regulatory proteins and downstream signalling effectors including phosphatidylinositol -kinase (PIK). PIK activates further downstream reaction cascades to activate protein kinase B (Akt) to ultimately promote translocation of glucose transporter- (Glut)-vesicles from the cytoplasm to the cell surface and regulate glucose uptake. Chromium enhances the kinase activity of insulin receptor β and increases the activity of downstream effectors, pI-kinase and Akt.Under insulin-resistant conditions, chromium also promotes GLUT- transporter translocation that is independent of activity of IR, IRS-, PI-kinase, or Akt; chromium mediates cholesterol efflux from the membranes via increasing fluidity of the membrane by decreasing the membrane cholesterol and upregulation of sterol regulatory element-binding protein. As a result, intracellular GLUT- transporters are stimulated to translocate from intracellular to the plasma membrane, leading to enhanced glucose uptake in muscle cells. Chromium attenuates the activity of PTP-Bin vitro,which is a negative regulator of insulin signaling. It also alleviates ER stress that is observed to be elevated the suppression of insulin signaling. ER stress is thought to activate c-Jun N-terminal kinase (JNK), which subsequently induces serine phosphorylation of IRS and aberration of insulin signalling. Transient upregulation of AMPK by chromium also leads to increased glucose uptake.TargetActionsOrganismUCytochrome bsubstrateHumans",['Mineral supplementation therapy'],"['Cell-mediated Immunity', 'Diet, Food, and Nutrition', 'Drugs that are Mainly Renally Excreted', 'Elements', 'Food', 'Increased Histamine Release', 'Metals', 'Metals, Heavy', 'Micronutrients', 'Minerals', 'Physiological Phenomena', 'Standardized Chemical Allergen', 'Trace Elements', 'Transition Elements']" +DB01128,Bicalutamide,Bicalutamideis an androgen receptor inhibitor used to treat Stage D2 metastatic carcinoma of the prostate.,['P10275'],"Bicalutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Bicalutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Bicalutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration.",CC(O)(CS(=O)(=O)C1=CC=C(F)C=C1)C(=O)NC1=CC(=C(C=C1)C#N)C(F)(F)F,"Bicalutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin which stimulate the growth of normal and malignant prostatic tissue.TargetActionsOrganismAAndrogen receptorantagonistHumans",[],"['Amides', 'Amines', 'Androgen Receptor Antagonists', 'Androgen Receptor Inhibitors', 'Aniline Compounds', 'Antiandrogens', 'Antiandrogens, non-steroidal', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Benzene Derivatives', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'Sulfones', 'Sulfur Compounds']" +DB07565,Chloramphenicol succinate,Chloramphenicol succinateis a broad-spectrum antibiotic agent used for the treatment of acute and severe infections caused by susceptible bacterial strains.,['P24093'],"Chloramphenicol succinate is a prodrug of chloramphenicol, which binds to bacterial ribosomes and prevents translation.1,6,7It has a narrow therapeutic index8and a moderate duration of action.10Patients should be counselled regarding the risk of serious fatal blood dyscrasias.10",O[C@@H]([C@@H](COC(=O)CCC(O)=O)NC(=O)C(Cl)Cl)C1=CC=C(C=C1)[N+]([O-])=O,"Chloramphenicol succinate is hydrolyzed into the active chloramphenicol.Chloramphenicol resembles uridine-'-phosphate.It binds to the residues A and A in the S rRNA of the S ribosomal subunit ofE. coli, which prevents translation.TargetActionsOrganismUDr hemagglutinin structural subunitinhibitorEscherichia coli",[],"['Alcohols', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Benzene Derivatives', 'Glycols', 'Narrow Therapeutic Index Drugs', 'Nitro Compounds', 'Nitrobenzenes', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Propylene Glycols']" +DB00188,Bortezomib,Bortezomibis a proteasome inhibitor used to treat multiple myeloma in patients who have not been successfully treated with at least two previous therapies.,"['P28074', 'P20618']","Bortezomib works to target the ubiquitin-proteasome pathway, an essential molecular pathway that regulates intracellular concentrations of proteins and promotes protein degradation.1The ubiquitin-proteasome pathway is often dysregulated in pathological conditions, leading to aberrant pathway signalling and the formation of malignant cells. In one study, patient-derived chronic lymphocytic leukemia (CLL) cells contained 3-fold higher levels of chymotrypsin-like proteasome activity than normal lymphocytes.1By reversibly inhibiting proteasome, bortezomib prevents proteasome-mediated proteolysis. Bortezomib exerts a cytotoxic effect on various cancer cell typesin vitroand delays tumour growthin vivoin nonclinical tumour models.7Bortezomib inhibits the proteasome activity in a dose-dependent manner. In one pharmacodynamic study, more than 75% of proteasome inhibition was observed in whole blood samples within one hour after dosing of bortezomib.4",CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C1=CN=CC=N1)B(O)O,"The ubiquitin-proteasome pathway is a homeostatic proteolytic pathway for intracellular protein degradation: proteins marked with a poly-ubiquitin chain are degraded to small peptides and free ubiquitin by the proteasome, which is a large multimeric protease.Aberrant proteasome-dependent proteolysis, as seen in some malignancies, can lead to uncontrolled cell division, leading to tumorigenesis, cancer growth, and spread.,Bortezomib is a reversible inhibitor of the S proteasome, which is made up of a S core complexed with a S regulatory complex. Individual β-subunits allow specific catalytic action of the S core.,In mammalian cells, bortezomib is a potent inhibitor of the proteasome’s chymotryptic-like activity, which is attributed to the β-subunit of the S core particle.Bortezomib binds to the active site of the threonine hydroxyl group in the β-subunit.A probing study showed bortezomib also binding to and inhibiting the β-subunit, which mediates the caspase-like activity of the proteasome, and βi-subunit, which is an altered subunit that is expressed to form immunoproteasomes in response to cell stress or inflammation.By inhibiting the proteasome-mediated degradation of key proteins that promote cell apoptosis,bortezomib induces a cell cycle arrest during the G-M phase.It is believed that multiple mechanisms, other than proteasome inhibition, may be involved in the anticancer activity of bortezomib.The anticancer activity of bortezomib was largely associated with suppression of the NF-κB signalling pathway, resulting in the downregulation of anti-apoptotic target genes and expression of anti-apoptic proteins. This may be explained by bortezomib preventing uncontrolled degradation of IκB, which is an inhibitory protein of NF-κB. NOXA, which is a pro-apoptotic factor, induced by bortezomib selectively in cancer cells; thus, it is suggested to be another key mechanism of bortezomib.TargetActionsOrganismAProteasome subunit beta type-inhibitorHumansAProteasome subunit beta type-inhibitorHumans",[],"['Acids', 'Acids, Noncarboxylic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Boron Compounds', 'Boronic Acids', 'Cardiotoxic antineoplastic agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hepatotoxic Agents', 'Hypotensive Agents', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B3 inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Potential QTc-Prolonging Agents', 'Proteasome Inhibitors', 'Pyrazines', 'QTc Prolonging Agents']" +DB00643,Mebendazole,Mebendazoleis a benzimidazole anthelmintic used to treat helminth infections.,"['Q71U36', 'P68371']",Mebendazole is a (synthetic) broad-spectrum anthelmintic. The principal mode of action for Mebendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.,COC(=O)NC1=NC2=C(N1)C=C(C=C2)C(=O)C1=CC=CC=C1,"Mebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies.TargetActionsOrganismATubulin alpha-A chaininhibitorHumansATubulin beta-B chaininhibitorHumans",[],"['Acids, Acyclic', 'Anthelmintics', 'Anti-Infective Agents', 'Antihelminthic', 'Antimitotic Agents', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Benzimidazole Derivatives', 'Benzimidazoles', 'Carbamates', 'Heterocyclic Compounds, Fused-Ring', 'Mitosis Modulators', 'Tubulin Modulators']" +DB01254,Dasatinib,Dasatinibis a tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia.,"['P00519', 'P12931', 'P29317', 'P06239', 'P07947', 'P10721', 'P09619', 'P51692', 'P42684', 'P06241', 'Q06187', 'Q92570', 'P11274', 'P41240', 'P54756', 'P54760', 'P09769', 'P42685', 'P11142', 'P07948', 'Q9NYL2', 'Q16539', 'Q06203']","Dasatinib is an orally available small-molecule multikinase inhibitor.5During clinical trials, less than 1% of patients treated with dasatinib had QTc prolongation as an adverse reaction, and 1% experienced a QTcF higher than 500 ms. The use of dasatinib is also associated with myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, pulmonary arterial hypertension, severe dermatologic reactions, tumor lysis syndrome and hepatotoxicity. It may also cause embryo-fetal toxicity and lead to adverse reactions associated with bone growth and development in pediatric patients.7",CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1,"Dasatinib is a tyrosine kinase inhibitor with several targets. At nanomolar concentrations, it inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA, and PDGFRβ.,,In patients with chronic myeloid leukemia (CML), the tyrosine kinase activity of BCR-ABL is deregulated, leading to the growth, proliferation and survival of cancerous hematopoietic cells. Dasatinib binds to the active and inactive conformation of the ABL kinase domain with a higher affinity than imatinib.In chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL, dasatinib inhibits cell growth. Also, dasatinib hasin vitroactivity against leukemic cell lines that are either sensitive or resistant to imatinib.It has been suggested that dasatinib is able to overcome imatinib resistance caused by BCR-ABL kinase domain mutations because it does not require interaction with some of the residues involved in those mutations.,TargetActionsOrganismATyrosine-protein kinase ABLinhibitormultitargetHumansAProto-oncogene tyrosine-protein kinase SrcinhibitormultitargetHumansAEphrin type-A receptor antagonistHumansATyrosine-protein kinase LckinhibitormultitargetHumansATyrosine-protein kinase YesinhibitorHumansAMast/stem cell growth factor receptor KitantagonistHumansAPlatelet-derived growth factor receptor betaantagonistHumansUSignal transducer and activator of transcription BinhibitorHumansUTyrosine-protein kinase ABLmultitargetHumansATyrosine-protein kinase FyninhibitormultitargetHumansUTyrosine-protein kinase BTKinhibitorHumansUNuclear receptor subfamily group A member inhibitorHumansABreakpoint cluster region proteininhibitorHumansUTyrosine-protein kinase CSKinhibitorHumansUEphrin type-A receptor inhibitorHumansUEphrin type-B receptor inhibitorHumansUTyrosine-protein kinase FgrinhibitorHumansUTyrosine-protein kinase FRKbinderHumansUHeat shock cognate kDa proteinbinderHumansUTyrosine-protein kinase LyninhibitorHumansUMitogen-activated protein kinase kinase kinase MLTbinderHumansUMitogen-activated protein kinase binderHumansUAmidophosphoribosyltransferasebinderHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Bcr-Abl Tyrosine Kinase Inhibitors', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Protein Kinase Inhibitors', 'Pyrimidines', 'QTc Prolonging Agents', 'Sulfur Compounds', 'Thiazoles', 'Tyrosine Kinase Inhibitors']" +DB00127,Spermine,"Spermine is a spermidine-derived biogenic polyamine found as a polycation at all pH values. Found in various tissues and organisms, it often acts as an essential growth factor in some bacterial species. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure.","['P52788', 'Q9NWM0', 'P11926', 'P41180', 'P08588', 'P07550']",Spermine is a polyamine. It is an organic molecule that is involved in cellular metabolism.,NCCCNCCCCNCCCN,"Spermine is derived from spermidine by spermine synthase. Spermine is a polyamine, a small organic cations that is absolutely required for eukaryotic cell growth. Spermine, is normally found in millimolar concentrations in the nucleus. Spermine functions directly as a free radical scavenger, and forms a variety of adducts that prevent oxidative damage to DNA. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. Hence, spermine is a major natural intracellular compound capable of protecting DNA from free radical attack. Spermine is also implicated in the regulation of gene expression, the stabilization of chromatin, and the prevention of endonuclease-mediated DNA fragmentation.TargetActionsOrganismASpermine synthaseligandHumansASpermine oxidaseligandHumansADNAbinderHumansUOrnithine decarboxylaseproduct ofHumansUExtracellular calcium-sensing receptorNot AvailableHumansUBeta- adrenergic receptorNot AvailableHumansUBeta- adrenergic receptorNot AvailableHumans",[],"['Amines', 'Biogenic Amines', 'Biogenic Polyamines', 'Dietary Supplements', 'OCT1 substrates', 'Polyamines', 'Supplements']" +DB00318,Codeine,Codeineis an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.,"['P35372', 'P41145', 'P41143']","General effectsCodeine is a weak narcotic pain reliever and cough suppressant that is similar to morphine and hydrocodone. A small amount of ingested codeine is converted to morphine in the body. Codeine increases tolerance to pain, reducing existing discomfort. In addition to decreasing pain, codeine also causes sedation, drowsiness, and respiratory depression4.Antitussive activityThis drug has shown antitussive activity in clinical trials6and has been effective in cough secondary to tuberculosis and insomnia due to coughing4. Codeine suppresses the cough reflex through a direct effect on the cough center in the medulla16.Effects on intestinal motilityCodeine may reduce intestinal motility through both a local and possibly central mechanism of action17. This may possibly lead to constipation16. The chronic use of opioids, including codeine sulfate, may lead to obstructive bowel disease, particularly in patients with underlying disorders of intestinal motilityLabel.Effects on the central nervous systemCodeine phosphate is an opioid analgesic with uses similar to those of morphine, but is much less potent as an analgesic. Its primary site of action is at themuopioid receptors distributed throughout the central nervous system. The sedative activities of codeine are less potent than those of morphine16. Codeine may cause respiratory system depression by the activation of μ-opioid receptors at specific sites in the central nervous system8.Effects on blood pressureThis drug poses an increased risk of compromised ability to maintain blood pressure due to peripheral vasodilation and other mechanismsLabel.Effects on chronic cancer pain and other types of painCodeine is an opioid analgesic with similar indications to those of morphine, however, is much less potent in its pain alleviating properties. Its primary action takes place at the mu opioid receptors, which are distributed throughout the central nervous system. The average duration of action is about 4 hours16.Regular dosing of opioid analgesics such as codeine in patients with severe cancer pain has been well documented to improve symptoms4,7.",[H][C@]12C=C[C@H](O)[C@@H]3OC4=C5C(C[C@H]1N(C)CC[C@@]235)=CC=C4OC,"Although the exact mechanism of action of codeine is still unknown, it is generally thought to be mediated through the agonism of opioid receptors, particularly the mu-opioid receptors.Morphine was previously postulated to contribute to the analgesic effect of codeine due to the O-demethylation of codeine to morphine by CYPD. Particularly, CYPD poor metabolizer did not experience the analgesic effect of codeine.,However, this is unlikely to be the main mechanism of action of codeine as only % of codeine is metabolized to morphine.Other hypotheses also postulate that codeine--glucuronide, the main metabolite of codeine, mediates the analgesic effect of codeine as it not only has an affinity to the mu receptors as codeine but also can be metabolized to morphine--glucuronide, which was observed to be more potent than morphine.Binding to the mu receptors by codeine activates the G-proteins Gαi, causing a decrease in intracellular cAMP and Ca+level.,This causes hyperpolarization of nociceptive neurons, thus imparing the transmission of pain signals.,TargetActionsOrganismAMu-type opioid receptoragonistregulatorHumansAKappa-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumans",['Airway secretion clearance therapy'],"['Alkaloids', 'Analgesics', 'Antitussive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cough and Cold Preparations', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Natural Opium Alkaloids', 'Nervous System', 'OAT1/SLC22A6 inhibitors', 'OCT1 inhibitors', 'OCT1 substrates', 'Opiate Agonists', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'Opium Alkaloids and Derivatives', 'Phenanthrenes', 'Respiratory System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'UGT2B7 substrates']" +DB00938,Salmeterol,Salmeterolis a long-acting beta-2 adrenergic receptor agonist used to treat asthma and COPD.,"['P07550', 'P08588', 'P13945']","Salmeterol is a long acting beta-2 adrenergic receptor agonist that binds to both the active and exo sites of the beta-2 adrenergic receptor.1Salmeterol has a longer duration of action than other beta-2 agonists likesalbutamol.5Patients should be counselled regarding the risks of long acting beta agonist (LABA) monotherapy, hypokalemia, hypoglycemia, and not to take this drug with another LABA.8,9,10,11,12",OCC1=C(O)C=CC(=C1)C(O)CNCCCCCCOCCCCC1=CC=CC=C1,"Beta- adrenoceptor stimulation causes relaxation of bronchial smooth muscle, bronchodilation, and increased airflow.Salmeterol is hypothesized to bind to sites on the beta- adrenoceptor.The saligenin moiety binds to the active site of the beta- adrenoceptor.The hydrophilic tail of salmeterol binds to leucine residues in the exo-site of the beta- adrenoceptor almost irreversibly, allowing salmeterol to persist in the active site, which is responsible for it's long duration of action.,Another hypothesis is that the lipophilic drug diffuses into lipid bilayer of smooth muscle cells and provides a depot of drug to the cells over a longer period of time.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptorinverse agonistHumansUBeta- adrenergic receptorinverse agonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics, Inhalants', 'Agents Causing Muscle Toxicity', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Ethylamines', 'Long-acting beta-adrenoceptor agonists', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetic (Adrenergic) Agents']" +DB01206,Lomustine,Lomustineis an alkylating agent used as a part of chemotherapeutic regimens for the treatment of primary and metastatic brain tumors as well as refractory or relapsed Hodgkin's disease in addition to surgical and/or radiotherapeutic treatments.,['Q9H169'],Lomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle–phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing.,ClCCN(N=O)C(=O)NC1CCCCC1,"Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins.TargetActionsOrganismADNAcross-linking/alkylationHumansUStathmin-antagonistHumans",[],"['Alkylating Activity', 'Alkylating Drugs', 'Amides', 'Antineoplastic Agents', 'Antineoplastic Agents, Alkylating', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nitroso Compounds', 'Nitrosourea Compounds', 'Nitrosoureas', 'Noxae', 'Toxic Actions']" +DB00750,Prilocaine,Prilocaineis a local anesthetic used in dental procedures.,['Q14524'],"Prilocaine binds to the intracellular surface of sodium channels which blocks the subsequent influx of sodium into the cell. Action potential propagation and never function is, therefore, prevented. This block is reversible and when the drug diffuses away from the cell, sodium channel function is restored and nerve propagation returns.",CCCNC(C)C(=O)NC1=CC=CC=C1C,"Prilocaine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",['Local Anaesthesia therapy'],"['Amides', 'Amines', 'Anesthetics', 'Anesthetics, Local', 'Anilides', 'Aniline Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Local Anesthesia', 'Local Anesthetics (Amide)', 'Methemoglobinemia Associated Agents', 'Nervous System', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB01328,Cefonicid,"A second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.","['P02918', 'P0AD68', 'P02919', 'P24228', 'P0AD65']","Cefonicid is a second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.",[H][C@]12SCC(CSC3=NN=NN3CS(O)(=O)=O)=C(N1C(=O)[C@H]2NC(=O)[C@H](O)C1=CC=CC=C1)C(O)=O,"Cefonicid, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.TargetActionsOrganismAPenicillin-binding protein AinhibitorEscherichia coli (strain K)APeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacBinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB05088,Tetrathiomolybdate,"Tetrathiomolybdate is an oral, small-molecule, anticopper agent that is highly specific for lowering the levels of free copper in serum. COPREXA has completed pivotal clinical trials for the treatment of neurologic Wilson's disease. It is also developed for fibrotic disorders based upon the rationale that the fibrotic disease process is dependent upon the availability of free copper in the body.",['P05067'],Tetrathiomolybdate demonstrated the ability to reduce toxic free copper levels and substantially improve clinical neurologic outcomes in Wilson’s patients. Studies also showed it is capable of specifically inhibiting chronic fibrotic disease processes in the lung.,[S-][Mo]([S-])(=S)=S,"Tetrathiomolybdate has demonstrated the ability to inhibit fibrosis in a number of well established animal models through the sequestration of available copper and inhibition of key fibrotric cytokines, including secreted protein acid rich in cysteine (SPARC), NFkappaB, TGF-beta, FGF-, IL-, IL-, IL-, and connective tissue growth factor (CTGF).TargetActionsOrganismUAmyloid beta A proteinNot AvailableHumans",[],"['Adenosine Triphosphatases, antagonists & inhibitors', 'Angiogenesis Modulating Agents', 'Antineoplastic Agents', 'Chelating Agents', 'Compounds used in a research, industrial, or household setting', 'Elements', 'Enzyme Inhibitors', 'Growth Inhibitors', 'Growth Substances', 'Metals', 'Metals, Heavy', 'Sequestering Agents', 'Transition Elements']" +DB01330,Cefotetan,"Cefotetanis an antibiotic medication used for the prophylaxis and treatment of various bacterial infections, including urinary tract infections, bone and joint infection, and lower respiratory tract infections.",['Q75Y35'],Cefotetan is a semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.,[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@]2(NC(=O)C1SC(S1)=C(C(N)=O)C(O)=O)OC)C(O)=O,The bactericidal action of cefotetan results from inhibition of cell wall synthesis by binding and inhibiting the bacterial penicillin binding proteins which help in the cell wall biosynthesis.TargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniae,['Antibiotic pre-surgical prophylaxis'],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Cephamycins', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Tetrazoles', 'Thiazines']" +DB12783,Benserazide,"Benserazideis a medication used to treat Parkinson's disease, parkinsonism, and restless leg syndrome.",['P20711'],"When used as a therapy for treating Parkinson's disease, levadopa's specific mechanism of action revolves around its metabolism into dopamine in the body3,2. Unfortunately, the resultant increase in the levels of circulating dopamine in the blood and to various extracerebral tissues can result in a number of side effects like nausea, vomiting, or even cardiac arrhythmias that may diminish patient adherence3,2. A decarboxylase inhibitor like benserazide is consequently an effective compound to combine with levadopa as it is incapable of crossing the blood-brain barrier itself and therefore allows levadopa to elicit its primary action in the central nervous system, but will prevent the formation of dopamine from levadopa in extracerebral tissues - thereby acting to minimize the occurrence of extracerebral side effects3,2.",NC(CO)C(=O)NNCC1=C(O)C(O)=C(O)C=C1,"The combination of levodopa and benserazide is an anti-Parkinsonian agent,. Levodopa itself is the metabolic precursor of dopamine. In Parkinson's disease, dopamine is depleted to a large degree in the striatum, pallidum, and substantia nigra in the central nervous system (CNS),. The administration of levodopa to treat the disease is subsequently proposed to facilitate raises in the levels of available dopamine in these areas,. The metabolism of levodopa to dopamine occurs via the enzyme dopa decarboxylase, although unfortunately, this metabolism can also occur in extracerebral tissues,. As a result, the full therapeutic effect of an administered dose of levodopa may not be obtained if portions of it are catabolized outside of the CNS and various patient adherence diminishing extracerebral side effects due to the extracerebral presence of dopamine like nausea, vomiting, or even cardiac arrhythmias can also happen,.Subsequently, a peripheral decarboxylase inhibitor like benserazide, which blocks the extracerebral decarboxylation of levodopa, when administered in combination with levodopa has obvious and significant advantages. Such benefits include reduced gastrointestinal side effects, a more rapid and complete response at the initiation of therapy, and a simpler dosing regimen,.It is important to note, however, that benserazide is hydroxylated to trihydroxybenzylhydrazine in the intestinal mucosa and the liver,, and that as a potent inhibitor of the aromatic amino acid decarboxylase,,, it is this trihydroxybenzylhydrazine metabolite of benserazide that mainly protects levodopa against decarboxylation to dopamine in the gut and also around the rest of the body outside of the blood-brain barrier.Regardless, because Parkinson's disease progresses even with the therapy of levodopa and benserazide, this kind of combined therapy is only ever indicated if it is capable of improving the quality of life and adverse effect profile of using such drugs for Parkinson's patients and there is little to be gained by switching to or starting this combination therapy if patients are already being managed with stable, effective, and well-tolerated levadopa-only therapy,.Finally, it is also proposed that benserazide hydrochloride may be able to treat beta thalassaemia by maintaining the active expression of the gene for fetal hemoglobin so that constant production of fetal hemoglobin may replace the missing adult hemoglobin variation that is characteristic of patients with the condition, thereby decreasing the need for blood transfusion therapy.TargetActionsOrganismAAromatic-L-amino-acid decarboxylaseinhibitorHumans",[],"['Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Aromatic L-amino Acid Decarboxylase Inhibitors', 'Central Nervous System Agents', 'Dopamine Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hydrazines', 'Neurotransmitter Agents']" +DB00451,Levothyroxine,Levothyroxineis a synthetic T4 hormone used to treat hypothyroidism that can be used along with surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.,"['P06756', 'P05106', 'P10827', 'P10828']","Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4levels when a deficiency is present.Levothyroxine has a narrow therapeutic index and is titrated to maintain a euthyroid state with TSH (thyroid stimulating hormone) within a therapeutic range of 0.4–4.0 mIU/L.10Over- or under-treatment with levothyroxine may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function and glucose and lipid metabolism. The dose of levothyroxine should be titrated slowly and carefully and patients should be monitored for their response to titration to avoid these effects. TSH levels should be monitored at least yearly to avoid over-treating with levothyroxine which can result in hyperthyroidism (TSH <0.1mIU/L) and symptoms of increased heart rate, diarrhea, tremor, hypercalcemia, and weakness to name a few.16As many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status,7over-treatment with levothyroxine may result in increases in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. In populations with any cardiac concerns, levothyroxine should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease. Patients receiving concomitant levothyroxine and sympathomimetic agents should be monitored for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the levothyroxine dose or withhold for one week and restart at a lower dose.16Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase and suppressed serum parathyroid hormone levels. Administer the minimum dose of levothyroxine that achieves the desired clinical and biochemical response to mitigate this risk.Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing or discontinuing levothyroxine.",N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O,"Levothyroxine is a synthetically prepared levo-isomer of the thyroid hormone thyroxine (T, a tetra-iodinated tyrosine derivative) that acts as a replacement in deficiency syndromes such as hypothyroidism. Tis the major hormone secreted from the thyroid gland and is chemically identical to the naturally secreted T: it increases metabolic rate, decreases thyroid-stimulating hormone (TSH) production from the anterior lobe of the pituitary gland, and, in peripheral tissues, is converted to T. Thyroxine is released from its precursor protein thyroglobulin through proteolysis and secreted into the blood where is it then peripherally deiodinated to form triiodothyronine (T) which exerts a broad spectrum of stimulatory effects on cell metabolism. Tand Thave a relative potency of ~:.Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold.The thyroid hormones have been shown to exert both genomic and non-genomic effects.They exert their genomic effects by diffusing into the cell nucleus and binding to thyroid hormone receptors in DNA regions called thyroid hormone response elements (TREs) near genes.This complex of T, T, DNA, and other coregulatory proteins causes a conformational change and a resulting shift in transcriptional regulation of nearby genes, synthesis of messenger RNA, and cytoplasmic protein production.,For example, in cardiac tissues Thas been shown to regulate the genes for α- and β-myosin heavy chains, production of the sarcoplasmic reticulum proteins calcium-activated ATPase (Ca+-ATPase) and phospholamban, β-adrenergic receptors, guanine-nucleotide regulatory proteins, and adenylyl cyclase types V and VI as well as several plasma-membrane ion transporters, such as Na+/K+–ATPase, Na+/Ca+ exchanger, and voltage-gated potassium channels, including Kv., Kv., and Kv..As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status.The non-genomic actions of the thyroid hormones have been shown to occur through binding to a plasma membrane receptor integrin aVb at the Arg-Gly-Asp recognition site.From the cell-surface, Tbinding to integrin results in down-stream effects including activation of mitogen-activated protein kinase (MAPK; ERK/) and causes subsequent effects on cellular/nuclear events including angiogenesis and tumor cell proliferation.,TargetActionsOrganismAIntegrin alpha-VNot AvailableHumansAIntegrin beta-Not AvailableHumansAThyroid hormone receptor alphaagonistHumansAThyroid hormone receptor betaagonistHumans",[],"['Agents used to treat hypothyroidism', 'Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroid Products', 'Thyroxine-binding globulin substrates', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index']" +DB01087,Primaquine,Primaquineis an antimalarial indicated to prevent relapse of vivax malaria.,"['P08729', 'P16083']","Primaquine is an antimalarial agent and is the essential co-drug with chloroquine in treating all cases of malaria. In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. This stops the infection from continuing and allows the person to recover. Primaquine kills the intrahepatic form ofPlasmodium vivaxandPlasmodium ovale, and thereby prevents the development of the erythrocytic forms that are responsible for relapses (it also kills gametocytes). Primaquine is not used in the prevention of malaria, only in the treatment. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Primaquine has gametocytocidal activity against all plasmodia, includingP. falciparum.",COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1,"Primaquine's mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Also, although its mechanism of action is unclear, primaquine may bind to and alter the properties of protozoal DNA.TargetActionsOrganismAFe(II)-protoporphyrin IXantagonistPlasmodium falciparumUKeratin, type II cytoskeletal other/unknownHumansURibosyldihydronicotinamide dehydrogenase [quinone]inhibitorHumans",[],"['Aminoquinolines', 'Anti-Infective Agents', 'Antibiotics for Pneumocystis Pneumonia', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Methemoglobinemia Associated Agents', 'Moderate Risk QTc-Prolonging Agents', 'P-glycoprotein inhibitors', 'QTc Prolonging Agents', 'Quinolines']" +DB00970,Dactinomycin,Dactinomycinis an actinomycin used to treat a wide variety of cancers.,"['P11388', 'Q02880', 'P11387']","Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis.",[H][C@@]12CCCN1C(=O)[C@H](NC(=O)[C@@H](NC(=O)C1=C3N=C4C(OC3=C(C)C=C1)=C(C)C(=O)C(N)=C4C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@]3([H])CCCN3C(=O)[C@H](NC1=O)C(C)C)[C@@H](C)OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C2=O)C(C)C,"Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis.TargetActionsOrganismADNAadductHumansUDNA topoisomerase inhibitorHumansUDNA topoisomerase inhibitorHumans",[],"['Actinomycin', 'Actinomycines', 'Amino Acids, Peptides, and Proteins', 'Anti-Infective Agents', 'Antibiotics, Antineoplastic', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cytotoxic Antibiotics and Related Substances', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nucleic Acid Synthesis Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Peptides', 'Peptides, Cyclic', 'Protein Synthesis Inhibitors']" +DB00861,Diflunisal,"Diflunisalis an NSAID used to treat mild to moderate pain, inflammation, osteoarthritis, and rheumatoid arthritis.","['P35354', 'P23219']","Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure.",OC(=O)C1=C(O)C=CC(=C1)C1=C(F)C=C(F)C=C1,"The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antirheumatic Agents', 'Benzene Derivatives', 'Cyclooxygenase Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hydroxybenzoates', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Phenols', 'Photosensitizing Agents', 'Salicylates', 'Salicylic Acid and Derivatives', 'Sensory System Agents', 'UGT1A9 Inhibitors']" +DB00220,Nelfinavir,Nelfinaviris a viral protease inhibitor used in the treatment of HIV infection.,['O90777'],Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.,[H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CSC1=CC=CC=C1)NC(=O)C1=C(C)C(O)=CC=C1)[C@@H](C2)C(=O)NC(C)(C)C,"HIV viral protease is an important enzyme for HIV maturation and pathogenicity since HIV produces its structural and key proteins in the form of a polyprotein that needs to be cleaved by a protease.HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells.,The Gag-pol polyprotein undergoes proteolytic cleavage by HIV protease to produce molecular species which will assume conformational changes to become fully active.Inhibition of protease, therefore, prevents HIV virion from fully maturing and becoming infective.Nelfinavir is a competitive inhibitor of the HIV protease by reversibly binding to the active site of the enzyme, preventing it from interacting with its substrate to produce mature and infectious viral particles.,TargetActionsOrganismAHIV- proteaseinhibitorHuman Immunodeficiency Virus",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'BCRP/ABCG2 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'Isoquinolines', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'OCT1 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Protease Inhibitors', 'QTc Prolonging Agents', 'UGT1A1 Inducers', 'Viral Protease Inhibitors']" +DB08844,Uric acid,"Uric acid is the last product of purine metabolism in humans. The formation of uric acid is through the enzyme xanthine oxidase, which oxidizes oxypurines. Normally a small amount of uric acid is present in the body, but when there is an excess amount in the blood, called hyperuricemia, this can lead to gout and formation of kidney stones. As a therapeutic agent, it is known that uric acid is increased in response to oxidative stress, and as such, uric acid acts as an antioxidant. At present (August 2013), there is no approved formulation or indication for uric acid. In one country, Spain, uric acid is an investigational drug in a phase 3 trial studying its effects as an adjunct to alteplase in acute ischemic stroke.",['P06737'],"Uric acid is a strong reducing agent (donates electrons) and an antioxidant. Normally in humans, one of the main antioxidants in plasma is uric acid. Several animal studies have found that animals given exogenous uric acid within 3 hours after a stroke had decreased infarct volume, improved neurologic function, and diminished inflammatory responses providing evidence for the neuroprotective effects of uric acid. In some early human studies, uric acid has so far shown similar neuroprotective effects, in both the cortex and subcortex areas, due to its antioxidant effects such as decreased lipid peroxidation, and there appears to be no significant toxicities.",O=C1NC2=C(N1)C(=O)NC(=O)N2,"The exact mechanism of action for uric acid's antioxidant effects have not yet been elucidated.TargetActionsOrganismUGlycogen phosphorylase, liver formNot AvailableHumans",[],"['Alkaloids', 'Antioxidants', 'Biological Factors', 'Compounds used in a research, industrial, or household setting', 'Heterocyclic Compounds, Fused-Ring', 'Protective Agents', 'Purines', 'Purinones', 'Xanthine derivatives']" +DB00588,Fluticasone propionate,"Fluticasone propionateis a glucocorticoid used to treat asthma, inflammatory pruritic dermatoses, and nonallergic rhinitis.","['P04150', 'P06401', 'P47712', 'P08235']","Systemically, fluticasone propionate activates glucocorticoid receptors, and inhibits lung eosinophilia in rats10Label. Fluticasone propionate as a topical formulation is also associated with vasoconstriction in the skin9,3.",[H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C,"Fluticasone propionate works through an unknown mechanism to affect the action of various cell types and mediators of inflammation. Fluticasone propionate activates glucocorticoid receptors and inhibits lung eosinophilia in rats,.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUProgesterone receptoragonistHumansUCytosolic phospholipase AinhibitorHumansUMineralocorticoid receptorantagonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents to Treat Airway Disease', 'Androstadienes', 'Androstanes', 'Androstenes', 'Anti-Allergic Agents', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Central Nervous System Depressants', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Glucocorticoids', 'Immunosuppressive Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Steroids', 'Thyroxine-binding globulin inhibitors']" +DB00585,Nizatidine,Nizatidineis an H2 receptor antagonist used to treat GERD and a variety of ulcers.,['P25021'],"Nizatidine is a competitive, reversible inhibitor of histamine at the histamine H2-receptors, particularly those in the gastric parietal cells. By inhibiting the action of histamine on stomach cells, nizatidine reduces stomach acid production. Nizatidine had no demonstrable antiandrogenic action. Full-dose therapy for the problems treated by nizatidine lasts no longer than 8 weeks. It has been demonstrated that treatment with a reduced dose of nizatidine is effective as maintenance therapy following healing of active duodenal ulcers.",CNC(NCCSCC1=CSC(CN(C)C)=N1)=C[N+]([O-])=O,"Nizatidine competes with histamine for binding at the H-receptors on the gastric basolateral membrane of parietal cells. Competitive inhibition results in reduction of basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Acid Reducers', 'Agents Causing Muscle Toxicity', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Cholinesterase Inhibitors', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H2 Antagonists', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Sulfur Compounds', 'Thiazoles']" +DB01147,Cloxacillin,Cloxacillinis an antibiotic agent used for the treatment of beta-hemolytic streptococcal and pneumococcal infections as well as staphylococcal infections.,"['P0AEB2', 'P59676', 'Q8DR59']",Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin is for use against staphylococci that produce beta-lactamase.,[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cloxacillin interferes with an autolysin inhibitor.TargetActionsOrganismAD-alanyl-D-alanine carboxypeptidase DacAinhibitorEscherichia coli (strain K)APenicillin-binding protein XinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Resistant Penicillins', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Penicillinase-resistant Penicillins', 'Penicillins', 'Sulfur Compounds']" +DB13954,Estradiol cypionate,Estradiol cypionateis an estradiol prodrug used to treat vasomotor symptoms and hypoestrogenisms from hypogonadism.,"['P03372', 'Q92731', 'O75469', 'P43681', 'Q15596', 'Q99527', 'P00846', 'Q14457', 'P37059', 'P62508']","Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects9.",[H][C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(O)=CC=C4[C@@]3([H])CC[C@]12C)OC(=O)CCC1CCCC1,"Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause and of hypoestrogenism, which are primarily caused by a loss of estrogenic activity.TargetActionsOrganismAEstrogen receptor alphaagonistHumansAEstrogen receptor betaagonistHumansUNuclear receptor subfamily group I member Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNuclear receptor coactivator Not AvailableHumansUG-protein coupled estrogen receptor Not AvailableHumansUATP synthase subunit aNot AvailableHumansUBeclin-Not AvailableHumansUEstradiol -beta-dehydrogenase Not AvailableHumansUEstrogen-related receptor gammaligandHumans",[],"['Adrenal Cortex Hormones', 'BCRP/ABCG2 Inhibitors', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Estrogen Contraceptives', 'Estrogens', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein substrates', 'Reproductive Control Agents', 'Steroids', 'Thyroxine-binding globulin inducers', 'UGT1A1 Substrates']" +DB00518,Albendazole,Albendazoleis a benzimidazole anthelmintic used to treat parenchymal neurocysticercosis and other helminth infections.,"['F1L7U3', 'Q71U36', 'P68371', 'P83223']",Albendazole is a broad-spectrum anthelmintic. The principal mode of action for albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.,CCCSC1=CC2=C(C=C1)N=C(NC(=O)OC)N2,"Albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by diminishing its energy production, ultimately leading to immobilization and death of the parasite. It works by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. As cytoplasmic microtubules are critical in promoting glucose uptake in larval and adult stages of the susceptible parasites, the glycogen stores of the parasites are depleted. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth.TargetActionsOrganismATubulin beta- chaininhibitorPig roundwormNTubulin alpha-A chaininhibitorHumansNTubulin beta-B chaininhibitorHumansUFumarate reductase flavoprotein subunitinhibitorShewanella oneidensis (strain MR-)",[],"['Acids, Acyclic', 'Anthelmintics', 'Anti-Infective Agents', 'Anticestodal Agents', 'Antihelminthic', 'Antimitotic Agents', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiplatyhelmintic Agents', 'Benzimidazole Derivatives', 'Benzimidazoles', 'Carbamates', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strong)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Mitosis Modulators', 'P-glycoprotein substrates', 'Tubulin Modulators']" +DB00593,Ethosuximide,Ethosuximideis an anticonvulsant used to treat petit mal seizures.,['O43497'],"Used in the treatment of epilepsy. Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.",CCC1(C)CC(=O)NC1=O,"Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-G gives rise to T-type calcium currents. T-type calcium channels belong to the ""low-voltage activated (LVA)"" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.TargetActionsOrganismAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumans",[],"['Agents causing hyperkalemia', 'Anti-epileptic Agent', 'Antiarrhythmic agents', 'Anticonvulsants', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Imides', 'Nervous System', 'Potential QTc-Prolonging Agents', 'Pyrrolidines', 'Pyrrolidinones', 'QTc Prolonging Agents', 'Succinimide Derivatives', 'Succinimides']" +DB00409,Remoxipride,Remoxiprideis an discontinued atypical antipsychotic selective for dopamine D2 receptors.,"['P14416', 'P21917', 'P35462', 'P28223', 'Q99720']",Remoxipride is a weak selective dopamine D2receptor antagonist that was once used in the treatment of schizophrenia.1It has a moderate therapeutic index and duration of action.8Remoxipride was withdrawn due to deaths associated with aplastic anemia.5,CCN1CCC[C@H]1CNC(=O)C1=C(OC)C=CC(Br)=C1OC,"Remoxipride is an atypical antipsychotic dopamine Dantagonist.Chronic use upregulates the expression of Dreceptors, while downregulating the expression of Dand Dreceptors in the prefrontal cortex.This activity may be related to the antipsychotic activity of remoxipride.Remoxipride displays weaker binding to Ddopaminergic receptors that dopamine.This weaker binding is thought to account for the reduced incidence of Parkinsonism.Remoxipride also increases expression of the proteinFosin the nucleus accumbens but not the dorsolateral striatum, which may be responsible for a reduced incidence of extrapyramidal symptoms.TargetActionsOrganismADopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor Aother/unknownHumansUSigma non-opioid intracellular receptor antagonistHumans",[],"['Acids, Carbocyclic', 'Amides', 'Antipsychotic Agents', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Bromobenzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00233,Aminosalicylic acid,Aminosalicylic acidis an aminosalicylate drug used to induce remission in ulcerative colitis.,"['P35354', 'O15111', 'P09917', 'Q9NZK7']",Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic againstMycobacterium tuberculosis(prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.,NC1=CC(O)=C(C=C1)C(O)=O,"There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action againstMycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake byM. tuberculosis.TargetActionsOrganismUProstaglandin G/H synthase inhibitorHumansUInhibitor of nuclear factor kappa-B kinase subunit alphainhibitorHumansUArachidonate -lipoxygenaseinhibitorHumansUGroup IIE secretory phospholipase AunknownHumans",[],"['Acids, Carbocyclic', 'Aminobenzoates', 'Aminosalicylic Acid and Derivatives', 'Aminosalicylic Acids', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Benzene Derivatives', 'Benzoates', 'Drugs for Treatment of Tuberculosis', 'Hydroxy Acids', 'Hydroxybenzoates', 'Methemoglobinemia Associated Agents', 'para-Aminobenzoates', 'Phenols', 'Salicylates']" +DB00301,Flucloxacillin,"Flucloxacillinis a narrow spectrum penicillin antibiotic that exerts specific activity against Gram positive organisms in skin and soft tissue infections, except those caused by methicillin resistant staphylococcus aureus (MRSA).",['Q8XJ01'],"Flucloxacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name ""penicillin"" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Flucloxacillin hasin vitroactivity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Flucloxacillin results from the inhibition of cell wall synthesis and is mediated through flucloxacillin binding to penicillin binding proteins (PBPs). Flucloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1F)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, flucloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that flucloxacillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Resistant Penicillins', 'beta-Lactams', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Sulfur Compounds']" +DB00532,Mephenytoin,Mephenytoinis a phenylhydantoin used to treat refractory partial epilepsy.,"['Q14524', 'O75469']","Mephenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, mephenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Mephenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures.",CCC1(NC(=O)N(C)C1=O)C1=CC=CC=C1,"The mechanism of action of mephenytoin is not definitely known, but extensive research strongly suggests that its main mechanism is to block frequency-, use- and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUNuclear receptor subfamily group I member activatorHumans",[],"['Anti-epileptic Agent', 'Anticonvulsants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Hydantoins', 'Imidazoles', 'Imidazolidines', 'Nervous System', 'Thyroxine-binding globulin substrates']" +DB00647,Dextropropoxyphene,Dextropropoxypheneis an opioid analgesic used to treat mild to moderate pain.,"['P35372', 'P41143', 'P41145', 'P23141', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391']","Propoxyphene, a synthetic opiate agonist, is structurally similar to methadone. Its general pharmacologic properties are those of the opiates as a group. The analgesic effect of propoxyphene is due to the d-isomer, dextropropoxyphene. It binds to the opiate receptors and leads to a decrease of the perception of pain stimuli. Propoxyphene possesses little to no antitussive activity and no antipyretic action.",CCC(=O)O[C@@](CC1=CC=CC=C1)([C@H](C)CN(C)C)C1=CC=CC=C1,"Propoxyphene acts as a weak agonist at OP, OP, and OP opiate receptors within the central nervous system (CNS). Propoxyphene primarily affects OP receptors, which are coupled with G-protein receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as propoxyphene also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (OP-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP and OP receptor agonist). This results in hyperpolarization and reduced neuronal excitability.TargetActionsOrganismAMu-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansAKappa-type opioid receptorantagonistHumansULiver carboxylesterase Not AvailableHumansUNMDA receptorantagonistHumans",[],"['Acids, Acyclic', 'Agents that reduce seizure threshold', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diphenylpropylamine Derivatives', 'High-risk opioids', 'Narcotics', 'Nervous System', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Propionates', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00247,Methysergide,Methysergideis an ergot alkaloid used for the prophylaxis of migraine and cluster headaches.,"['P41595', 'P28335', 'P28223', 'P08908', 'P34969', 'P28222', 'P30939', 'P28566']","Methysergide has been shown,in vitroandin vivo, to inhibit or block the effects of serotonin, a substance which may be involved in the mechanism of vascular headaches. Serotonin has been variously described as a central neurohumoral agent or chemical mediator, as a ""headache substance"" acting directly or indirectly to lower pain threshold, as an intrinsic ""motor hormone"" of the gastrointestinal tract, and as a ""hormone"" involved in connective tissue reparative processes.",[H][C@@]12CC3=CN(C)C4=C3C(=CC=C4)C1=C[C@H](CN2C)C(=O)NC(CC)CO,"Methysergide is serotonin antagonists acts on central nervous system (CNS), which directly stimulates the smooth muscle leading to vasoconstriction. Some alpha-adrenergic blocking activity has been reported. Suggestions have been made by investigators as to the mechanism whereby Methysergide produces its clinical effects, but this has not been finally established, although it may be related to the antiserotonin effect.TargetActionsOrganismA-hydroxytryptamine receptor BantagonistHumansA-hydroxytryptamine receptor CantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor AagonistHumansA-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor BbinderHumansU-hydroxytryptamine receptor FbinderHumansU-hydroxytryptamine receptor EbinderHumans",[],"['Agents that produce hypertension', 'Alkaloids', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Heterocyclic Compounds, Fused-Ring', 'Lysergic Acid', 'Nervous System', 'Neurotransmitter Agents', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Vasoconstrictor Agents']" +DB01332,Ceftizoxime,"Ceftizoximeis a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including lower respiratory tract infection, urinary tract infection, and gonorrhea.","['P02918', 'P02919', 'P08506']",Ceftizoxime is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders.,[H][C@]12SCC=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O,"Ceftizoxime is an aminothiazolyl cephalosporin with an extended spectrum of activity against many gram-negative, nosocomially acquired pathogens. It has excellent beta-lactamase stability, with good in vitro activity against Haemophilus influenzae, Neisseria gonorrhoeae and Klebsiella pneumoniae. Ceftizoxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that ceftizoxime interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)UPeptidoglycan transpeptidasebinderUD-alanyl-D-alanine carboxypeptidase DacCbinderEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB01327,Cefazolin,"Cefazolinis a broad-spectrum cephalosporin antibiotic mainly used for the treatment of skin bacterial infections and other moderate to severe bacterial infections in the lung, bone, joint, stomach, blood, heart valve, and urinary tract.","['P02918', 'P02919', 'P76577', 'P0AD65', 'P0AD68', 'P27169', 'P40933', 'P60568']",Cefazolin (also known as cefazoline or cephazolin) is a semi-synthetic first generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.,[H][C@]12SCC(CSC3=NN=C(C)S3)=C(N1C(=O)[C@H]2NC(=O)CN1C=NN=N1)C(O)=O,"In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.TargetActionsOrganismAPenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein CinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorEscherichia coli (strain K)APeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)USerum paraoxonase/arylesterase inhibitorHumansUInterleukin-inhibitorHumansUInterleukin-inhibitorHumans",['Antibiotic pre-surgical prophylaxis'],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'First-Generation Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Sulfur Compounds', 'Thiazines']" +DB01326,Cefamandole,"Cefamandoleis a beta-lactam antibiotic used in the treatment of various infections caused by susceptible strains of bacteria, such as lower respiratory infections, urinary tract infections, skin infections, and bone and joint infections.",['Q70KI2'],The parenteral prodrug formate ester cefamandole nafate is a broad-spectrum cephalosporin antibiotic. The bactericidal action of cefamandole results from inhibition of cell-wall synthesis. Cephalosporins have in vitro activity against a wide range of gram-positive and gram-negative organisms.,[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)[C@H](O)C1=CC=CC=C1)C(O)=O,"Like all beta-lactam antibiotics, cefamandole binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefamandole interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorBacteroides fragilis",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB01438,Phenazopyridine,"Phenazopyridineis a local anesthetic used for the symptomatic relief of pain, burning, urgency, frequency, and general discomfort caused by lower urinary tract irritations that are a result of infection, trauma, surgery, endoscopic procedures, or the passage of equipment or catheters.",['P35498'],"Phenazopyridine acts as a local anesthetic offering relief from irritating conditions of the urinary tract. It relieves urinary urgency frequency, burning, pain, and discomfort.14,18A note on urine and skin discoloration and interference with test resultsYellowing of the skin or sclerae of the eyes may indicate that the accumulation of phenazopyridine has occurred. This may be a consequence of overdose, decreased renal function, taking the drug for over two days. Elderly patients may be at particular risk due to a decline in renal function, potentiating the risk of phenazopyridine accumulation. The drug should be discontinued if yellowing of the skin or sclerae is observed.14Hemolytic anemia is a risk of phenazopyridine, especially in cases of overdose. In addition to the above effects, this drug may impart an orange or red color of urine and feces, causing staining of clothing. Other body fluids may also be stained, and in patients wearing contact lenses, phenazopyridine may cause lens staining. Due to its orange-red color, this drug may interfere with laboratory requiring colorimetric, spectrophotometric or fluorometric methods of analysis.14In patients with G6PD enzyme deficiency, this drug poses a greater risk of hemolysis, even at normal doses and is not recommended.14A note on carcinogenesisBased on the results of in vivo studies in rats, this drug has been listed as a carcinogen in the USA since 1981. Rats given this drug were found to demonstrate increased rates of hepatocellular carcinoma and colorectal tumors.23Use this agent with caution and limit the administration of this drug when possible.",NC1=NC(N)=C(C=C1)\N=N\C1=CC=CC=C1,"The full mechanism of action of phenazopyridine is not fully elucidated, however, it is reported to exert a direct topical analgesic effect on the mucosal lining of the urinary tract via the inhibition of voltage-gated sodium channelsand possibly group A nerve fibers, as suggested by the results of a study in rats.The above actions likely lead to the relief of unpleasant urinary symptoms.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUGroup A nerve fibersinhibitorRat",[],"['Amines', 'Aminopyridines', 'Antipruritics and Local Anesthetics', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Methemoglobinemia Associated Agents', 'Nephrotoxic agents', 'Pyridines', 'Urologicals']" +DB01329,Cefoperazone,"Cefoperazoneis a broad-spectrum cephalosporin antibiotic used for the treatment of bacterial infections in various locations, including the respiratory tract, abdomen, skin, and female genital tracts.","['P0AD68', 'P02919', 'P0AD65', 'Q07806', 'Q9X6W0', 'P08506', 'P02918', 'P0AEB2', 'P24228']",Cefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis,[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@@]2([H])NC(=O)[C@H](NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=C(O)C=C1)C(O)=O,"Like all beta-lactam antibiotics, cefoperazone binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.TargetActionsOrganismAPeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorPseudomonas aeruginosa (strain ATCC / PAO / C / PRS / LMG )APenicillin-binding protein BinhibitorPseudomonas aeruginosaAD-alanyl-D-alanine carboxypeptidase DacCinhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacAinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacBinhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB09555,Dexchlorpheniramine maleate,"Dexchlorpheniramine maleateis a first generation antihistamine used to treat allergic and vasomotor rhinitis, allergic conjunctivitis, and mild urticaria and angioedema.",['P35367'],"In allergic reactions, an allergen binds to IgE antibodies on mast cells and basophils. Once this occurs IgE receptors crosslink with each other triggering a series of events that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Dexchlorpheniramine, is a histamine H1 antagonist of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",OC(=O)\C=C/C(O)=O.CN(C)CC[C@@H](C1=CC=C(Cl)C=C1)C1=CC=CC=N1,"Competes with histamine for H-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. Dexchlorpheniramine is the predominant active isomer of chlorpheniramine and is approximately twice as active as the racemic compound.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Agents that reduce seizure threshold', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Inhibitors', 'Pyridines', 'QTc Prolonging Agents', 'Stereoisomerism']" +DB00749,Etodolac,"Etodolacis an NSAID used to treat osteoarthritis and rheumatoid arthritis, as well as acute pain.","['P35354', 'P23219', 'P19793']","Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversionin vivo.",CCC1=C2NC3=C(CCOC3(CC)CC(O)=O)C2=CC=C1,"Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be – times more selective for COX- than COX-. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumansURetinoic acid receptor RXR-alphaotherHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Indoleacetic Acids', 'Indoles', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB01124,Tolbutamide,Tolbutamideis a sulfonylurea used to treat hyperglycemia in patients with type 2 diabetes mellitus.,"['Q09428', 'P48048']","Tolbutamide, a first-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Tolbutamide is twice as potent as the related second-generation agent glipizide. Tolbutamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must be able to produce insulin for this drug to work.",CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1,"Sulfonylureas lower blood glucose in patients with NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor (receptor ) on the beta cell. Sulfonylureas inhibit the ATP-potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis, an effect similar to that of glucose.TargetActionsOrganismAATP-binding cassette sub-family C member inhibitorHumansUATP-sensitive inward rectifier potassium channel inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diagnostic Agents', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'OAT1/SLC22A6 inhibitors', 'OATP2B1/SLCO2B1 substrates', 'Oral Hypoglycemics', 'Sulfonamides', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds', 'Tests for Diabetes']" +DB00190,Carbidopa,Carbidopais a dopa decarboxylase inhibitor used in combination with levodopa for the symptomatic treatment of idiopathic Parkinson disease and other conditions associated with parkinsonian symptoms.,['P20711'],"When mixed withlevodopa, carbidopa inhibits the peripheral conversion oflevodopato dopamine and the decarboxylation ofoxitriptanto serotonin by aromatic L-amino acid decarboxylase. This results in an increased amount oflevodopaandoxitriptanavailable for transport to the central nervous system. Carbidopa also inhibits the metabolism oflevodopain the GI tract, thus, increasing the bioavailability oflevodopa.4The presence of additional units of circulatinglevodopacan increase the effectiveness of the still functional dopaminergic neurons and it has been shown to alleviate symptoms for a time. The action of carbidopa is very important aslevodopais able to cross the blood-brain barrier while dopamine cannot.8Hence the administration of carbidopa is essential to prevent the transformation of externallevodopato dopamine before reaching the main action site in the brain.The coadministration of carbidopa withlevodopahas been shown to increase the half-life oflevodopamore than 1.5 times while increasing the plasma level and decreasing clearance. The combination therapy has also shown an increase of the recovery oflevodopain urine instead of dopamine which proves a reduced metabolism. This effect has been highly observed by a significant reduction inlevodoparequirements and a significant reduction in the presence of side effects such as nausea. It has been observed that the effect of carbidopa is not dose-dependent.9",C[C@@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O,"Carbidopa is an inhibitor of the DDC which in order, inhibits the peripheral metabolism of levodopa.DDC is very important in the biosynthesis of L-tryptophan to serotonin and the modification of L-DOPA to dopamine.DDC can be found in the body periphery and in the blood-brain barrier.The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier.Hence, it will prevent the metabolism oflevodopain the periphery but it will not have any activity on the generation of dopamine in the brain.TargetActionsOrganismAAromatic-L-amino-acid decarboxylaseinhibitorHumans",[],"['Amines', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Aromatic Amino Acid Decarboxylase Inhibitors', 'Aromatic L-amino Acid Decarboxylase Inhibitors', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Catecholamines', 'Catechols', 'Central Nervous System Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hydrazines', 'Phenols']" +DB01086,Benzocaine,"Benzocaineis a topical local anesthetic used for the temporary relief of pain and itching associated with minor burns, sunburn, scrapes and insect bites or minor skin irritations.",['Q9Y5Y9'],"Benzocaine is indicated for use as a topical anesthetic.4It has a duration of action of approximately 10 minutes9and a wide therapeutic window.4Patients should be counselled regarding the risks of methemoglobinemia.4,5,6,8",CCOC(=O)C1=CC=C(N)C=C1,"Benzocaine diffuses into nerve cells where it binds to sodium channels, preventing the channels from opening, and blocking the influx of sodium ions.,,Nerve cells unable to allow sodium into cells cannot depolarize and conduct nerve impulses.,TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",['Buccopharyngeal anesthesia'],"['Acids, Carbocyclic', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Aminobenzoates', 'Anesthetics', 'Anesthetics for Topical Use', 'Anesthetics, Local', 'Antipruritics and Local Anesthetics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Benzene Derivatives', 'Benzoates', 'Cell-mediated Immunity', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Esters of Aminobenzoic Acid', 'Increased Histamine Release', 'Local Anesthetics (Ester)', 'Methemoglobinemia Associated Agents', 'Nervous System', 'P-glycoprotein inhibitors', 'para-Aminobenzoates', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Standardized Chemical Allergen', 'Throat Preparations', 'Vasoprotectives']" +DB00784,Mefenamic acid,"Mefenamic acidis an NSAID used to treat mild to moderate pain for no more than a week, and primary dysmenorrhea.","['P35354', 'P23219']","Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase.",CC1=C(C)C(NC2=CC=CC=C2C(O)=O)=CC=C1,"Mefenamic acid binds the prostaglandin synthetase receptors COX- and COX-, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amines', 'Aminobenzoates', 'Analgesics', 'Analgesics, Non-Narcotic', 'Aniline Compounds', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Fenamates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'ortho-Aminobenzoates', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Sensory System Agents', 'UGT1A9 Inhibitors', 'UGT2B7 Inhibitors']" +DB01131,Proguanil,Proguanilis a medication indicated for prophylaxis and treatment of Plasmodium falciparum malaria.,"['P00374', 'P13922']",Proguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity againstP. falciparumand cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines.,CC(C)NC(=N)NC(=N)NC1=CC=C(Cl)C=C1,"Proguanil inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.TargetActionsOrganismADihydrofolate reductaseinhibitorHumansUBifunctional dihydrofolate reductase-thymidylate synthaseinhibitorPlasmodium falciparum (isolate K / Thailand)",[],"['Amidines', 'Anti-Infective Agents', 'Antimalarials', 'Antimetabolites', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Biguanides', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Folic Acid Antagonists', 'Guanidines', 'Noxae', 'Toxic Actions']" +DB00672,Chlorpropamide,Chlorpropamideis a sulfonylurea used in the treatment of non insulin dependent diabetes mellitus.,['Q09428'],"Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Chlorpropamide is twice as potent as the related second-generation agent glipizide.",CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1,"Sulfonylureas such as chlorpropamide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.TargetActionsOrganismAATP-binding cassette sub-family C member inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'OAT1/SLC22A6 inhibitors', 'Oral Hypoglycemics', 'Sulfonamides', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB00227,Lovastatin,"Lovastatinis an HMG-CoA reductase inhibitor used to lower LDL cholesterol and reduce the risk of cardiovascular disease and associated conditions, including myocardial infarction and stroke.","['P04035', 'P20701', 'Q92769']","Lovastatin is an oral antilipemic agent which reversibly inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, lovastatin reduces the risk of cardiovascular morbidity and mortality.5,13,14,30Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.13Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.17,18,19,20,21Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.13,14Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.5,24,23Clinical studies have shown that lovastatin reduces LDL-C and total cholesterol by 25-40%.5The 50% inhibitory dose is known to be of 46 mcg/kg which is translated into a reduction of approximately 30% of plasma cholesterol.2Myopathy/RhabdomyolysisLovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is dose-related and is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. In a clinical study (EXCEL)30in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20 to 40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily.Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may also be at increased risk for myopathy. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued.The risk of myopathy during treatment with lovastatin may be increased with concurrent administration of interacting drugs such asfenofibrate,niacin,gemfibrozil,cyclosporine, and strong inhibitors of the CYP3A4 enzyme. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered withcolchicine, and caution should therefore be exercised when prescribing these two medications together.43,44Real-world data from observational studies has suggested that 10-15% of people taking statins may experience muscle aches at some point during treatment.38Liver DysfunctionPersistent increases (to more than 3 times the upper limit of normal) in serum transaminases occurred in 1.9% of adult patients who received lovastatin for at least one year in early clinical trials. When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases usually appeared 3 to 12 months after the start of therapy with lovastatin, and were not associated with jaundice or other clinical signs or symptoms.43In the EXCEL study,30the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% at 20 mg/day, 0.9% at 40 mg/day, and 1.5% at 80 mg/day in patients on lovastatin. However, in post-marketing experience with lovastatin, symptomatic liver disease has been reported rarely at all dosages.43",[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC,"Lovastatin is a lactone which is readily hydrolyzedin vivoto the corresponding β-hydroxyacid and strong inhibitor of HMG-CoA reductase, a hepatic microsomal enzyme which catalyzes the conversion of HMG-CoA (-hydroxy--methylglutaryl-coenzyme A ) to mevalonate, an early rate-limiting step in cholesterol biosynthesis.,At therapeutic lovastatin doses, HMG-CoA reductase is not completely blocked, thereby allowing biologically necessary amounts of mevalonate to be available. Because the conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with lovastatin would not be expected to cause an accumulation of potentially toxic sterols.Lovastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increase hepatic uptake of LDL. Lovastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL and a significant reduction in the risk of development of CVD and all-cause mortality.,,,,A significant effect on LDL-C reduction was seen within weeks of initiation of lovastatin, and the maximum therapeutic response occurred within - weeks. The response was maintained during continuation of therapy. Single daily doses given in the evening were more effective than the same dose given in the morning, perhaps because cholesterol is synthesized mainly at night. When therapy with lovastatin is stopped, total cholesterol has been shown to return to pre-treatment levels.In vitro and in vivo animal studies also demonstrate that lovastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.Statins have also been found to bind allosterically to β integrin function-associated antigen- (LFA-), which plays an important role in leukocyte trafficking and in T cell activation.Lovastatin has been reported to have beneficial effects on certain cancers. This includes a multi-factorial stress-triggered cell death (apoptosis) and DNA degradation response in breast cancer cells.It has also been shown to inhibit histone deacetylase (HDAC) activity and increase the accumulation of acetylated histone-H and the expression of p(WAF/CIP) in human cancer cells, suggesting that statins might serve as novel HDAC inhibitors for cancer therapy and chemoprevention.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUIntegrin alpha-LinhibitorHumansNHistone deacetylase inhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Regulating Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB01142,Doxepin,"Doxepinis a psychotropic agent used for the treatment of depression, anxiety, manic-depressive disorder, and insomnia.","['P35367', 'P25021', 'P23975', 'P31645', 'P28223', 'P41595', 'P28335', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P35348', 'P35368', 'P25100', 'P08908', 'P50406', 'Q9H3N8', 'Q12809']","Similar to other tricyclic antidepressants, doxepin was shown, in preclinical trials, to decrease the electrical activity of the brain, prolong the hexobarbital-induced sleep and block avoidance behavior without affecting the conditioned emotional response. At high doses, it also produces symptoms of central nervous system depression.20Doxepin is known to cause antidepressant, sedative, and anticholinergic effects. At high doses, its anticholinergic and antiadrenergic properties are the most prevalent which limit its efficacy. These effects are observed at high doses where its affinity for H1 histamine receptor is lost and its binding to other receptors is observed.1The maximal antidepressive effects of doxepin are present around two weeks following initiation of therapy.6However, the sedative effects of doxepin, usually used for the treatment of insomnia or anxiety, are observed immediately after administration.7",[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12,"Doxepin exact mechanism of action is not very clear. However, doxepin is known to be a selective histamine H receptor blocker.This effect on histamine receptors indicates effectiveness in skin conditions.Breaking its function according to the different effect, doxepin's antidepressive action is primarily associated with the inhibition of the central nervous system biogenic amine reuptake; more specifically, norepinephrine and serotonin at synaptic nerve terminals. This effect increases the level of monoamines in the synaptic site which in order increases the activity at the post-synaptic neuron receptor sites.It has been suggested that doxepin also desensitizes both serotonin A receptors and beta-adrenergic receptors.It is known that the lack of dopamine transporters in the frontal cortex and the transmission of dopamine in this region is largely inactivated by the effect of norepinephrine reuptake. Hence, doxepin action on the frontal cortex is suggested to increase dopamine neurotransmission in this area.TargetActionsOrganismAHistamine H receptorantagonistHumansAHistamine H receptorantagonistHumansASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor binderHumansUHistamine H receptorbinderHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Acid Reducers', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Antipruritics and Local Anesthetics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Dibenzoxepins', 'Drugs that are Mainly Renally Excreted', 'Ethers, Cyclic', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H2 Antagonists', 'Hypnotics and Sedatives', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Sleep Aids, Pharmaceutical', 'Tertiary amine tricyclic antidepressants', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB00461,Nabumetone,Nabumetoneis an NSAID used to treat osteoarthritis and rheumatoid arthritis.,"['P35354', 'P23219']","NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia.9,6This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited.The anti-inflammatory effect of NSAIDs is mediated by preventing vasodilation, increases in vascular permeability, and the release of cytokines from endothelial cells.9,7These three effects together prevent immunocompetent cells from migrating to the site of injury thereby preventing additional damage and inflammation due to activation of the immune system at the site of damage. PGs also modulate T-helper cell activation and differentiation, an activity which is thought to be of importance in arthritic conditions.The anti-pyretic effect of NSAIDs is mediated through preventing increases in temperature by prostaglandins (PGs) via the hypothalamus.9Activation of this process by other inflammatory mediators relies upon subsequent action by PGs, therefore NSAIDs are able to reduce fever due to these mediators as well.The adverse effects of NSAIDs are related to their therapeutic effects.9The same vasodilatory action which occurs in inflammation also serves to regulate blood flow to the kidneys through the afferent renal arteries. NSAIDs are widely known as nephrotoxic agents as the reduction in PGs produces vasoconstriction of these arteries resulting in reduced blood flow to the kidneys and a subsequent decline in renal function. Reductions in mucus and HCO3-secretion in the stomach increases the risk of ulceration by limiting the protection mediated by PGs. Lastly, COX-2 selective agents like nabumetone can unbalance prothrombotic and antithrombotic prostanoid generation leading to increased platelet aggregation and increased risk of thrombosis.",COC1=CC2=C(C=C1)C=C(CCC(C)=O)C=C2,"Nabumetone's active metabolite, -MNA, is an inhibitor of both COX- and COX- although it exhibits some COX- selectivity.Label,Inhibition of COX- and COX- reduces conversion of arachidonic acid to PGs and thromboxane (TXA). This reduction in prostanoid production is the common mechanism that mediates the effects of nambutone.PGEis the primary PG involved in modulation of nociception.It mediates peripheral sensitization through a variety of effects.,PGEactivates the Gq-coupled EPreceptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGEalso activates the EPreceptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member (TRPV) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the PX purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGEact via EPto increase sensitivity to bradykinin and via EPto further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EPreceptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGIis known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.PGIand PGEcontribute to acute inflammation via their IP and EPreceptors.,Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGEalso contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.PGDplays a role in the activation of endothelial cell release of cytokines through its DPreceptor.PGIand PGEmodulate T-helper cell activation and differentiation through IP, EP, and EPreceptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.PGEcan cross the blood-brain barrier and act on excitatory GqEPreceptors on thermoregulatory neurons in the hypothalamus.This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGEthereby reducing the activity of these neurons.The adverse effects of NSAIDs stem from the protective and regulatory roles of prostanoids which have been well-characterized.PGIand PGEregulate blood flow to the kidney by similar mechanisms to the vasodilation they produce in inflammation. Prevention of this regulation by NSAIDs produces vasoconstriction which limits renal function by reducing blood flow and the hydrostatic pressure which drives filtration. PGEalso regulates gastric protection via EPreceptors which are, in this location, coupled to Giwhich inhibits the AC/PKA pathway. This reduces the secretion of protons by H+/K+ATPase in parietal cells and increases the secretion of mucus and HCO-by superficial endothelial cells. Disruption of this protective action by NSAIDs lead to ulceration of the gastric mucosa. Lastly, disruption of PGI, which opposes platelet aggregation, generation by COX- selective agents leads to an imbalance with TXAgenerated by COX-, which promotes aggregation of platelets, leading to increased risk of thrombosis. Since nabumetone is somewhat COX- selective it is thought to promote this imbalance and increase thrombotic risk.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Butanones', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Ketones', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Other Nonsteroidal Anti-inflammatory Agents', 'Photosensitizing Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)']" +DB00440,Trimethoprim,"Trimethoprimis an antifolate antibiotic often used in combination with sulfamethoxazole to treat a number of infections, including those of the urinary tract, respiratory tract, and gastrointestinal tract.",['P0ABQ4'],"Trimethoprim exerts its antimicrobial effects by inhibiting an essential step in the synthesis of bacterial nucleic acids and proteins.14It has shown activity against several species of gram-negative bacteria, as well as coagulase-negativeStaphylococcusspecies.14Resistance to trimethoprim may arise via a variety of mechanisms, including alterations to the bacterial cell wall, overproduction of dihydrofolate reductase, or production of resistant dihydrofolate reductase.14Rarely, trimethoprim can precipitate the development of blood disorders (e.g. thrombocytopenia, leukopenia, etc.) which may be preceded by symptoms such as sore throat, fever, pallor, and or purpura - patients should be monitored closely for the development of these symptoms throught the course of therapy.14As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.",COC1=CC(CC2=CN=C(N)N=C2N)=CC(OC)=C1OC,"Trimethoprim is a reversible inhibitor of dihydrofolate reductase, one of the principal enzymes catalyzing the formation of tetrahydrofolic acid (THF) from dihydrofolic acid (DHF).Tetrahydrofolic acid is necessary for the biosynthesis of bacterial nucleic acids and proteins and ultimately for continued bacterial survival - inhibiting its synthesis, then, results in bactericidal activity. Trimethoprim binds with a much stronger affinity to bacterial dihydrofolate reductase as compared to its mammalian counterpart, allowing trimethoprim to selectively interfere with bacterial biosynthetic processes.Trimethoprim is often given in combination with sulfamethoxazole, which inhibits the preceding step in bacterial protein synthesis - given together, sulfamethoxazole and trimethoprim inhibit two consecutive steps in the biosynthesis of bacterial nucleic acids and proteins.As a monotherapy trimethoprim is considered bacteriostatic, but in combination with sulfamethoxazole is thought to exert bactericidal activity.,TargetActionsOrganismADihydrofolate reductaseinhibitorEscherichia coli (strain K)",[],"['Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antibiotics for Pneumocystis Pneumonia', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Folic Acid Antagonists', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 2 Inhibitors', 'MATE 2 Substrates', 'MATE inhibitors', 'MATE substrates', 'OCT2 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Pyrimidines', 'Renal Agents', 'Sulfonamides and trimethoprim', 'Trimethoprim and Derivatives']" +DB00778,Roxithromycin,Roxithromycinis an antibiotic used to treat a variety of susceptible bacterial infections.,"['P0A7J6', 'P08183']","Roxithromycin has the following antibacterial spectrumin vitro:Streptococcus agalactiae,Streptococcus pneumoniae(Pneumococcus),Neisseria meningitides(Meningococcus),Listeria monocytogenes,Mycoplasma pneumoniae,Chlamydia trachomatis,Ureaplasma urealyticum,Legionella pneumophila,Helicobacter(Campylobacter),Gardnerella vaginalis,Bordetella pertussis,Moraxella catarrhalis(Branhamella Catarrhalis), andHaemophilus ducreyi. Roxithromycin is highly concentrated in polymorphonuclear leukocytes and macrophages, achieving intracellular concentrations greater than those outside the cell. Roxithromycin enhances the adhesive and chemotactic functions of these cells which in the presence of infection produce phagocytosis and bacterial lysis. Roxithromycin also possesses intracellular bactericidal activity.",CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)C(=NOCOCCOC)[C@H](C)[C@@H](O)[C@]1(C)O,Roxithromycin prevents bacterial growth by interfering with their protein synthesis. It binds to the S subunit of bacterial ribosomes and inhibits the translocation of peptides.TargetActionsOrganismAS ribosomal protein LinhibitorShigella flexneriUP-glycoprotein Not AvailableHumans,[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Erythromycin and similars', 'Lactones', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'Moderate Risk QTc-Prolonging Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Polyketides', 'QTc Prolonging Agents']" +DB00870,Suprofen,Suprofenis an NSAID used to prevent pupil constriction in ocular surgery.,"['P23219', 'P35354']","Suprofen is a non-steroidal anti-inflammatory analgesic and antipyretic. Ophthalmic anti-inflammatory medicines are used in the eye to lessen problems that can occur during or after some kinds of eye surgery. Sometimes, the pupil of the eye gets smaller during an operation (pupil constriction), making it more difficult for the surgeon to reach some areas of the eye. Suprofen is used to help prevent this.",CC(C(O)=O)C1=CC=C(C=C1)C(=O)C1=CC=CS1,"Suprofen binds to the cyclooxygenase- (COX-) and cyclooxygenase- (COX-) isoenzymes, preventing the synthesis of prostaglandins and reducing the inflammatory response. Cyclooxygenase catalyses the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. The overall result is a reduction in pain and inflammation in the eyes and the prevention of pupil constriction during surgery. Normally trauma to the anterior segment of the eye (especially the iris) increases endogenous prostaglandin synthesis which leads to constriction of the iris sphincter.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Phenylpropionates', 'Propionates', 'Sensory System Agents', 'UGT1A1 Substrates', 'UGT2B7 substrates']" +DB00384,Triamterene,Triamtereneis a potassium-sparing diuretic used in the treatment of edema and in the management of hypertension.,"['P51170', 'P37088', 'P51168', 'P51172']","Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypertension and edema. It primarily works on the distal nephron in the kidneys; it acts from the late distal tubule to the collecting duct to inhibit Na+ reabsorption and decreasing K+ excretion.11As triamterene tends to conserve potassium more strongly than promoting Na+ excretion, it can cause an increase in serum potassium, which may result in hyperkalemia potentially associated with cardiac irregularities.15In healthy volunteers administered with oral triamterene, there was an increase in the renal clearnace of sodium and magnesium, and a decrease in the clearance of uric acid and creatinine5due to its effect of reducing glomerular filtration renal plasma flow.13Triamterene does not affect calcium excretion.13In clinical trials, the use of triamterene in combination with hydrochlorothiazide resulted an enhanced blood pressure-lowering effects of hydrochlorothiazide.7",NC1=NC(N)=C2N=C(C(N)=NC2=N1)C1=CC=CC=C1,"Triamterene inhibits the epithelial sodium channels (ENaC) located on the lumenal side in the late distal convoluted tubule and collecting tubule, which are transmembrane channels that normally promote sodium uptake and potassium secretion.In the late distal tubule to the collecting duct, sodium ions are actively reabsorbed via ENaC on the luminal membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase,with water following passively.Triamterene exerts a diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium ions in exchange for potassium and hydrogen ions and its natriuretic activity is limited by the amount of sodium reaching its site of action.Its action is antagonistic to that of adrenal mineralocorticoids, such as aldosterone, but it is not an inhibitor or antagonist of aldosterone.Triamterene maintains or increases sodium excretion, thereby increasing the excretion of water, and reducing the excess loss of potassium, hydrogen, and chloride ions by inhibiting the distal tubular exchange mechanism.Due to its diuretic effect, triamterene rapidly and reversibly reduces the lumen-negative transepithelial potential difference by almost completely abolishing Na+ conductance without altering K+ conductance.This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion.Triamterene is similar in action toamiloridebut, unlike amiloride, increases the urinary excretion of magnesium.TargetActionsOrganismAAmiloride-sensitive sodium channel subunit gammainhibitorHumansAAmiloride-sensitive sodium channel subunit alphainhibitorHumansAAmiloride-sensitive sodium channel subunit betainhibitorHumansUAmiloride-sensitive sodium channel subunit deltainhibitorHumans",[],"['Agents causing hyperkalemia', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Decreased Renal K+ Excretion', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Epithelial Sodium Channel Blockers', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Increased Diuresis', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Nephrotoxic agents', 'Photosensitizing Agents', 'Potassium-Sparing Diuretics', 'Pteridines', 'Sodium Channel Blockers']" +DB00417,Phenoxymethylpenicillin,"Phenoxymethylpenicillinis a penicillin antibiotic used to prevent and treat mild to moderately severe infections in the respiratory tract, skin, and soft tissues.","['Q53707', 'Q8XJ01', 'P24228', 'P12256', 'P46059']","Phenoxymethylpenicillin works against penicillin-sensitive microorganisms with bactericidal effects. It targets the bacteria during its active multiplication stage by interfering with bacterial cell wall peptidoglycan synthesis.In vitro, phenoxymethylpenicillin was shown to be active against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L and M), and pneumococci, as well asCorynebacterium diphtheriae,Bacillus anthracis, Clostridia,Actinomyces bovis,Streptobacillus moniliformis,Listeria monocytogenes,Leptospira,Neisseria gonorrhoeae, andTreponema pallidum.Label",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)COC1=CC=CC=C1)C(O)=O,"Phenoxymethylpenicillin inhibits the biosynthesis of cell wall mucopeptideLabelby binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, which are critical in the cell wall synthesis and maintenance, as well as cell division.This disrupts the third and last stage of bacterial cell wall synthesis. This subsequently leads to cell lysis.TargetActionsOrganismAMecA PBP' (penicillin binding protein ')inhibitorStaphylococcus aureusAPenicillin-binding protein ANot AvailableClostridium perfringens (strain / Type A)UD-alanyl-D-alanine carboxypeptidase DacBNot AvailableEscherichia coli (strain K)UPenicillin acylaseNot AvailableLysinibacillus sphaericusUSolute carrier family member Not AvailableHumans",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Aza Compounds', 'Azabicyclo Compounds', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Sensitive Penicillins', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Natural Penicillins', 'Penicillin G', 'Penicillins', 'Sulfur Compounds']" +DB00713,Oxacillin,Oxacillinis a penicillin antibiotic used to treat a number of susceptible bacterial infections.,"['Q75Y35', 'Q8DNB6', 'Q8DR59', 'P0A3M6', 'Q7CRA4', 'Q8XJ01', 'P46059', 'D6R448', 'Q16348', 'Q47066']","Oxacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name ""penicillin"" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Oxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Oxacillin results from the inhibition of cell wall synthesis and is mediated through Oxacillin binding to penicillin binding proteins (PBPs). Oxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=CC=CC=C1)C(O)=O,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, Oxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Oxacillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)USolute carrier family member Not AvailableHumansUPenicillin-binding protein Not AvailableStaphylococcus aureusUSolute carrier family member Not AvailableHumansUBeta-lactamase Toho-substrateEscherichia coli",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Resistant Penicillins', 'beta-Lactams', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Sulfur Compounds']" +DB04821,Nomifensine,"Nomifensine, formerly marketed as Merital capsules, was associated with an increased incidence of hemolytic anemia. The approved application holder removed Merital capsules from the market on January 23, 1986. FDA published a notice of its determination that Merital capsules were removed from the market for safety reasons (see the Federal Register of June 17, 1986 (51 FR 21981)). Approval of the NDA for Merital capsules was withdrawn on March 20, 1992 (see the Federal Register of March 20, 1992 (57 FR 9729)). Also withdrawn from the Canadian and UK markets.","['P23975', 'Q01959', 'P27338', 'P21397', 'P05164', 'P31645', 'Q05940']","Nomifensine is a dopamine reuptake inhibitor test-marketed in the United States by Hoechst AG (now Novartis) that increases the amount of synaptic dopamine available to receptors by blocking dopamine's re-uptake transporter. Nomifensine is now mainly used in scientific research, particularly in studies involving dopamine release in response to addiction.",CN1CC(C2=CC=CC=C2)C2=C(C1)C(N)=CC=C2,TargetActionsOrganismUSodium-dependent noradrenaline transporterNot AvailableHumansUSodium-dependent dopamine transporterNot AvailableHumansUAmine oxidase [flavin-containing] BNot AvailableHumansUAmine oxidase [flavin-containing] ANot AvailableHumansUMyeloperoxidaseNot AvailableHumansUSodium-dependent serotonin transporterNot AvailableHumansUSynaptic vesicular amine transporterNot AvailableHumans,[],"['Antidepressive Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Psychoanaleptics']" +DB01405,Temafloxacin,"Temafloxacin is an antibiotic agent belonging to the fluoroquinolone drug class. It was first approved for use in the U.S. market in 1992, but was withdrawn shortly due to the reports of serious adverse reactions, such as allergic reactions and hemolyric anemia, resulting in three deaths.","['P43700', 'P43702']","Temafloxacin is a fluoroquinolone antibiotic drug, marketed as Omniflox by Abbot Laboratories, which was withdrawn from the market in 1992 due to fatal adverse effects. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such asE.coliandNeisseria gonorrhoeaas well as gram-positive bacteria includingS. pneumoniaeandStaphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.",CC1CN(CCN1)C1=C(F)C=C2C(=O)C(=CN(C2=C1)C1=C(F)C=C(F)C=C1)C(O)=O,"The bactericidal action of temafloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00339,Pyrazinamide,Pyrazinamideis an antituberculosis agent used as a component of tuberculosis (TB) treatment.,['P95029'],"Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only againstMycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.",NC(=O)C1=NC=CN=C1,"Pyrazinamide diffuses into activeM. tuberculosisthat express pyrazinamidase enzyme that converts pyrazinamide to the active form pyrazinoic acid. Pyrazinoic acid can leak out under acidic conditions to be converted to the protonated conjugate acid, which is readily diffused back into the bacilli and accumulate intracellularly. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted.However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids.This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I.It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria.TargetActionsOrganismAFatty acid synthetaseinhibitorMycobacterium tuberculosis (strain ATCC / HRv)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Drugs causing inadvertant photosensitivity', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Hepatotoxic Agents', 'Photosensitizing Agents', 'Pyrazines']" +DB00545,Pyridostigmine,Pyridostigmineis a cholinesterase inhibitor used for symptomatic treatment of myasthenia gravis and congenital myasthenic syndromes and to reverse neuromuscular blockade by nondepolarizing muscle relaxants.,"['P06276', 'P22303']","Pyridostigmine bromide, designated as 3-hydroxy-1-methyl-pyridinium bromide dimethyl-carbamate, is an orally active reversible cholinesterase inhibitor similar toneostigminebut with a milder adverse effect profile and a longer duration of action. Pyridostigmine may, specifically in the case of excessive administration, result in a cholinergic crisis, with symptoms mimicking a myasthenic crisis. Administration of atropine is recommended in the case of a true cholinergic crisis or to counteract muscarinic/nicotinic effects such as bradycardia and excessive bronchial secretions.10,11",CN(C)C(=O)OC1=C[N+](C)=CC=C1,"Myasthenia gravis is an autoimmune disease involving dysfunction at the neuromuscular junction most commonly due to autoantibodies directed against the acetylcholine receptor (AChR), but also against other targets such as the muscle-specific kinase (MUSK), lipoprotein-related protein (LRP), or agrin.In the case of AChR antibodies, AChRs are directly bound and cross-linked, impairing acetylcholine binding and contributing through various mechanisms to receptor degradation.The lack of acetylcholine signalling leads to muscle tone loss, muscle weakness, and fatigue.Pyridostigmine is a reversible acetylcholinesterase inhibitor that increases extracellular acetylcholine levels in the neuromuscular junction by impairing its breakdown by acetylcholinesterase.,The increased acetylcholine leads to increased neural transmission across the junction, which drastically improves myasthenia gravis symptoms.In addition to its use in myasthenia gravis and in reversing neuromuscular blocks, pyridostigmine is also a common first-line treatment in congenital myasthenic syndromes (CMS), of which there are multiple subtypes caused by mutations in more than distinct genes.,CMS present similarly to myasthenia gravis, albeit due to distinct underlying causes, and often benefit from pyridostigmine. However, in some subgroups, treatment with pyridostigmine is detrimental; detailed genetic testing is required before starting therapy.,TargetActionsOrganismACholinesteraseinhibitorHumansAAcetylcholinesteraseinhibitorHumans",[],"['Cholinergic Agents', 'Cholinesterase Inhibitors', 'Cholinesterase substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Enzyme Inhibitors', 'Nervous System', 'Neurotransmitter Agents', 'Parasympathomemetic (Cholinergic) Agents', 'Parasympathomimetics', 'Pyridines', 'Pyridinium Compounds']" +DB00168,Aspartame,"Flavoring agent sweeter than sugar, metabolized as phenylalanine and aspartic acid.","['Q7RTX0', 'Q8TE23', 'Q8NER1']","Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a low-calorie sweetener used to sweeten a wide variety of low- and reduced-calorie foods and beverages, including low-calorie tabletop sweeteners. Aspartame is composed of two amino acids, aspartic acid and phenylalanine, as the methyl ester. Aspartic acid and phenylalanine are also found naturally in protein containing foods, including meats, grains and dairy products. Methyl esters are also found naturally in many foods such as fruits and vegetable and their juices. Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood and used in normal body processes. Neither aspartame nor its components accumulates in the body. These components are used in the body in the same ways as when they are derived from common foods.",COC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CC(O)=O," to times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.TargetActionsOrganismUTaste receptor type member Not AvailableHumansUTaste receptor type member agonistHumansUTransient receptor potential cation channel subfamily V member inducerHumans",['Sweeteners'],"['Amino Acids, Peptides, and Proteins', 'Compounds used in a research, industrial, or household setting', 'Diet, Food, and Nutrition', 'Dietary Supplements', 'Dipeptides', 'Flavoring Agents', 'Food', 'Food Additives', 'Food Ingredients', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Oligopeptides', 'Peptides', 'Physiological Phenomena', 'Supplements', 'Sweetening Agents']" +DB00497,Oxycodone,Oxycodoneis an opioid used in the management of moderate to severe pain.,"['P35372', 'P41145', 'P41143']","Oxycodone acts directly on a number of tissues not related to its analgesic effect. These tissues include the respiratory centre in the brain stem, the cough centre in the medulla, muscles of the pupils, gastrointestinal tract, cardiovascular system, endocrine system, and immune system.LabelOxycodone's effect on the respiratory centre is dose dependant respiratory depression.LabelThe action on the cough centre is suppression of the cough reflex.LabelPupils become miopic or decrease in size, peristalsis of the gastrointestinal tract slows, and muscle tone in the colon may increase causing constipation.LabelIn the cardiovascular system histamine may be released leading to pruritis, red eyes, flushing, sweating, and decreased blood pressure.LabelEndocrine effects may include increased prolactin, decreased cortisol, and decreased testosterone.LabelIt is not yet known if the effects of opioids on the immune system are clinically significant.Label",COC1=C2O[C@H]3C(=O)CC[C@@]4(O)[C@H]5CC(C=C1)=C2[C@@]34CCN5C,"The full mechanism of oxycodone is not known.LabelUnder conditions of inflammation or hyperalgesia, opioid receptors in the heart, lungs, liver, gastrointestinal tract, and reproductive system are upregulated and transported to nerve terminals.Oxycodone and its active metabolites, noroxycodone, oxymorphone, and noroxymorphone are opioid agonists.These compounds passively diffuse across the blood brain barrier or may be actively transported across by an unknown mechanism.Oxycodone and its active metabolites can selectively bind to the mu opioid receptor, but also the kappa and delta opioid receptors in the central nervous system and periphery, and induce a G protein coupled receptor signalling pathway.Activation of mu opioid receptors inhibits N-type voltage operated calcium channels, inhibiting responses to pain.TargetActionsOrganismAMu-type opioid receptoragonistHumansAKappa-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumans",[],"['Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Natural Opium Alkaloids', 'Nervous System', 'Opiate Agonists', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Semi-synthetic Opioids', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00327,Hydromorphone,Hydromorphoneis an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.,"['P35372', 'P41143', 'P41145']","In clinical trials, hydromorphone has been shown to be suitable for pain relief in patients that do not tolerate the side effects ofmorphineor that suffer from renal failure or asthma. It has been shown to be 5-7 times more potent than morphine with a shorter duration of analgesia.2Some of the observed effects of the consumption of hydromorphone for acute pain are complete and longlasting pain relief when compared to other pain relief agents such asmeperidine,morphine,diamorphine,bupivacaine,indomethacin, andfentanyl. On the same trials, hydromorphone was shown to produce respiratory depression, lower cognitive function, miosis, mydriasis, constipation, hypotension, and vertigo but to present a reduced incidence of pruritus (which indicates a lower release of histamine) and nausea.7The respiratory depression is known to be caused by the effect on the brain stem respiratory centers as well as to a reduction in the responsiveness of this brain stems to increase carbon dioxide tension.10",[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CCC2=O,"Hydromorphone is an opioid agonist that can bind to different types of opioid receptors. Its analgesic effect is suggested to be related to the effect on the mu-opioid receptors. It has been reported to also have a minor affinity for the delta and kappa receptor.,On the other hand, it is known to act at the level of the medulla which allows it to depress the respiratory drive and suppress cough.The onset of action of the immediate release form of hydromorphone is achieved in - minutes and having a lasting effect for - hours while the extended-release form onset of action is of hours lasting for about hours.TargetActionsOrganismAMu-type opioid receptoragonistHumansADelta-type opioid receptorpartial agonistHumansAKappa-type opioid receptoragonistHumans",[],"['Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'High-risk opioids', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Natural Opium Alkaloids', 'Nervous System', 'Opiate Agonists', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Semi-synthetic Opioids', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB00844,Nalbuphine,"Nalbuphineis an opioid agonist-antagonist used to treat pain, for pre and postoperative analgesia, and for analgesia in labor and delivery.","['P41145', 'P35372', 'P41143']","Nalbuphine is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. Nalbuphine's analgesic potency is essentially equivalent to that ofmorphineon a milligram basis. The opoioid antagonist activity of nalbuphine is about one-fourth to that ofnalorphineand 10 times to that ofpentazocine. Nalbuphine by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. Nalbuphine may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.",O[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O5,"The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Nalbuphine is thought primarily to be a kappa agonist. It is also a partial mu antagonist analgesic, with some binding to the delta receptor and minimal agonist activity at the sigma receptor.TargetActionsOrganismAKappa-type opioid receptoragonistHumansAMu-type opioid receptorantagonistHumansADelta-type opioid receptorantagonistHumans","['Perioperative analgesia', 'Obstetric analgesia']","['Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Mixed Agonist / Antagonist Opioids', 'Morphinan Derivatives', 'Morphinans', 'Narcotics', 'Nervous System', 'Opiate Alkaloids', 'Opiate Partial Agonists', 'Opioid Agonist/Antagonist', 'Opioid Antagonists', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Semi-synthetic Opioids', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB02703,Fusidic acid,Fusidic acidis a topical antibacterial agent used to prevent and treat mild to moderate skin infections caused by susceptible bacteria.,"['P13551', 'P62580', 'P00484']",Fusidic acid is a bacteriostatic antibiotic and helps prevent bacterial growth while the immune system clears the infection.,[H][C@@]12C[C@@H](O)[C@@]3([H])[C@@]4(C)CC[C@@H](O)[C@@H](C)[C@]4([H])CC[C@]3(C)[C@@]1(C)C[C@H](OC(C)=O)\C2=C(\CCC=C(C)C)C(O)=O,"Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. It also can inhibit chloramphenicol acetyltransferase enzymes.TargetActionsOrganismAElongation factor GinhibitorThermus thermophilusUChloramphenicol acetyltransferaseinhibitorSalmonella typhiUChloramphenicol acetyltransferase inhibitorEscherichia coli",[],"['Agents Causing Muscle Toxicity', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives for Systemic Use', 'BCRP/ABCG2 Inhibitors', 'BSEP/ABCB11 Inhibitors', 'Cholestadienes', 'Cholestadienols', 'Cholestanes', 'Cholestenes', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Lipids', 'Medicated Dressings', 'Medicated Dressings With Antiinfectives', 'Membrane Lipids', 'OATP1B1/SLCO1B1 Inhibitors', 'Ophthalmologicals', 'Other Miscellaneous Antibacterial Agents', 'Protein Synthesis Inhibitors', 'Sensory Organs', 'Steroid Antibacterials', 'Steroids', 'Sterols', 'UGT1A1 Substrates']" +DB00114,Pyridoxal phosphate,Pyridoxal phosphateis a vitamin available in many formulations to correct vitamin B6 deficiency.,"['Q9BYV1', 'Q99259', 'P35520', 'Q16719', 'P34896', 'Q9Y697', 'P17174', 'P04181', 'P11926', 'Q8N5Z0', 'P80404', 'Q9NVS9', 'O95470', 'P17735', 'Q16773', 'P06737', 'O15270', 'Q9Y600', 'P19113', 'Q96A70', 'P20132', 'O75600', 'P23378', 'P24298', 'Q9Y617', 'P13196', 'P21549', 'Q96GD0', 'O15269', 'P32929', 'P54687', 'O15382', 'O94903', 'P00505', 'P11216', 'P11217', 'P20711', 'Q53ET4', 'Q59FK2', 'Q59GM9', 'Q5JAM2', 'Q5VZ30', 'Q6IBS8', 'Q6YP21', 'Q6ZQY3', 'Q96I15', 'Q6WRI0', 'Q8IUZ5', 'Q8IVA8', 'P34897', 'P22557', 'Q8TD30', 'Q96EN8', 'Q96GA7', 'Q9BXA1', 'Q9GZT4', 'Q9HD40', 'Q9NUV7', 'Q9UGI5', 'Q9UJX1', 'P17174', 'P00505']",The two major forms of vitamin B6 are pyridoxine and pyridoxamine. In the liver they are converted to pyridoxal phosphate (PLP) which is a cofactor in many reactions of amino acid metabolism. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen. Pyroluria is one potential cause of vitamin B6 deficiency.,CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O,"Pyridoxal Phosphate is a coenzyme of many enzymatic reactions. It is the active form of vitamin B which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine. Pyridoxal phosphate acts as a coenzyme in all transamination reactions, and in some +oxylation and deamination reactions of amino acids. The aldehyde group of pyridoxal phosphate forms a Schiff-base linkage with the epsilon-amino group of a specific lysine group of the aminotransferase enzyme. The alpha-amino group of the amino acid substrate displaces the epsilon-amino group of the active-site lysine residue. The resulting aldimine becomes deprotonated to become a quinoid intermediate, which in turn accepts a proton at a different position to become a ketimine. Ketimine becomes hydrolyzed so that the amino group remains on the protein complex.TargetActionsOrganismUAlanine--glyoxylate aminotransferase , mitochondrialcofactorHumansUGlutamate decarboxylase cofactorHumansUCystathionine beta-synthasecofactorHumansUKynureninasecofactorHumansUSerine hydroxymethyltransferase, cytosoliccofactorHumansUCysteine desulfurase, mitochondrialcofactorHumansUAspartate aminotransferase, cytoplasmicactivatorHumansUOrnithine aminotransferase, mitochondrialcofactorHumansUOrnithine decarboxylasecofactorHumansUKynurenine/alpha-aminoadipate aminotransferase, mitochondrialcofactorHumansU-aminobutyrate aminotransferase, mitochondrialinhibitorHumansUPyridoxine-'-phosphate oxidasecofactorHumansUSphingosine--phosphate lyase cofactorHumansUTyrosine aminotransferasecofactorHumansUKynurenine--oxoglutarate transaminase cofactorHumansUGlycogen phosphorylase, liver formcofactorHumansUSerine palmitoyltransferase cofactorHumansUCysteine sulfinic acid decarboxylasecofactorHumansUHistidine decarboxylasecofactorHumansUArginine decarboxylasecofactorHumansUL-serine dehydratase/L-threonine deaminasecofactorHumansU-amino--ketobutyrate coenzyme A ligase, mitochondrialcofactorHumansUGlycine dehydrogenase [decarboxylating], mitochondrialcofactorHumansUAlanine aminotransferase cofactorHumansUPhosphoserine aminotransferasecofactorHumansU-aminolevulinate synthase, nonspecific, mitochondrialcofactorHumansUSerine--pyruvate aminotransferasecofactorHumansUPyridoxal phosphate phosphatasecofactorHumansUSerine palmitoyltransferase cofactorHumansUCystathionine gamma-lyasecofactorHumansUBranched-chain-amino-acid aminotransferase, cytosoliccofactorHumansUBranched-chain-amino-acid aminotransferase, mitochondrialcofactorHumansUProline synthase co-transcribed bacterial homolog proteinbinderHumansUAspartate aminotransferase, mitochondrialcofactorHumansUGlycogen phosphorylase, brain formcofactorHumansUGlycogen phosphorylase, muscle formcofactorHumansUAromatic-L-amino-acid decarboxylasecofactorHumansUSerine hydroxymethyltransferasecofactorHumansUSelenocysteine lyase variantcofactorHumansUPhosphorylasecofactorHumansU-aminolevulinate synthasecofactorHumansUGlutamate decarboxylase (Pancreatic islets and brain, kDa)cofactorHumansUDDC proteincofactorHumansUKynurenine--oxoglutarate transaminase cofactorHumansUGlutamate decarboxylase-like protein cofactorHumansUSelenocysteine lyasecofactorHumansUImmunoglobulin superfamily member cofactorHumansU-phosphohydroxy-L-lysine phospho-lyasecofactorHumansUGlutamate decarboxylase (Brain, kDa)cofactorHumansUSerine hydroxymethyltransferase, mitochondrialcofactorHumansU-aminolevulinate synthase, erythroid-specific, mitochondrialcofactorHumansUAlanine aminotransferase cofactorHumansUMolybdenum cofactor sulfurasecofactorHumansUSerine dehydratase-likecofactorHumansUHepatic peroxysomal alanine:glyoxylate aminotransferasecofactorHumansUSerine racemasecofactorHumansUO-phosphoseryl-tRNA(Sec) selenium transferasecofactorHumansUSerine palmitoyltransferase cofactorHumansUGlutamic acid decarboxylasecofactorHumansUAlanine-glyoxylate aminotransferase homologcofactorHumansUAspartate aminotransferasecofactorHumans","['Folate supplementation therapy', 'Vitamin supplementation']","['Alimentary Tract and Metabolism', 'Coenzymes', 'Dietary Supplements', 'Enzymes and Coenzymes', 'Food', 'Micronutrients', 'Physiological Phenomena', 'Picolines', 'Pyridines', 'Supplements', 'Vitamin B Complex', 'Vitamins']" +DB00770,Alprostadil,Alprostadilis a prostaglandin E1 agonist used for the treatment of erectile dysfunction and as an adjunct for its diagnosis.,"['P34995', 'P43116', 'P43115', 'P35408', 'Q9Y5Y4']","Prostaglandin E1 is produced endogenously to relax vascular smooth muscle and cause vasodilation. As a synthetic form of prostaglandin E1, alprostadil has the same pharmacodynamic effects.1Alprostadil inhibits platelet aggregation, has anti-inflammatory effects, interferes with immune responses, and stimulates factor X, a blood coagulation enzyme.5In adult males, the use of alprostadil may lead to prolonged erection and priapism, penile fibrosis, hypotension, and injection site bleeding.6In patients treated up to 24 months with alprostadil, the incidence of prolonged erections (>4 hours long) was 4% of all, and the incidence of priapism (erections greater than 6 hours in duration) was <1%.7Patients with preexisting cardiovascular disease treated with alprostadil may also have higher cardiac risk.6Neonates with congenital heart defects treated with alprostadil may experience apnea. Apnea is experienced by 10-12% of neonates and is more common in those weighing less than 2 kg at birth. The administration of alprostadil to neonates may also result in gastric outlet obstruction secondary to antral hyperplasia.8",CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O,"Alprostadil is a smooth muscle relaxant that promotes vasodilation and platelet aggregation inhibition. In neonatal patients with ductus arteriosus patency, alprostadil relaxes the ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This results in increased pulmonary or systemic blood flow in infants. Alprostadil appears to be most effective within hours after birth since the DA rapidly loses its responsiveness to alprostadil.When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea leading to penile rigidity. This is referred to as the corporal veno-occlusive mechanism.,,TargetActionsOrganismAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumansUProstaglandin D receptor agonistHumans",[],"['Autacoids', 'Biological Factors', 'Cardiac Therapy', 'Cardiovascular Agents', 'Drugs Used in Erectile Dysfunction', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Monounsaturated', 'Fatty Acids, Unsaturated', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Genitourinary Arterial Vasodilation', 'Hematologic Agents', 'Inflammation Mediators', 'Lipids', 'Miscellaneous Vasodilatating Agents', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Substrates', 'OATP2B1/SLCO2B1 substrates', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Prostaglandin E1 Agonist', 'Prostaglandin Receptor Agonists', 'Prostaglandins', 'Prostaglandins E', 'Prostaglandins, Synthetic', 'Urological Agents', 'Urologicals', 'Vasodilating Agents', 'Venous Vasodilation']" +DB01452,Diamorphine,"Diamorphineis an opioid analgesic agent used in the relief of severe pain associated with surgical procedures, myocardial infarction or pain in the terminally ill and for the relief of dyspnea in acute pulmonary edema.","['P35372', 'P41145', 'P41143', 'P23141']","The onset of heroin's effects is dependent on the method of administration. Taken orally, heroin is totally metabolized in vivo via extensive first-pass metabolism into morphine before crossing the blood-brain barrier; so the effects are the same as orally administered morphine5,6. Take by injection, diamorphine's acetyl groups facilitate rapid crossing into the brain5,6. Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups, therefore making it a prodrug for the delivery of morphine5,6. Subsequently, whether eliciting actions peripherally (on smooth muscle, skeletal muscle, kidney, lung, liver, or spleen tissue5, for example) or on the central nervous system, it is ultimately the morphine metabolite of heroin that then binds with opioid receptors and produces the narcotic opioid effects commonly associated with the substance5,6.",[H][C@@]12C=C[C@H](OC(C)=O)[C@@H]3OC4=C(OC(C)=O)C=CC5=C4[C@]13CCN(C)[C@@H]2C5,"When administered orally, diamorphine experiences extensive first-pass metabolism by way of deacetylation to generate the active metabolites -monoacetylmorphine (-MAM) and morphine,. Alternatively, when given as an injection the acetyl groups present in the diamorphine/diacetylmorphine compound confer the substance lipophilicity that facilitates diamorphine's rapid crossing of the blood-brain-barrier,. Once in the brain, diamorphine is metabolised via deacetylation to the active -MAM and morphine metabolites as well,. Despite diamorphine possessing little to no opioid agonist activity itself, its rapid transit across the blood-brain-barrier elicits a far faster onset of activity in comparison to the extensive first-pass metabolism of oral administration,. Regardless, the metabolism of diamorphine to morphine makes heroin a prodrug for the delivery of morphine,.Morphine is subsequently a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Morphine, along with other opioids, are agonists to four endogenous neurotransmitters. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to morphine in the brain by reducing (and sometimes stopping) production of the endogenous opioids when morphine is present. Endorphins are regularly released in the brain and nerves, attenuating pain. Their other functions are still obscure, but are probably related to the effects produced by morphine besides analgesia (antitussin, anti-diarrheal).Nevertheless, morphine ultimately elicits the majority of its analgesic activity by binding to mu opioid receptors in both the central and peripheral nervous systems. The overall effect of morphine is activation of descending inhibitory pathways of the central nervous system as well as inhibition of nociceptive afferent neurons of the peripheral nervous system, which results in an overall reduction of the nociceptive pain transmission.TargetActionsOrganismAMu-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansULiver carboxylesterase Not AvailableHumans",[],"['Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs Used in Addictive Disorders', 'Drugs Used in Opioid Dependence', 'Heroin, agonists', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Nervous System', 'Opiate Agonists', 'Opiate Alkaloids', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Thyroxine-binding globulin inducers']" +DB01074,Perhexiline,Perhexiline is a coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis.,"['P50416', 'P23786', 'Q12809']","Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures.",C(C(C1CCCCC1)C1CCCCC1)C1CCCCN1,"Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)- and CPT-. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT- and, to a lesser extent, CPT-, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O consumption as before and consequently increases myocardial efficiency.TargetActionsOrganismACarnitine O-palmitoyltransferase , liver isoforminhibitorHumansACarnitine O-palmitoyltransferase , mitochondrialinhibitorHumansUPotassium voltage-gated channel subfamily H member Not AvailableHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Membrane Transport Modulators', 'Negative Inotrope', 'Non-Selective Calcium Channel Blockers', 'Piperidines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB00636,Clofibrate,Clofibrateis a fibric acid derivative used to treat hypertriglyceridemia and high cholesterol.,['Q07869'],"Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (Sf20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III hyperlipoproteinemia. Several investigators have observed in their studies that clofibrate may produce a decrease in cholesterol linoleate but an increase in palmitoleate and oleate, the latter being considered atherogenic in experimental animals. The significance of this finding is unknown at this time. Reduction of triglycerides in some patients treated with clofibrate or certain of its chemically and clinically similar analogs may be associated with an increase in LDL cholesterol. Increase in LDL cholesterol has been observed in patients whose cholesterol is initially normal. Animal studies suggest that clofibrate interrupts cholesterol biosynthesis prior to mevalonate formation.",CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1,"Clofibrate increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Clofibrate also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. Also, as a fibrate, Clofibrate is an agonist of the PPAR-α receptor[] in muscle, liver, and other tissues. This agonism ultimately leads to modification in gene expression resulting in increased beta-oxidation, decreased triglyceride secretion, increased HDL, increased lipoprotein lipase activity.TargetActionsOrganismAPeroxisome proliferator-activated receptor alphaagonistHumans",[],"['Acids, Acyclic', 'Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'Benzene Derivatives', 'Butyrates', 'Clofibric Acid', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ethers', 'Fibric Acids', 'Hypolipidemic Agents', 'Isobutyrates', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Phenols', 'Phenyl Ethers', 'Thyroxine-binding globulin inducers']" +DB00509,Dextrothyroxine,Dextrothyroxineis a thyroid hormone used to treat hyperlipidemia.,"['P10827', 'P10828', 'P07202']","Dextrothyroxine, the dextrorotary isomer of the synthetic thyroxine, is a antihyperlipidemic.",N[C@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O,"Dextrothyroxine is a antihyperlipidemic. The mechanism of action is not completely understood, but dextrothyroxine apparently acts in the liver to stimulate formation of low-density lipoprotein (LDL) and, to a much greater extent, to increase catabolism of LDL. This leads to increased excretion of cholesterol and bile acids via the biliary route into the feces, with a resulting reduction in serum cholesterol and LDL. Dextrothyroxine has no significant effect on high-density lipoproteins (HDL). +Inherently, it will also bind to thyroid receptors and as it is a prohormone, it will bind as a substrate to iodide peroxidase.TargetActionsOrganismAThyroid hormone receptor alphaagonistHumansAThyroid hormone receptor betaagonistHumansUThyroid peroxidaseNot AvailableHumans",[],"['Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain']" +DB01138,Sulfinpyrazone,Sulfinpyrazoneis a platelet inhibitory and uricosuric agent used to inhibit thrombotic and embolic processes and to manage the chronic phases of gout .,"['Q96S37', 'P33527', 'Q92887', 'O75469']","Sulfinpyrazone's pharmacologic activity is the potentiation of the urinary excretion of uric acid. It is useful for reducing the blood urate levels in patients with chronic tophaceous gout and acute intermittent gout, and for promoting the resorption of tophi.",O=C1C(CCS(=O)C2=CC=CC=C2)C(=O)N(N1C1=CC=CC=C1)C1=CC=CC=C1,"Sulfinpyrazone is an oral uricosuric agent (pyrazolone derivative) used to treat chronic or intermittent gouty arthritis. Sulfinpyrazone competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. This is likely done through inhibition of the urate anion transporter (hURAT) as well as the human organic anion transporter (hOAT). Sulfinpyrazone is not intended for the treatment of acute attacks because it lacks therapeutically useful analgesic and anti-inflammatory effects. Sulfinpyrazone and its sulfide metabolite possess COX inhibitory effects. Sulfinpyrazone has also been shown to be a UDP-glucuronsyltransferase inhibitor and a very potent CYPC inhibitor. Sulfinpyrazone is also known to be a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor as well as an inhibitor of several multridrug resistance proteins (MRPs).TargetActionsOrganismASolute carrier family member inhibitorHumansAMultidrug resistance-associated protein inhibitorHumansACanalicular multispecific organic anion transporter inhibitorHumansUNuclear receptor subfamily group I member activatorHumans",[],"['Antigout Preparations', 'Antiplatelet agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Musculo-Skeletal System', 'Preparations Increasing Uric Acid Excretion', 'Pyrazoles', 'Pyrazolones', 'Uricosuric Agents']" +DB00752,Tranylcypromine,Tranylcypromineis a monoamine oxidase inhibitor used to treat major depressive disorder.,"['P27338', 'P21397']","Tranylcypromine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. MAO is an enzyme that catalyzes the oxidative deamination of a number of amines, including serotonin, norepinephrine, epinephrine, and dopamine. Two isoforms of MAO, A and B, are found in the body. MAO-A is mainly found within cells located in the periphery and catalyzes the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine. MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine, is localized extracellularly and is found predominantly in the brain. While the mechanism of MAOIs is still unclear, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. It has been postulated that depression is caused by low levels of serotonin and/or norepinephrine and that increasing serotonergic and norepinephrinergic neurotransmission results in relief of depressive symptoms. MAO A inhibition is thought to be more relevant to antidepressant activity than MAO B inhibition. Selective MAO B inhibitors, such as selegiline, have no antidepressant effects.",NC1CC1C1=CC=CC=C1,"Tranylcypromine irreversibly and nonselectively inhibits monoamine oxidase (MAO). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms, as this results in an increase in the concentrations of these amines within the CNS.TargetActionsOrganismAAmine oxidase [flavin-containing] BinhibitorHumansAAmine oxidase [flavin-containing] AinhibitorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Amines', 'Anti-Anxiety Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Monoamine Oxidase Inhibitors, Non-Selective', 'Nervous System', 'Propylamines', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Tranquilizing Agents']" +DB00270,Isradipine,Isradipineis a dihydropyridine calcium channel blocker used for the treatment of hypertension.,"['Q13936', 'P54289', 'Q08289', 'O95180', 'Q9NY47', 'Q01668', 'Q13698']","Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.",COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC2=NON=C12)C(=O)OC(C)C,"Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels inHomo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha- subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Substrates', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Membrane Transport Modulators', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB08964,Gemeprost,"Gemeprostis a prostaglandin E1 analogue used for cervical dilation and, in combination with mifepristone, for pregnancy termination.","['P43115', 'P43116']",Gemeprost softens and dilates of the cervix prior to transcervical intrauterine operative procedures. It is a prostaglandin E1 analog that potently stimulates uterine contractions and causes cervical ripening and relaxation1.,CCCCC(C)(C)[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCC\C=C\C(=O)OC,"As a prostaglandin analog, gemeprost binds to prostaglandin E and E receptors as an agonist to cause myometrial contractions and progressive cervical dilation via tissue sensitization to oxytocin.TargetActionsOrganismAProstaglandin E receptor EP subtypeagonistHumansUProstaglandin E receptor EP subtypeagonistHumans","['Cervical Dilation', 'Pregnancy termination therapy']","['Abortifacient Agents', 'Abortifacient Agents, Nonsteroidal', 'Autacoids', 'Biological Factors', 'Drugs that are Mainly Renally Excreted', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Monounsaturated', 'Fatty Acids, Unsaturated', 'Genito Urinary System and Sex Hormones', 'Inflammation Mediators', 'Lipids', 'Prostaglandins', 'Prostaglandins E', 'Prostaglandins E, Synthetic', 'Reproductive Control Agents', 'Uterotonic agents']" +DB01580,Oxprenolol,"Oxprenololis a non-selective beta-adrenergic antagonist used to treat hypertension, angina pectoris, arrhythmias, and anxiety.","['P08588', 'P13945', 'P07550']","Oxprenolol is a non-selective beta blocker with some intrinsic sympathomimetic activity. Oxprenolol is a lipophilic molecule and hence, it is able to cross the blood-brain barrier. As such, it is associated with a higher incidence of CNS-related side effects than hydrophilic ligands such as atenolol, sotalol and nadolol. Oxprenolol is an potent beta-blocker and should not be administered to asthmatics because it can cause irreversible airway failure and inflammation.",CC(C)NCC(O)COC1=CC=CC=C1OCC=C,"Like other beta-adrenergic antagonists, oxprenolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, oxprenolol binds at beta()-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks beta- adrenergic receptors located in bronchiole smooth muscle, causing vasoconstriction. By binding beta- receptors in the juxtaglomerular apparatus, oxprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production. Oxprenolol therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorNot AvailableHumansUBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Anxiety Agents', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Autonomic Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Non-Selective', 'Beta Blocking Agents, Non-Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Negative Inotrope', 'Neurotransmitter Agents', 'OCT2 Inhibitors', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Sympatholytics', 'Tranquilizing Agents', 'Vasodilating Agents']" +DB04880,Enoximone,Enoximoneis a selective phosphodiesterase inhibitor indicated in the short term treatment of congestive heart failure.,['Q14432'],"Enoximone is a phosphodiesterase inhibitor (type III) that increases the force of contraction of the heart and dilates blood vessels. In June 2005, Myogen announced that they were discontinuing development of enoximone due to negative results. The drug is approved for use in the UK.",CSC1=CC=C(C=C1)C(=O)C1=C(C)NC(=O)N1,"Further research is required to determine accurately the mechanism of action of drugs with phosphodiesterase inhibitory activity, however, inhibition of PDE inhibits degredation of cGMP. This allows for increased NO release and vascular relaxation.TargetActionsOrganismAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumans",[],"['Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Imidazoles', 'Phosphodiesterase 3 Inhibitors', 'Phosphodiesterase Inhibitors', 'Photosensitizing Agents', 'Protective Agents', 'Vasodilating Agents']" +DB00401,Nisoldipine,Nisoldipineis a calcium channel blocker used as monotherapy or combined with other drugs for the treatment of hypertension.,"['Q13936', 'P54289', 'Q08289', 'Q01668', 'Q13698']","Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.",COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OCC(C)C,"By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nisoldipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Decreased Blood Pressure', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Membrane Transport Modulators', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Pyridines', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB01088,Iloprost,Iloprostis a synthetic prostacyclin analog indicated to treat pulmonary arterial hypertension (PAH).,"['P43119', 'P34995', 'P27815', 'Q07343', 'Q08493', 'Q08499', 'P00750', 'Q9Y5Y4']","Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. It was shown to affect platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer.",[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)C(C)CC#CC)[C@@]1([H])C\C(C2)=C\CCCC(O)=O,"Iloprost is a second generation structural analog of prostacyclin (PGI) with about ten-fold greater potency than the first generation stable analogs, such as carbaprostacyclin. Iloprost binds with equal affinity to human prostacyclin (Prostanoid IP) and prostaglandin EP receptors. Iloprost constricts the ilium and fundus circular smooth muscle as strongly as prostaglandin E (PGE) itself. Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets. In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time. All of these properties help to antagonize the pathological changes that take place in the small pulmonary arteries of patients with pulmonary hypertension.TargetActionsOrganismAProstacyclin receptoragonistHumansAProstaglandin E receptor EP subtypeagonistHumansUcAMP-specific ','-cyclic phosphodiesterase AinducerHumansUcAMP-specific ','-cyclic phosphodiesterase BinducerHumansUcAMP-specific ','-cyclic phosphodiesterase CinducerHumansUcAMP-specific ','-cyclic phosphodiesterase DinducerHumansUTissue-type plasminogen activatorother/unknownHumansUProstaglandin D receptor agonistHumans",[],"['Agents Causing Muscle Toxicity', 'Antiplatelet agents', 'Autacoids', 'Biological Factors', 'Blood and Blood Forming Organs', 'Cardiovascular Agents', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Hematologic Agents', 'Hypotensive Agents', 'Inflammation Mediators', 'Lipids', 'OATP2B1/SLCO2B1 substrates', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Prostacyclin Analogues', 'Prostaglandins', 'Prostaglandins, Synthetic', 'Vasodilating Agents']" +DB00852,Pseudoephedrine,"Pseudoephedrineis an alpha and beta adrenergic agonist used to treat nasal and sinus congestion, as well as allergic rhinitis.","['P23975', 'Q01959', 'P35348', 'P08913', 'P31645', 'P07550', 'P08588', 'O95644', 'P01375', 'P19838', 'P18846', 'P15336', 'P18847', 'P18848', 'Q9Y2D1', 'P18850', 'P17544', 'Q8WYK2', 'P01100', 'P05412', 'P60568']","Pseudoephedrine causes vasoconstriction which leads to a decongestant effect.2,12,13,14,15,16,17,18It has a short duration of action unless formulated as an extended release product.12,13,14,15,16,17,18Patients should be counselled regarding the risk of central nervous system stimulation.12,14,17,18",CN[C@@H](C)[C@@H](O)C1=CC=CC=C1,"Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptorsand less strongly as an agonist of beta adrenergic receptors.This agonism of adrenergic receptors produces vasoconstriction which is used as a decongestant,,,,,,,and as a treatment of priapism.Pseudoephedrine is also an inhibitor of norepinephrine, dopamine, and serotonin transporters.,The sympathomimetic effects of pseudoephedrine include an increase in mean arterial pressure, heart rate, and chronotropic response of the right atria.Pseudoephedrine is also a partial agonist of the anococcygeal muscle.Pseudoephedrine also inhibits NF-kappa-B, NFAT, and AP-.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent dopamine transporterinhibitorHumansAAlpha-A adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansASodium-dependent serotonin transporterinhibitorHumansUBeta- adrenergic receptorpartial agonistHumansUBeta- adrenergic receptoragonistpartial agonistHumansUNuclear factor of activated T-cells, cytoplasmic inhibitorHumansUTumor necrosis factorinhibitorHumansUNuclear factor NF-kappa-B p subunitinhibitorHumansUactivator protein inhibitorHumansUInterleukin-inhibitorHumans",['Airway secretion clearance therapy'],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Alpha-and Beta-adrenergic Agonists', 'Amines', 'Amino Alcohols', 'Amphetamines', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiovascular Agents', 'Ethylamines', 'Hyperglycemia-Associated Agents', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nasal Decongestants', 'Nasal Decongestants for Systemic Use', 'Nasal Preparations', 'Norepinephrine Releasing Agents', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Propanolamines', 'Propanols', 'Respiratory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetic (Adrenergic) Agents', 'Sympathomimetics', 'Tumor Necrosis Factor Blockers', 'Vasoconstrictor Agents']" +DB00243,Ranolazine,Ranolazineis an anti-anginal drug used for the treatment of chronic angina.,"['P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q07699', 'O60939', 'Q9NY72', 'Q8IWT1', 'Q14500', 'Q9UNX9', 'P63252', 'P48050', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'P35348', 'P35368', 'P25100', 'P08588']","Ranolazine exerts both antianginal and ischemic effects independent from lowering heart rate or blood pressure.9,17It blocks IKr, the rapid portion of the delayed rectifier potassium current, and prolongs the QTc interval in a dose-dependent fashion. The Ikr is important for cardiac repolarization.17Ranolazine exerts its therapeutic effects without negative chronotropic, dromotropic, or inotropic actions neither at rest, nor during exercise.1",COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1,"Myocardial ischemia exerts effects on adenosine triphosphate flux, leading to a decrease in the energy available for contraction and relaxation of the heart muscle. Electrolyte balance of sodium and potassium is necessary for maintaining normal cardiac contraction and relaxation. Disruption of adequate sodium and potassium electrolyte balance leads to excessively high concentrations of sodium and calcium, which likely interferes with oxygen supply to the heart muscle. This imbalance eventually leads to angina symptoms of chest pain or pressure, nausea, and dizziness, among others.,The mechanism of action for ranolazine is not fully understood. At therapeutic concentrations, it can inhibit the cardiac late sodium + current (INa), which may affect the electrolyte balance in the myocardium, relieving angina symptoms. The clinical significance this inhibition in the treatment of angina symptoms is not yet confirmed.Ranolazine inhibits sodium and potassium ion channel currents.It has been shown to exert weak activity on L-type calcium channels making it a weak direct vasodilator and exerts minimal direct effects on atrioventricular nodal conduction.Some additional mechanisms have been elucidated. Ranolazine exerts antagonistic activity towards the alpha and beta adrenergic receptors and inhibition of fatty acid oxidation.,TargetActionsOrganismUSodium channel proteininhibitorHumansUInward rectifier potassium channelinhibitorHumansUVoltage gated L-type calcium channelinhibitorHumansNAlpha- adrenergic receptorsantagonistHumansNBeta- adrenergic receptorantagonistHumansUFatty acidother/unknown",[],"['Acetamides', 'Antianginal Agents', 'BSEP/ABCB11 Substrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'MATE 1 Inhibitors', 'MATE 2 Inhibitors', 'MATE inhibitors', 'Membrane Transport Modulators', 'Miscellaneous Cardiac Drugs', 'Moderate Risk QTc-Prolonging Agents', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Piperazines', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Vasodilating Agents']" +DB01244,Bepridil,"A long-acting, non selective, calcium channel blocker with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. It is no longer marketed in the United States, as it has been implicated in causing ventricular arrhythmias (ie. Torsade de pointes).","['O00555', 'O95180', 'Q9NY47', 'P05023', 'P51787', 'P63316', 'P0DP23', 'Q01064', 'P54750', 'Q12809']","Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride.",CC(C)COCC(CN(CC1=CC=CC=C1)C1=CC=CC=C1)N1CCCC1,"Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytesin vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works.TargetActionsOrganismAVoltage-dependent P/Q-type calcium channel subunit alpha-AinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUSodium/potassium-transporting ATPase subunit alpha-inhibitorHumansUPotassium voltage-gated channel subfamily KQT member inhibitorHumansUTroponin C, slow skeletal and cardiac musclesotherHumansUCalmodulinbinderHumansUCalcium/calmodulin-dependent ','-cyclic nucleotide phosphodiesterase BinhibitorHumansUCalcium/calmodulin-dependent ','-cyclic nucleotide phosphodiesterase AinhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Highest Risk QTc-Prolonging Agents', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Non-Selective Calcium Channel Blockers', 'P-glycoprotein inhibitors', 'Phenylalkylamine Derivatives', 'Pyrrolidines', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB01240,Epoprostenol,Epoprostenolis a vasodilator and platelet aggregation inhibitor used for the management of primary pulmonary hypertension and pulmonary hypertension in patients with heart failure.,"['Q16647', 'Q9H244', 'P43119']","Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol.",[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)CCCCC)[C@@]1([H])C\C(O2)=C\CCCC(O)=O,"Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI and TXA work as physiological antagonists.TargetActionsOrganismAProstacyclin synthaseinducerHumansAPY purinoceptor agonistHumansAProstacyclin receptoragonistHumans",[],"['Anticoagulants', 'Antihypertensive Agents', 'Antiplatelet agents', 'Autacoids', 'Biological Factors', 'Blood and Blood Forming Organs', 'Cardiovascular Agents', 'Drugs that are Mainly Renally Excreted', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Hematologic Agents', 'Hypotensive Agents', 'Inflammation Mediators', 'Lipids', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Prostacyclin Analogues', 'Prostacycline Vasodilator', 'Prostaglandins', 'Prostaglandins I', 'Vasodilating Agents', 'Vasodilation']" +DB00598,Labetalol,"Labetalolis an alpha and beta adrenergic antagonist used to treat hypertension, angina, and sympathetic overactivity syndrome.","['P08588', 'P07550', 'P35348', 'P35368', 'P25100']","Labetalol antagonizes various adrenergic receptors to decrease blood pressure.5,3,4,7The duration of action is long as it is generally given twice daily, and the therapeutic window is wide as patients usually take 200-400mg twice daily.8Patients susceptible to bronchospasms should not use labetalol unless they are unresponsive to or intolerant of other antihypertensives.8",CC(CCC1=CC=CC=C1)NCC(O)C1=CC(C(N)=O)=C(O)C=C1,"Labetalol non-selectively antagonizes beta-adrenergic receptors, and selectively antagonizes alpha--adrenergic receptors.Following oral administration, labetalol has times the beta-blocking ability than alpha-blocking ability.This increases to . times following intravenous administration.Antagonism of alpha--adrenergic receptors leads to vasodilation and decreased vascular resistance.This leads to a decrease in blood pressure that is most pronounced while standing.Antagonism of beta--adrenergic receptors leads to a slight decrease in heart rate.Antagonism of beta--adrenergic receptors leads to some of the side effects of labetalol such as bronchospasms, however this may be slightly attenuated by alpha--adrenergic antagonism.Labetalol leads to sustained vasodilation over the long term without a significant decrease in cardiac output or stroke volume, and a minimal decrease in heart rate.,TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumansAAlpha- adrenergic receptorsantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Agents producing tachycardia', 'Alcohols', 'Alpha and Beta Blocking Agents', 'Alpha and Beta Blocking Agents and Thiazides', 'Amides', 'Amines', 'Amino Alcohols', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Beta Blocking Agents and Thiazides', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Ethanolamines', 'Hypotensive Agents', 'Negative Inotrope', 'Neurotransmitter Agents', 'Peripheral alpha-1 blockers', 'Peripheral Nervous System Agents', 'Salicylamides', 'Sympathomimetics', 'UGT1A1 Substrates', 'UGT1A9 Substrates', 'UGT2B7 substrates', 'Vasodilating Agents']" +DB00692,Phentolamine,"Phentolamineis an alpha-adrenergic blocker used to treat hypertensive episodes, diagnose pheochromocytoma, treat norepinephrine administration site reactions, and reverse soft tissue anesthesia and mydriasis.","['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'Q14654']","Phentolamine produces an alpha-adrenergic block of a relatively short duration.7Phentolamine induces vasodilatation of vascular smooth muscle and pupils.7,5When used in an ophthalmic solution, the onset of pupil dilation generally occurred in 30 minutes, with the maximal effect seen in 60 to 90 minutes. Pupil dilation lasted for at least 24 hours.5Phentolamine also has direct but less marked positive inotropic and chronotropic effects on cardiac muscle and vasodilator effects on vascular smooth muscle;8however, phentolamine is not believed to affect contractile or adenyl cyclase function.1Large doses can lead to a mild sympatholytic action.1Some evidence suggests that phentolamine also stimulates beta-adrenergic receptors, thereby causing peripheral vasodilation.1Phentolamine was shown to stimulate insulin secretion, possibly related to its blocking actions on ATP-sensitive K+channels.1,3",CC1=CC=C(C=C1)N(CC1=NCCN1)C1=CC(O)=CC=C1,"Phentolamine is a reversible, competitive antagonist at alpha- and alpha- adrenergic receptors.,It causes vasodilation of vascular smooth muscles.Pupil dilation is primarily controlled by the radial iris dilator muscles surrounding the pupil, which are activated by the alpha- adrenergic receptors. Phentolamine reversibly binds to these receptors and reduces pupil diameter. By blocking alpha- adrenergic receptors, phentolamine can also be used to reverse mydriasis induced by muscarinic antagonists.TargetActionsOrganismAAlpha- adrenergic receptorsantagonistHumansUAlpha- adrenergic receptorsantagonistHumansUATP-sensitive inward rectifier potassium channel blockerHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidotes', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Imidazoles', 'Imidazoline Derivatives', 'Neurotransmitter Agents', 'Non-selective Alfa-adrenergic Blocking Agents', 'Peripheral alpha-1 blockers', 'Peripheral Vasodilators', 'Sympatholytic (Adrenergic Blocking) Agents', 'Vasodilating Agents']" +DB01095,Fluvastatin,Fluvastatinis an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke.,"['P04035', 'Q92769']","Fluvastatin, the first synthetically-derived HMG-CoA reductase inhibitor, is a hydrophilic, acidic, antilipemic agent used to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb), to slow the progression of coronary atherosclerosis in patients with CHD and as secondary prevention therapy in patients with CHD to reduce the risk of requiring coronary revascularization procedures. Although similar to lovastatin, simvastatin, and pravastatin, fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Fluvastatin acts primarily in the liver. It is prepared as a racemate of two erythro enantiomers of which the 3R,5S enantiomer exerts the pharmacologic effect.",CC(C)N1C(\C=C\C(O)CC(O)CC(O)=O)=C(C2=CC=CC=C12)C1=CC=C(F)C=C1,"Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUHistone deacetylase inhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fatty Acids', 'Heptanoic Acids', 'Heterocyclic Compounds, Fused-Ring', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Indoles', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Lipids', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB06709,Methacholine,Methacholineis a parasympathomimetic bronchoconstrictor used to diagnose bronchial hyperreactivity in subjects who do not have clinically apparent asthma.,"['P20309', 'P08172', 'P11229', 'P08173', 'P08912']","Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction, which is more significant in patients with asthma than those without. Therefore, methacholine carries a risk of severe bronchoconstriction, especially in patients with pre-existing reduced pulmonary function (typically baseline FEV1< 60% or < 1.5 L, at least in adults), clinically apparent asthma or wheezing, or other health conditions such as uncontrolled hypertension, aortic aneurysm, or history of myocardial infarction or stroke. Use in patients with epilepsy, vagotonia, peptic ulcer disease, thyroid disease, urinary tract obstruction or other conditions that could be adversely affected by a cholinergic agent is not recommended. Also, there is a potential risk to healthcare workers administering the methacholine challenge test; proper precautions and protective equipment should be used as needed.11",CC(C[N+](C)(C)C)OC(C)=O,"Asthma is a complicated condition associated with airway remodelling, including the proliferation of airway smooth muscle (ASM) and altered extracellular matrix, aberrant pro-inflammatory immune responses, and excessive ASM contraction leading to decreased lung function.,Excessive ASM contraction in response to contractile agonists, a phenomenon termed airway hyperresponsiveness (AHR), is a physical manifestation of the altered pulmonary physiology in asthma.Although numerous factors, such as increased ASM levels, pro-contractile molecules, pro-inflammatory cytokines, and growth factors, contribute to AHR, one of the key factors in determining ASM tone is regulated by vagal parasympathetic nerve innervation.,,The response to acetylcholine and other cholinergic agonists at these neuromuscular junctions is predominantly controlled by inhibitory Gi-coupled Mand excitatory Gq-coupled Mmuscarinic acetylcholine receptors (mAChRs). Activation of Mreceptors results in ASM contraction and resulting bronchoconstriction through downstream calcium-dependent signalling pathways, while Mactivation inhibits neuronal acetylcholine release.,,Methacholine is a non-specific mAChR agonist, capable of acting on all mAChR subtypes.,,However, in the context of AHR, methacholine's ability to induce bronchoconstriction through Mreceptors is clinically relevant.,,In addition, Magonism may increase the release of pro-inflammatory cytokines, further contributing to AHR.The inhibitory effect of Magonism by methacholine is likely also important, as shown by animal studies using mice with impaired Mfunction, and by observations that eosinophilic inflammation, such as occurs in asthma, negatively impacts Mfunction.Hence, asthmatic patients are more sensitive to inhaled cholinergic agonists such as methacholine; this forms the basis for the methacholine challenge test, which diagnoses AHR through an increased methacholine-induced response.,TargetActionsOrganismAMuscarinic acetylcholine receptor MagonistHumansAMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumans",[],"['Amines', 'Ammonium Compounds', 'Autonomic Agents', 'Bronchoconstrictor Agents', 'Cholinergic Agents', 'Cholinergic Agonists', 'Cholinergic Receptor Agonist', 'Diagnostic Agents', 'Methacholine Compounds', 'Miotics', 'Muscarinic Agonists', 'Neurotransmitter Agents', 'Nitrogen Compounds', 'Onium Compounds', 'Other Diagnostics', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds', 'Respiratory System Agents', 'Trimethyl Ammonium Compounds']" +DB00696,Ergotamine,Ergotamineis an alpha-1 selective adrenergic agonist vasoconstrictor used to treat migraines with or without aura and cluster headaches.,"['P28221', 'P28222', 'P28223', 'P35348', 'P35368', 'P25100', 'P14416', 'P08913', 'P21728', 'P21918', 'P08908', 'P30939', 'P28335', 'P41595', 'P18825']","Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow.",[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)C4=C3)O[C@@]21O,"Ergotamine acts on migraine by one of two proposed mechanisms: ) activation of -HTDreceptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache, and ) activation of -HTDreceptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.TargetActionsOrganismA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor AagonistHumansAAlpha-A adrenergic receptorpartial agonistHumansAAlpha-B adrenergic receptorpartial agonistHumansAAlpha-D adrenergic receptorpartial agonistHumansUDopamine D receptoragonistHumansUAlpha-A adrenergic receptorpartial agonistHumansUD() dopamine receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor FagonistHumansU-hydroxytryptamine receptor CagonistHumansU-hydroxytryptamine receptor BNot AvailableHumansUAlpha-C adrenergic receptorNot AvailableHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Alkaloids', 'Analgesics', 'Analgesics, Non-Narcotic', 'Antidepressive Agents', 'Antimigraine Preparations', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ergot Alkaloids and Derivatives', 'Ergotamine Derivative', 'Ergotamines', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Reproductive Control Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Sympatholytic (Adrenergic Blocking) Agents', 'Uterotonic agents', 'Vasoconstrictor Agents']" +DB00669,Sumatriptan,Sumatriptanis a serotonin receptor agonist used to treat migraines and cluster headaches.,"['P08908', 'P28221', 'P28222', 'P30939']","Sumatriptan constricts cranial blood vessels and prevents the release of vasoactive peptides.2The dose of sumatriptan varies widely by route of administration and in most cases, no more than 2 doses should be given daily.5,6,7,8,9,10Medication overuse headaches may occur in patients who use sumatriptan frequently.5,6,7,8,9,10",CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1,"Sumatriptan is an agonist of -HTBand -HTD.,,,,,This agonism leads to constriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides.,,,,,Sumatriptan decreases carotid arterial blood flow, but increases blood flow velocity in the internal carotid artery and middle cerebral artery.,,TargetActionsOrganismA-hydroxytryptamine receptor AagonistHumansA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor FagonistHumans",[],"['Agents that produce hypertension', 'Amides', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'BCRP/ABCG2 Substrates', 'Biogenic Amines', 'Biogenic Monoamines', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Monoamine Oxidase A Substrates', 'Nervous System', 'Neurotransmitter Agents', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein substrates', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Triptans', 'Tryptamines', 'Vasoconstrictor Agents']" +DB01023,Felodipine,Felodipineis a calcium channel blocker used to treat hypertension.,"['Q13936', 'P54289', 'Q08289', 'Q01668', 'Q13698', 'O95180', 'Q9NY47', 'P0DP23', 'Q01064', 'P54750', 'P08235', 'P02585', 'P63316']","Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.",CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC,"Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansUVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUCalmodulinotherHumansUCalcium/calmodulin-dependent ','-cyclic nucleotide phosphodiesterase BinhibitorHumansUCalcium/calmodulin-dependent ','-cyclic nucleotide phosphodiesterase AinhibitorHumansUMineralocorticoid receptorantagonistHumansUTroponin C, skeletal muscleotherHumansUTroponin C, slow skeletal and cardiac musclesotherHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Beta blocking agents and calcium channel blockers', 'Bradycardia-Causing Agents', 'BSEP/ABCB11 Substrates', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB09242,Moxonidine,"Moxonidineis an imidazoline/α-2 receptor agonist used to treat hypertension, especially in cases where ACE inhibitors, β-blockers, calcium channel blockers, and thiazides are not appropriate or provide inadequate blood pressure control.","['P08913', 'Q9Y2I1']","Antihypertensive agent whose site of action is the Central Nervous System (CNS), specifically involving interactions with I1- imidazoline and alpha-2-adrenergic rececptors within the rostral ventrolateral medulla (RSV).Label",COC1=NC(C)=NC(Cl)=C1NC1=NCCN1,"Stimulation of central alpha -adrenergic receptors is associated with sympathoadrenal suppression and subsequent reduction of blood pressure. As this class was further explored it was discovered that sympathoadrenal activity can also be suppressed by a second pathway with a newly discovered drug target specific to imidazolines. Specifically, moxonidine binds the imidazoline receptor subtype (I) and to a lesser extent αlpha--adrenoreceptors in the RSV causing a reduction of sympathetic activity, reducing systemic vascular resistance and thus arterial blood pressure.LabelMoreover, since alpha--adrenergic receptors are considered the primary molecular target that facilitates the most common side effects of sedation and dry mouth that are elicited by most centrally acting antihypertensives, moxonidine differs from these other centrally acting antihypertensives by demonstrating only low affinity for central alpha--adrenoceptors compared to the aforementioned I-imidazoline receptorsLabel.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansANischarinagonistHumans",[],"['Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Antiadrenergic Agents, Centrally Acting', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Hypotensive Agents', 'Imidazoline Receptor Agonists', 'Sympatholytics']" +DB01193,Acebutolol,Acebutololis a selective β1-receptor antagonist used for the management of hypertension and ventricular premature beats in adults.,"['P08588', 'P07550']","Acebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. In general, beta-blockers reduce the work the heart has to do and allow it to beat more regularly. Acebutolol has less antagonistic effects on peripheral vascular ß2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists. Low doses of acebutolol produce less evidence of bronchoconstriction than nonselective agents like propranolol but more than atenolol.",CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(=C1)C(C)=O,"Acebutolol is a selective β-receptor antagonist. Activation of β-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Acebutolol blocks these receptors, lowering the heart rate and blood pressure. This drug then has the reverse effect of epinephrine. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.TargetActionsOrganismABeta- adrenergic receptorpartial agonistHumansUBeta- adrenergic receptorpartial agonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Selective', 'Beta Blocking Agents, Selective, and Thiazides', 'Beta-Blockers (Beta1 Selective)', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Sympathomimetics']" +DB01268,Sunitinib,Sunitinibis a receptor tyrosine kinase inhibitor and chemotherapeutic agent used for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST).,"['P09619', 'P17948', 'P10721', 'P35968', 'P35916', 'P36888', 'P07333', 'P16234', 'P08581']","Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.",CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C,"Sunitinib is a small molecule that inhibits multiple RTKs, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (> kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR, VEGFR and VEGFR), stem cell factor receptor (KIT), Fms-like tyrosine kinase- (FLT), colony stimulating factor receptor Type (CSF-R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.TargetActionsOrganismAPlatelet-derived growth factor receptor betainhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAMast/stem cell growth factor receptor KitinhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAReceptor-type tyrosine-protein kinase FLTinhibitorHumansAMacrophage colony-stimulating factor receptorinhibitorHumansAPlatelet-derived growth factor receptor alphainhibitorHumansUHepatocyte growth factor receptorinhibitorHumans",[],"['Angiogenesis Inhibitors', 'Angiogenesis Modulating Agents', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Growth Inhibitors', 'Growth Substances', 'Hepatotoxic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hypoglycemia-Associated Agents', 'Immunosuppressive Agents', 'Indoles', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Tyrosine Kinase Inhibitors']" +DB00195,Betaxolol,Betaxololis a cardioselective beta blocking agent commonly used to treat hypertension and elevated intraocular pressure (when administered ophthalmically).,"['P08588', 'P07550']","Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, beta(1)-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.",CC(C)NCC(O)COC1=CC=C(CCOCC2CC2)C=C1,"Betaxolol selectively blocks catecholamine stimulation of beta()-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. Betaxolol can also competitively block beta()-adrenergic responses in the bronchial and vascular smooth muscles, causing bronchospasm.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Beta Blocking Agents, Selective', 'Beta-adrenergic Agents', 'Beta-Blockers (Beta1 Selective)', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Sensory Organs', 'Sympatholytics']" +DB01020,Isosorbide mononitrate,Isosorbide mononitrateis a nitrate used to prevent and treat angina and to treat angina caused by coronary artery disease.,['P33402'],"Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. The pharmacological action is mediated by the active metabolite,nitric oxide, which is released when isosorbide mononitrate is metabolized.3Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload.7In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness.3At therapeutic doses of isosorbide mononitrate, nitric oxide has a bigger effect on larger muscular arteries over small resistance arteries. Arterial relaxation leads to reduced systemic vascular resistance and systolic blood (aortic) pressure, decreasing to decreased cardiac afterload.7,3The direct dilator effect on coronary arteries opposes the coronary artery spasm in variant angina or angina pectoris.3At larger doses, nitric oxide causes the resistance arteries and arterioles to dilate, reducing arterial pressure via coronary vasodilatation. This leads to increased coronary blood flow.7,3Reduced cardiac preload and afterload caused by nitric oxide causes a reduction in myocardial oxygen consumption; decreased myocardial oxygen demand, along with increased coronary blood flow, leads to an increased in the oxygen content of coronary sinus blood3and the relief from ischemia.7The end effect of isosorbide mononitrate include decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms. Nitric oxide can also increase the rate of relaxation of cardiac muscles, which is an effect outside of vascular smooth muscles.3Organic nitrates can also relax other types of smooth muscles, including esophageal and biliary smooth muscle.3The anti-anginal activity of isosorbide mononitrate was observed about 1 hour after dosing, and the peak effect was achieved from 1-4 hours after dosing.4The duration of anti-anginal action of at least 12 hours was observed with an asymmetrical dosing regimen.2",[H][C@]12OC[C@@H](O[N+]([O-])=O)[C@@]1([H])OC[C@@H]2O,"Isosorbide mononitrate acts as a prodrug for nitric oxide (NO), which is a potent vasodilator gas that is released when the drug is metabolized. NO activates soluble guanylyl cyclase in vascular endothelial cells, which increases the intracellular concentrations of cyclic GMP (cGMP). cGMP activates cGMP-dependent protein kinases, such as protein kinase G and I, which activates the downstream intracellular cascades.The downstream cascade results in reduced intracellular concentrations of calcium, caused by processes including inhibition of IP-mediated pathway, phosphorylation of big calcium-activated potassium channel leading to cell hyperpolarization and reduced calcium influx, and increased calcium efflux via the Ca+-ATPase-pump.Reduced intracellular calcium concentrations lead to the dephosphorylation of myosin light chains and the relaxation of smooth muscle cells.,TargetActionsOrganismAGuanylate cyclase soluble subunit alpha-activatorHumans",[],"['Alcohols', 'Antianginal Agents', 'Carbohydrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Delayed-Action Preparations', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Methemoglobinemia Associated Agents', 'Nitrate Vasodilator', 'Nitrates and Nitrites', 'Nitric Oxide Donors', 'Organic Nitrates', 'Sugar Alcohols', 'Vasodilating Agents', 'Vasodilation', 'Vasodilators Used in Cardiac Diseases']" +DB00612,Bisoprolol,Bisoprololis a beta-1 adrenergic blocking agent used to prevent myocardial infarction and heart failure and to treat mild to moderate hypertension.,"['P08588', 'P07550']","Bisoprolol decreases heart rate (chronotropy), decreases contractility (inotropy), and reduces blood pressure.15,17The results of various clinical studies indicate that bisoprolol reduces cardiovascular mortality and all-cause mortality in patients with heart failure and decreased cardiac ejection fraction (EF).3,8",CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1,"Though the mechanism of action of bisoprolol has not been fully elucidated in hypertension, it is thought that therapeutic effects are achieved through the antagonism of β-adrenoceptors to result in lower cardiac output. Bisoprolol is a competitive, cardioselective β-adrenergic antagonist. When β-receptors (located mainly in the heart)are activated by adrenergic neurotransmitters such as epinephrine, both the blood pressure and heart rate increase, leading to greater cardiovascular work, increasing the demand for oxygen. Bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen through competitive inhibition of β-adrenergic receptors.,Bisoprolol is also thought to reduce the output of renin in the kidneys, which normally increases blood pressure. Additionally, some central nervous system effects of bisoprolol may include diminishing sympathetic nervous system output from the brain, decreasing blood pressure and heart rate.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansNBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Beta blocking agents and calcium channel blockers', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Selective', 'Beta Blocking Agents, Selective, and Thiazides', 'Beta-Blockers (Beta1 Selective)', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'Sympatholytics']" +DB09069,Trimetazidine,Trimetazidineis a piperazine derivative indicated as an adjunct therapy in symptomatic treatment of stable angina pectoris.,['P42765'],"Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies.9Patients should be counselled regarding the risk of use with reduced renal or hepatic function, worsening of extrapyramidal symptoms or other movement disorders, and risk of falls.10",COC1=C(OC)C(OC)=C(CN2CCNCC2)C=C1,"During myocardial ischemia, anaerobic metabolism takes over, increasing levels of lactic acid.The decreased intracellular pH and increased concentration of protons activates sodium-hydrogen and sodium-calcium antiport systems, raising intracellular calcium concentrations, finally leading to decreased contractility.This injury to the myocardium raises concentrations of catecholamines, which activate hormone sensitive lipase, and increasing fatty acid concentrations in plasma.When the myocardium is repurfused, fatty acid oxidation becomes the dominant form of ATP production, maintaining an acidic pH, and further exacerbating the injury.The mechanism of action of trimetazidine is not fully understood.Trimetazidine may inhibit mitochondrial -ketoacyl coenzyme A thiolase, decreasing long chain fatty acid β-oxidation but not glycolysis in the myocardium.,The decreased long chain fatty acid β-oxidation is compensated for by increased use of glucose, preventing a lowered myocardial pH, and further decreases in contractility.,However, another study suggests that -ketoacyl coenzyme A thiolase may not be trimetazidine's target, and that this mechanism may be incorrect.TargetActionsOrganismU-ketoacyl-CoA thiolase, mitochondrialinhibitorHumans",[],"['Cardiac Therapy', 'Cardiovascular Agents', 'Piperazines', 'Vasodilating Agents']" +DB00866,Alprenolol,"One of the adrenergic beta-antagonists used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. Alprenolol is no longer marketed by AstraZeneca, but may still be available in generic varieties.","['P08588', 'P07550', 'P08908', 'P13945']","Alprenolol is a non-selective beta-blocker used in the treatment of hypertension, edema, ventricular tachycardias, and atrial fibrillation. Alprenolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Alprenolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Alprenolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, alprenolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.",CC(C)NCC(O)COC1=CC=CC=C1CC=C,"Alprenolol non-selectively blocks beta- adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. Also, with a more minor effect, by binding beta- receptors in the juxtaglomerular apparatus, alprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansUBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antidepressive Agents', 'Antihypertensive Agents', 'Autonomic Agents', 'Beta Blocking Agents, Non-Selective', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sympatholytics']" +DB00988,Dopamine,"Dopamineis a catecholamine neurotransmitter used to treat hemodynamic imbalances, poor perfusion of vital organs, low cardiac output, and hypotension.","['P14416', 'P21728', 'P21918', 'P35462', 'P21917', 'Q01959', 'P09172', 'P08908', 'P34969', 'P21728', 'P21918', 'P23975', 'P31645', 'P46098', 'O95264', 'P00441', 'Q05940']","Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings.",NCCC1=CC(O)=C(O)C=C1,"Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings. In the brain, dopamine acts as an agonist to the five dopamine receptor subtypes (D, D, D, D, D).TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansASodium-dependent dopamine transporterinducerHumansADopamine beta-hydroxylaseligandHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor binderHumansUD() dopamine receptoragonistHumansUSodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent serotonin transporterinhibitorHumansU-hydroxytryptamine receptor ANot AvailableHumansU-hydroxytryptamine receptor BNot AvailableHumansUSuperoxide dismutase [Cu-Zn]Not AvailableHumansUSynaptic vesicular amine transporterNot AvailableHumans",[],"['Adrenergic and Dopaminergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Autonomic Agents', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'Compounds used in a research, industrial, or household setting', 'COMT Substrates', 'Dopamine Agents', 'Dopamine, metabolism', 'Drugs that are Mainly Renally Excreted', 'Monoamine Oxidase A Substrates', 'Neurotransmitter Agents', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Peripheral Nervous System Agents', 'Phenols', 'Protective Agents', 'Selective Beta 1-adrenergic Agonists', 'Sympathomimetics']" +DB00610,Metaraminol,An adrenergic agonist that acts predominantly at alpha adrenergic receptors and also stimulates the release of norepinephrine. It has been used primarily as a vasoconstrictor in the treatment of hypotension.,['P35348'],"Metaraminol is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Metaraminol is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Metaraminol acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels.",C[C@H](N)[C@H](O)C1=CC(O)=CC=C1,"Metaraminol acts through peripheral vasoconstriction by acting as a pure alpha- adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic & diastolic). Its effect is thought to be associated with the inhibition of adenyl cyclase which leads to an inhibition of the production of cAMP. Another effect of Metaraminol is that it releases norepinephrine from its storage sites indirectly.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Autonomic Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Propanolamines', 'Propanols', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB00353,Methylergometrine,Methylergometrineis an ergot alkaloid used to prevent and control uterine atony and hemorrhage before and after delivery.,"['P21728', 'P41595']","Methylergometrine is a semisynthetic ergot alkaloid and a derivative of ergonovine and is used for the prevention and control of postpartum and post-abortion hemorrhage. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result.",[H][C@@]12CC3=CNC4=CC=CC(=C34)C1=C[C@H](CN2C)C(=O)N[C@@H](CC)CO,"Methylergometrine acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions through binding and the resultant antagonism of the dopamine D receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss.TargetActionsOrganismADopamine D receptorantagonistHumansU-hydroxytryptamine receptor BNot AvailableHumans",[],"['Agents that produce hypertension', 'Alkaloids', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Ergolines', 'Ergonovine', 'Ergot Alkaloids and Derivatives', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Reproductive Control Agents', 'Uterotonic agents']" +DB00465,Ketorolac,"Ketorolacis an NSAID used to treat moderate to severe pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders, and headaches.","['P35354', 'P23219']","Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever.As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme.3Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations.7",OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1,"Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action.Although ketorolac is non-selective and inhibits both COX- and COX- enzymes, it's clinical efficacy is derived from it's COX- inhibition. The COX- enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation.Ketorolac is administered as a racemic mixture; however, the ""S"" enantiomer is largely responsible for it's pharmacological activity.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Musculo-Skeletal System', 'Mydriatics', 'Mydriatics and Cycloplegics', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Ophthalmologicals', 'Other Nonsteroidal Anti-inflammatory Agents', 'Photosensitizing Agents', 'Sensory Organs', 'Sympathomimetics Excl. Antiglaucoma Preparations', 'UGT2B7 substrates']" +DB01009,Ketoprofen,"Ketoprofenis an NSAID used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, dysmenorrhea, mild to moderate muscle pain, postoperative pain, and postpartum pain.","['P35354', 'P23219', 'P25024']","Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties. Ketoprofen has pharmacologic actions similar to those of other prototypical NSAIDs, which inhibit prostaglandin synthesis. Ketoprofen is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and alleviate moderate pain.",CC(C(O)=O)C1=CC(=CC=C1)C(=O)C1=CC=CC=C1,"The anti-inflammatory effects of ketoprofen are believed to be due to inhibition cylooxygenase- (COX-), an enzyme involved in prostaglandin synthesis via the arachidonic acid pathway. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation. Ketoprofen is a non-specific cyclooxygenase inhibitor and inhibition of COX- is thought to confer some of its side effects, such as GI upset and ulceration. Ketoprofen is thought to have anti-bradykinin activity, as well as lysosomal membrane-stabilizing action. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumansUC-X-C chemokine receptor type otherHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amino Acids', 'Amino Acids, Basic', 'Amino Acids, Diamino', 'Amino Acids, Peptides, and Proteins', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Phenylpropionates', 'Photosensitizing Agents', 'Propionates', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain', 'UGT1A1 Substrates']" +DB00630,Alendronic acid,Alendronic acidis a bisphosphonate drug that prevents osteoclastic bone resorption which is used for the prevention and treatment of osteoporosis.,"['P14324', 'P29074', 'Q13332', 'P23469', 'P38606']",Alendronic acid tablets have a very low oral bioavialabilityLabel2. After administration it distributes into soft tissue and bone or is excreted in the urineLabel. Alendronic acid does not undergo metabolismLabel.,NCCCC(O)(P(O)(O)=O)P(O)(O)=O,"Alendronic acid binds to bone hydroxyapatiteLabel. Bone resorption causes local acidification, releasing alendronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing alendronic acid to the cytosol of osteoclasts where they induce apoptosis. Inhibition of osteoclasts results in decreased bone resorption which is shown through decreased urinary calcium, deoxypyridinoline and cross-linked N-telopeptidases of type I collagenLabel.TargetActionsOrganismAFarnesyl pyrophosphate synthaseinhibitorHumansAHydroxylapatiteantagonistHumansUTyrosine-protein phosphatase non-receptor type inhibitorHumansUReceptor-type tyrosine-protein phosphatase SinhibitorHumansUReceptor-type tyrosine-protein phosphatase epsiloninhibitorHumansUV-type proton ATPase catalytic subunit AinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Bisphosphonates', 'Bone Density Conservation Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Musculo-Skeletal System', 'Organophosphonates', 'Organophosphorus Compounds']" +DB00961,Mepivacaine,Mepivacaineis a local anesthetic used for local or regional analgesia or anesthesia.,['Q9Y5Y9'],"Mepivicaine is an amide local anesthetic. Mepivicaine as a reasonably rapid onset and medium duration and is known by the proprietary names as Carbocaine and Polocaine. Mepivicaine is used in local infiltration and regional anesthesia. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal.",CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C,"Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans","['Local Anaesthesia therapy', 'Regional nerve block therapy', 'Lumbar epidural anesthesia therapy']","['Amides', 'Anesthetics', 'Anesthetics, Local', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Local Anesthesia', 'Local Anesthetics (Amide)', 'Methemoglobinemia Associated Agents', 'Nervous System', 'Peripheral Nervous System Agents', 'Piperidines', 'Sensory System Agents']" +DB00533,Rofecoxib,"Rofecoxibis a COX-2 inhibitor NSAID used to treat osteoarthritis, rheumatoid arthritis, acute pain, primary dysmenorrhea, and migraine attacks.","['P35354', 'P15502']","Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.",CS(=O)(=O)C1=CC=C(C=C1)C1=C(C(=O)OC1)C1=CC=CC=C1,"The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX- isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase- (COX-) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUElastinother/unknownHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Peripheral Nervous System Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Sulfur Compounds']" +DB09300,Butylscopolamine,Butylscopolamineis an antispasmodic and anticholinergic agent used for the symptomatic treatment of abdominal cramping and pain.,"['P20309', 'P08172']",Scopolamine butylbromide is a muscarinic antagonist which acts to prevent acetylcholine-stimulated contraction of smooth muscle in the gastrointestinal tract1.,CCCC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1,Scopolamine butylbromide binds to muscarinic M receptors in the gastrointestinal tract. This prevents acetycholine from binding to and activating the receptors which would result in contraction of the smooth muscle. The inhibition of contraction reduces spasms and their related pain during abdominal cramping.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans,"['Analgesia', 'Smooth muscle relaxation prior to radiological procedures therapy']","['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Alkaloids', 'Amines', 'Anticholinergic Agents', 'Antimuscarinics Antispasmodics', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Belladonna Alkaloids, Semisynthetic, Quaternary Ammonium Compounds', 'Belladonna and Derivatives, Plain', 'Cholinergic Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds', 'Scopolamine Derivatives', 'Tropanes']" +DB00450,Droperidol,Droperidolis a butyrophenone derivative and dopamine antagonist used to prevent and treat postoperative nausea and vomiting.,"['P35348', 'P14416']","Droperidol produces marked tranquilization and sedation. It allays apprehension and provides a state of mental detachment and indifference while maintaining a state of reflex alertness. Droperidol produces an antiemetic effect as evidenced by the antagonism of apomorphine in dogs. It lowers the incidence of nausea and vomiting during surgical procedures and provides antiemetic protection in the postoperative period. Droperidol potentiates other CNS depressants. It produces mild alpha-adrenergic blockade, peripheral vascular dilatation and reduction of the pressor effect of epinephrine. It can produce hypotension and decreased peripheral vascular resistance and may decrease pulmonary arterial pressure (particularly if it is abnormally high). It may reduce the incidence of epinephrine-induced arrhythmias, but it does not prevent other cardiac arrhythmias.",FC1=CC=C(C=C1)C(=O)CCCN1CCC(=CC1)N1C(=O)NC2=CC=CC=C12,"The exact mechanism of action is unknown, however, droperidol causes a CNS depression at subcortical levels of the brain, midbrain, and brainstem reticular formation. It may antagonize the actions of glutamic acid within the extrapyramidal system. It may also inhibit cathecolamine receptors and the reuptake of neurotransmiters and has strong central antidopaminergic action and weak central anticholinergic action. It can also produce ganglionic blockade and reduced affective response. The main actions seem to stem from its potent Dopamine() receptor antagonism with minor antagonistic effects on alpha- adrenergic receptors as well.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansADopamine D receptorantagonistHumans",[],"['Adjuvants, Anesthesia', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Autonomic Agents', 'Benzimidazoles', 'Butyrophenone Derivatives', 'Butyrophenones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Ketones', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Tranquilizing Agents']" +DB00455,Loratadine,Loratadineis a second generation antihistamine used to manage the symptoms of allergic rhinitis.,"['P35367', 'Q12809']","Like other 2nd generation antihistamines, loratadine is selective for peripheral H1 receptors.9Loratadine does not penetrate effectively into the central nervous system and has poor affinity for CNS H1-receptors.9These qualities result in a lack of CNS depressant effects such as drowsiness, sedation, and impaired psychomotor function.9",CCOC(=O)N1CCC(CC1)=C1C2=C(CCC3=C1N=CC=C3)C=C(Cl)C=C2,"Histamine release is a key mediator in allergic rhinitis and urticaria.As a result, loratadine exerts it's effect by targeting H histamine receptors.Loratadine binds to H histamine receptors found on the surface of epithelial cells, endothelial cells, eosinophils, neutrophils, airway cells, and vascular smooth muscle cells among others.H histamine receptors fall under the wider umbrella of G-protein coupled receptors, and exist in a state of equilibrium between the active and inactive forms.Histamine binding to the H-receptor facilitates cross linking between transmembrane domains III and V, stabilizing the active form of the receptor.On the other hand, antihistamines bind to a different site on the H receptor favouring the inactive form.Hence, loratadine can more accurately be classified as an ""inverse agonist"" as opposed to a ""histamine antagonist"", and can prevent or reduce the severity of histamine mediated symptoms.TargetActionsOrganismAHistamine H receptorantagonistHumansUPotassium voltage-gated channel subfamily H member antagonistHumans",[],"['Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Antipruritics', 'Benzocycloheptenes', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Dibenzocycloheptenes', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Loratadine and derivatives', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Piperidines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00193,Tramadol,Tramadolis a centrally-acting opioid agonist and SNRI (serotonin/norepinephrine reuptake inhibitor) used for the management of moderate to severe pain in adults.,"['P35372', 'P23975', 'P31645', 'Q99250', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'P30542', 'P08913', 'P18089', 'P18825', 'P28335', 'P41145', 'P41143', 'Q693P7', 'P20309', 'P11229', 'P25103', 'Q8NER1']","Tramadol modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin.7,6Apart from analgesia, tramadol may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids.Central Nervous SystemIn contrast tomorphine, tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no effect on heart rate, left-ventricular function or cardiac index. Orthostatic hypotension has been observed.29Tramadol produces respiratory depression by direct action on brain stem respiratory centres. The respiratory depression involves both a reduction in the responsiveness of the brain stem centres to increases in CO2 tension and to electrical stimulation.Tramadol depresses the cough reflex by a direct effect on the cough centre in the medulla. Antitussive effects may occur with doses lower than those usually required for analgesia.Tramadol causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but +are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce +similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in the setting of +oxycodone overdose.30Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range. Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures +or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, +alcohol and drug withdrawal, CNS infections), or with concomitant use of other drugs known to reduce the seizure threshold.30Tramadol can cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs (e.g., anti-depressants, migraine medications). Treatment with the serotoninergic drug should be discontinued if such events (characterized by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Tramadol should not be used in combination with MAO inhibitors or serotonin-precursors (such as L-tryptophan, oxitriptan) and should be used with caution in combination with other serotonergic drugs (triptans, certain tricyclic antidepressants, lithium, St. John’s Wort) due to the risk of serotonin syndrome.30Gastrointestinal Tract and Other Smooth MuscleTramadol causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid-induced effects may include a reduction in gastric, biliary and pancreatic secretions, spasm of the sphincter of Oddi, and transient elevations in serum amylase.30Endocrine SystemOpioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes. Some changes that can be seen include an increase in serum prolactin and decreases in plasma cortisol and testosterone. Clinical signs and symptoms may be manifest from these hormonal changes.30Hyponatremia has been reported very rarely with the use of tramadol, usually in patients with predisposing risk factors, such as elderly patients and/or patients using concomitant medications that may cause hyponatremia (e.g., antidepressants, benzodiazepines, diuretics). In some reports, hyponatremia appeared to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and resolved with discontinuation of tramadol and appropriate treatment (e.g., fluid restriction). During tramadol treatment, monitoring for signs and symptoms of hyponatremia is recommended for patients with predisposing risk factors.30CardiovascularTramadol administration may result in severe hypotension in patients whose ability to maintain adequate blood pressure is compromised by reduced blood volume, or concurrent administration of drugs such as phenothiazines and other tranquillizers, sedative/hypnotics, tricyclic antidepressants or general anesthetics. These patients should be monitored for signs of hypotension after initiating or titrating the dose of tramadol.30QTc-Interval ProlongationThe maximum placebo-adjusted mean change from baseline in the QTcF interval was 5.5 ms in the 400 mg/day treatment arm and 6.5 ms in the 600 mg/day mg treatment arm, both occurring at the 8h time point. Both treatment groups were within the 10 ms threshold for QT prolongation. Post-marketing experience with the use of tramadol containing products included rare reports of QT prolongation reported with an overdose. Particular care should be exercised when administering tramadol to patients who are suspected to be at an increased risk of experiencing torsade de pointes during treatment with a QTc-prolonging drug.30Abuse and MisuseLike all opioids, tramadol has the potential for abuse and misuse, which can lead to overdose and death. Therefore, tramadol should be prescribed and handled with caution.30Dependence/TolerancePhysical dependence and tolerance reflect the neuroadaptation of the opioid receptors to chronic exposure to an opioid and are separate and distinct from abuse and addiction. Tolerance, as well as physical dependence, may develop upon repeated administration of opioids, and are not by themselves evidence of an addictive disorder or abuse. Patients on prolonged therapy should be tapered gradually from the drug if it is no longer required for pain control. Withdrawal symptoms may occur following abrupt discontinuation of therapy or upon administration of an opioid antagonist. Some of the symptoms that may be associated with abrupt withdrawal of an opioid analgesic include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.30",COC1=CC=CC(=C1)C1(O)CCCCC1CN(C)C,"Tramadol is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related tocodeineandmorphine. Tramadol binds weakly to κ- and δ-opioid receptors and to the μ-opioid receptor with -fold less affinity than morphine.Tramadol exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic property through different mechanisms: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M) are agonists of the μ opioid receptor while (+)-tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake. These pathways are complementary and synergistic, improving tramadol's ability to modulate the perception of and response to pain.In animal models, M is up to times more potent than tramadol in producing analgesia and times more potent in μ-opioid binding.Tramadol has also been shown to affect a number of pain modulators including alpha-adrenoreceptors, neurokinin receptors, the voltage-gated sodium channel type II alpha subunit, transient receptor potential cation channel subfamily V member (TRPV - also known as the capsaicin receptor), muscarinic receptors (M and M), N-methyl-D-aspartate receptor (also known as the NMDA receptor or glutamate receptor), Adenosine A receptors, and nicotinic acetylcholine receptor.In addition to the above neuronal targets, tramadol has a number of effects on inflammatory and immune mediators involved in the pain response. This includes inhibitory effects on cytokines, prostaglandin E (PGE), nuclear factor-κB, and glial cells as well as a change in the polarization state of M macrophages.TargetActionsOrganismAMu-type opioid receptoragonistHumansASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansASodium channel protein type subunit alphainhibitorHumansANMDA receptorinhibitorHumansAAdenosine receptor AagonistHumansAAlpha- adrenergic receptorsinducerHumansU-hydroxytryptamine receptor CantagonistHumansUKappa-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansUAlpha- nicotinic cholinergic receptor subunitantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansNNeurokinin receptorinhibitorHumansNTransient receptor potential cation channel subfamily V member agonistHumans",[],"['Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Alcohols', 'Amines', 'Analgesics', 'Anticholinergic Agents', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cyclohexanes', 'Cyclohexanols', 'Cycloparaffins', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dimethylamines', 'Drugs that are Mainly Renally Excreted', 'Muscarinic Antagonists', 'Narcotics', 'Nervous System', 'NMDA Receptor Antagonists', 'Opiate Agonists', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'UGT1A1 Substrates']" +DB05381,Histamine,Histamineis an ingredient of topical drugs for the relief of joint pain or muscle aches and pains.,"['P35367', 'P25021', 'Q9Y5N1', 'Q9H3N8', 'Q05940']","Histamine stimulates gastric gland secretion, causing an increased secretion of gastric juice of high acidity. This action is probably due mainly to a direct action on parietal and chief gland cells.",NCCC1=CNC=N1,"Histamine acts directly on the blood vessels to dilate arteries and capillaries; this action is mediated by both H - and H -receptors. Capillary dilatation may produce flushing of the face, a decrease in systemic blood pressure, and gastric gland secretion, causing an increased secretion of gastric juice of high acidity. Increased capillary permeability accompanies capillary dilatation, producing an outward passage of plasma protein and fluid into the extracellular spaces, an increase in lymph flow and protein content, and the formation of edema. In addition, histamine has a direct stimulant action on smooth muscle, producing contraction if H -receptors are activated, or mostly relaxation if H -receptors are activated. Also in humans, the stimulant effect of histamine may cause contraction of the intestinal muscle. However, little effect is noticed on the uterus, bladder, or gallbladder. Histamine has some stimulant effect on duodenal, salivary, pancreatic, bronchial, and lacrimal glands. Histamine also can bind to H and H receptors which are involved in the CNS/PNS neurotransmitter release and immune system chemotaxis, respectively.TargetActionsOrganismAHistamine H receptoragonistHumansAHistamine H receptoragonistHumansAHistamine H receptoragonistHumansUHistamine H receptoragonistHumansUSynaptic vesicular amine transporterNot AvailableHumans",[],"['Adjuvants, Immunologic', 'Amines', 'Antineoplastic and Immunomodulating Agents', 'Autacoids', 'Biogenic Amines', 'Biogenic Monoamines', 'Biological Factors', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 Enzyme Inhibitors', 'Diagnostic Agents', 'Ethylamines', 'Gastric Function', 'Histamine Agents', 'Histamine Agonists', 'Imidazoles', 'Inflammation Mediators', 'Neurotransmitter Agents', 'OCT1 substrates', 'OCT2 Inhibitors', 'OCT2 Substrates', 'Other Diagnostics', 'Tests for Gastric Secretion']" +DB00886,Omapatrilat,"Omapatrilat is an investigational drug that inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). The inhibition of NEP elevates natriuretic peptide levels, increasing excretion of sodium in urine, dilating blood vessels, and reducing preload and ventricular remodeling. This drug from BMS was not approved by the FDA due to angioedema safety concerns.","['P08473', 'P12821']","Omapatrilat is used to treat hypertension. Vasopeptidase inhibitor that simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Omapatrilat lowers blood pressure by inhibiting the action of the angiotensin converting enzyme (ACE), which causes blood vessels to constrict. But unlike other drugs, omapatrilat also inhibits another enzyme known as neutral endopeptidase (NEP), which helps blood vessels relax. Omapatrilat demonstrated greater reduction in blood pressure than the ACE inhibitor lisinopril in individuals with salt-sensitive hypertension who typically do not respond well to ACE inhibitors.",[H][C@]12CCC[C@H](N1C(=O)[C@H](CCS2)NC(=O)[C@@H](S)CC1=CC=CC=C1)C(O)=O,Omapatrilat binds to both angiotensin converting enzyme and neutral endopeptidase. This results in a decrease renin-angiotensin-aldosterone production and increase natriuretic peptidase circulation.TargetActionsOrganismANeprilysinNot AvailableHumansUAngiotensin-converting enzymeNot AvailableHumans,[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Azepines', 'Cardiovascular Agents', 'Enzyme Inhibitors', 'Metalloendopeptidases, antagonists & inhibitors', 'Protease Inhibitors', 'Sulfur Compounds', 'Thiepins', 'Vasopeptidase Inhibitors']" +DB00342,Terfenadine,Terfenadineis an antihistamine for the treatment of allergy symptoms.,"['P35367', 'P20309', 'P11229', 'P08912', 'P08173', 'P08172', 'Q12809']","Terfenadine, an H1-receptor antagonist antihistamine, is similar in structure to astemizole and haloperidol, a butyrophenone antipsychotic. The active metabolite of terfenadine is fexofenadine.",CC(C)(C)C1=CC=C(C=C1)C(O)CCCN1CCC(CC1)C(O)(C1=CC=CC=C1)C1=CC=CC=C1,"Terfenadine competes with histamine for binding at H-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of terfenadine to H-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier, CNS depression is minimal.TargetActionsOrganismAHistamine H receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Anticholinergic Agents', 'Antihistamines for Systemic Use', 'Benzene Derivatives', 'Benzhydryl Compounds', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Highest Risk QTc-Prolonging Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Piperidines', 'QTc Prolonging Agents']" +DB00302,Tranexamic acid,"Tranexamic acidis an antifibrinolytic used to reduce or prevent hemorrhagic episodes, especially in the context of hyperfibrinolytic disorders.",['P00747'],"Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin.5At much higher concentrations it behaves as a noncompetitive inhibitor of plasmin similar toaminocaproic acid, a similar antifibrinolytic which is 10-fold less potent.6Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. In patients with hereditary angioedema, inhibition of the formation and activity of plasmin by tranexamic acid may prevent attacks of angioedema by decreasing plasmin-induced activation of the first complement protein (C1).3Off-target antagonism of GABA(A) receptors may be associated with the development of convulsions and hyperexcitability following tranexamic acid administration1- the risk appears higher with improper administration or administration during cardiovascular surgery.6Consider EEG monitoring of patients with a history of seizure.",NC[C@H]1CC[C@@H](CC1)C(O)=O,"Tranexamic acid competitively and reversibly inhibits the activation of plasminogen via binding at several distinct sites, including four or five low-affinity sites and one high-affinity site, the latter of which is involved in its binding to fibrin. The binding of plasminogen to fibrin induces fibrinolysis - by occupying the necessary binding sites tranexamic acid prevents this dissolution of fibrin, thereby stabilizing the clot and preventing hemorrhage.TargetActionsOrganismAPlasminogeninhibitorHumans",[],"['Acids, Carbocyclic', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Antifibrinolytic Agents', 'Blood and Blood Forming Organs', 'Coagulants', 'Cyclohexanecarboxylic Acids', 'Cyclohexanes', 'Cycloparaffins', 'Decreased Fibrinolysis', 'Fibrin Modulating Agents', 'Hematologic Agents', 'Hemostatics']" +DB00637,Astemizole,Astemizoleis a second generation antihistamine used to treat allergy symptoms.,"['P35367', 'Q12809', 'O95259', 'P10636']",Astemizole is a second generation H1-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses.,COC1=CC=C(CCN2CCC(CC2)NC2=NC3=CC=CC=C3N2CC2=CC=C(F)C=C2)C=C1,"Astemizole competes with histamine for binding at H-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier and preferentially binds at H receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H-receptors, producing adverse effects.TargetActionsOrganismAHistamine H receptorantagonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUPotassium voltage-gated channel subfamily H member Not AvailableHumansUMicrotubule-associated protein tauNot AvailableHumans",[],"['Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Benzimidazoles', 'BSEP/ABCB11 Substrates', 'BSEP/ABCB11 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Narrow Therapeutic Index Drugs', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'QTc Prolonging Agents']" +DB00881,Quinapril,"Quinaprilis an ACE inhibitor prodrug used to treat hypertension, congestive heart failure, and slow rate of progression of renal disease.",['P12821'],"Quinapril is a prodrug of an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension or adjunct in the treatment of heart failure.1,2,6Quinapril has a wide therapeutic window and a long duration of action as it is given in doses of 10-80mg once daily.6",CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC=CC=C2C[C@H]1C(O)=O,"Angiotensin II constricts coronary blood vessels and is positively inotropic, which under normal circumstances, would increase vascular resistance and oxygen consumption.This action can eventually lead to myocyte hypertrophy and vascular smooth muscle cell proliferation.Angiotensin II also stimulates production of plasminogen activator inhibitor- (PAI-), increasing the risk of thrombosis.Quinaprilat prevents the conversion of angiotensin I to angiotensin II by inhibition of angiotensin converting enzyme, and also reduces the breakdown of bradykinin.,Reduced levels of angiotensin II lead to lower levels of PAI-, reducing the risk of thrombosis, especially after a myocardial infarction.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Isoquinolines', 'OAT3/SLC22A8 Substrates', 'Protease Inhibitors', 'Tetrahydroisoquinolines']" +DB00471,Montelukast,"Montelukastis a leukotriene receptor antagonist used as part of an asthma therapy regimen, to prevent exercise induced bronchoconstriction, and to treat seasonal allergic rhinitis.","['Q9Y271', 'P09917']","Montelukast is a leukotriene receptor antagonist that demonstrates a marked affinity and selectivity to the cysteinyl leukotriene receptor type-1 in preference to many other crucial airway receptors like the prostanoid, cholinergic, or beta-adrenergic receptors.3,4,5,6,7,8,9As a consequence, the agent can elicit substantial blockage of LTD4 leukotriene-mediated bronchoconstriction with doses as low as 5 mg.3,4,5,6,7,8,9Moreover, a placebo-controlled, crossover study (n=12) demonstrated that montelukast is capable of inhibiting early and late phase bronchoconstriction caused by antigen challenge by 75% and 57% respectively.3,4,5,6,7,8,9In particular, it has been documented that montelukast can cause bronchodilation as soon as within 2 hours of oral administration.3,4,5,6,7,8,9This action can also be additive to the bronchodilation caused by the concomitant use of a beta agonist.3,4,5,6,7,8,9Nevertheless, clinical investigations performed with adults 15 years of age and older revealed that no additional clinical benefit is obtained when doses of montelukast greater than 10 mg a day are used.3,4,5,6,7,8,9Additionally, in clinical trials with adults and pediatric asthmatic patients aged 6 to 14 years, it was also determined that montelukast can reduce mean peripheral blood eosinophils by about 13% to 15% from baseline in comparison to placebo during double-blind treatment periods.3,4,5,6,7,8,9At the same time, in patients aged 15 years and older who were experiencing seasonal allergic rhinitis, the use of montelukast caused a median reduction of 13% in peripheral blood eosinophil counts when compared to placebo as well.3,4,5,6,7,8,9",OC(=O)CC1(CC1)CS[C@H](CCC1=CC=CC=C1C(O)(C)C)C1=CC=CC(\C=C\C2=NC3=C(C=CC(Cl)=C3)C=C2)=C1,"Cysteinyl leukotrienes (CysLT) like LTC, LTD, and LTE, among others, are eicosanoids released by a variety of cells like mast cells and eosinophils.,,,,,,When such CysLT bind to corresponding CysLT receptors like CysLT type- receptors located on respiratory airway smooth muscle cells, airway macrophages, and on various pro-inflammatory cells like eosinophils and some specific myeloid stem cells activities that facilitate the pathophysiology of asthma and allergic rhinitis are stimulated.,,,,,,In particular, CysLT-mediated airway bronchoconstriction, occluding mucous secretion, vascular permeability, and eosinophil recruitment are all types of effects that facilitate asthma.,,,,,,Alternatively, in allergic rhinitis, CysLTs are released by the nasal mucosa when exposed to allergens during both early and late phase reactions and participate in eliciting symptoms of allergic rhinitis like a congested nose and airway.,,,,,,Subsequently, montelukast is a leukotriene receptor antagonist that binds with high affinity and selectivity to the CysLT type receptor, which consequently assists in inhibiting any physiological actions of CysLTs like LTC, LTD, and LTE at the receptor that may facilitate asthma or allergic rhinitis.,,,,,,TargetActionsOrganismACysteinyl leukotriene receptor antagonistHumansUArachidonate -lipoxygenaseother/unknownHumans",[],"['Acids, Acyclic', 'Agents Causing Muscle Toxicity', 'Agents to Treat Airway Disease', 'Anions', 'Anti-Asthmatic Agents', 'Cycloparaffins', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Electrolytes', 'Fatty Acids', 'Fatty Acids, Volatile', 'Heterocyclic Compounds, Fused-Ring', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydrogen Sulfide', 'Ions', 'Leukotriene Antagonists', 'Leukotriene Modifiers', 'Lipids', 'OATP2B1/SLCO2B1 substrates', 'Respiratory System Agents', 'Sulfur Compounds']" +DB00513,Aminocaproic acid,Aminocaproic acidis an antifibrinolytic agent used to induce clotting postoperatively.,"['P00747', 'P00750', 'P08519']","Aminocaproic acid works as an antifibrinolytic. It is a derivative of the amino acid lysine. The fibrinolysis-inhibitory effects of aminocaproic acid appear to be exerted principally via inhibition of plasminogen activators and to a lesser degree through antiplasmin activity. Aminocaproic acid may be a possible prophylactic for vascular disease, as it may prevent formation of lipoprotein (a), a risk factor for vascular disease.",NCCCCCC(O)=O,"Aminocaproic acid binds reversibly to the kringle domain of plasminogen and blocks the binding of plasminogen to fibrin and its activation to plasmin. With NO activation of plasmin, there is a reduction in fibrinolysis. This consequently will reduce the amount of bleeding post surgery. Elevated plasma levels of lipoprotein(a) have been shown to increase the risk of vascular disease. Lipoprotein a)a has two components, apolipoprotein B-, linked to apolipoprotein (a). Aminocaproic acid may change the conformation of apoliprotein (a), changing its binding properties and potentially preventing the formation of lipoprotein (a).TargetActionsOrganismAPlasminogeninhibitorHumansATissue-type plasminogen activatorantagonistHumansUApolipoprotein(a)otherHumans",[],"['Acids, Acyclic', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Aminocaproates', 'Antifibrinolytic Agents', 'Blood and Blood Forming Organs', 'Caproates', 'Coagulants', 'Decreased Fibrinolysis', 'Fibrin Modulating Agents', 'Hematologic Agents', 'Hemostatics']" +DB06148,Mianserin,Mianserinis a tetracyclic antidepressant with therapeutic activity similar to amitriptyline used to treat depression and anxiety.,"['P08913', 'P28223', 'P28335', 'P35367', 'P23975', 'P31645', 'Q9H3N8', 'P08908', 'P18825', 'P41595', 'P30939', 'P18089', 'P35462', 'P41145', 'Q01959', 'P34969', 'P14416', 'P50406', 'P35348', 'P35368', 'P25100', 'P21728', 'P21918']","Mianserin is a tetracyclic antidepressant that has antihistaminic and hypnosedative, but almost no anticholinergic, effect. It is a weak inhibitor of norepinephrine reuptake and strongly stimulates the release of norepinephrine. Interactions with serotonin receptors in the central nervous system have also been found. Its effect is usually noticeable after one to three weeks. Mianserin may cause drowsiness and hematological problems.",CN1CCN2C(C1)C1=CC=CC=C1CC1=CC=CC=C21,"Mianserin's mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H, and some types of serotonin receptors.TargetActionsOrganismUAlpha-A adrenergic receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUHistamine H receptorantagonistHumansUSodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent serotonin transporterinhibitorHumansUHistamine H receptorbinderHumansU-hydroxytryptamine receptor AblockerHumansUAlpha-C adrenergic receptorantagonistHumansU-hydroxytryptamine receptor BbinderHumansU-hydroxytryptamine receptor FbinderHumansUAlpha-B adrenergic receptorantagonistHumansUDopamine D receptorbinderHumansUKappa-type opioid receptoragonistHumansUSodium-dependent dopamine transporterbinderHumansU-hydroxytryptamine receptor antagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor binderHumansUAlpha- adrenergic receptorsantagonistHumansUD() dopamine receptorbinderHumans",[],"['Adrenergic Agents', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antidepressive Agents, Second-Generation', 'Antidepressive Agents, Tetracyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dibenzazepines', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists']" +DB00903,Etacrynic acid,"Etacrynic acidis a diuretic used to treat ascites and edema in congestive heart failure, liver cirrhosis, and renal disease.","['Q13621', 'P05023', 'Q9UJU2', 'P09211']","Ethacrynic acid is a monosulfonamyl loop or high ceiling diuretic. Ethacrynic acid acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Ethacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis.",CCC(=C)C(=O)C1=C(Cl)C(Cl)=C(OCC(O)=O)C=C1,"Ethacrynic acid inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. Diuretics also lower blood pressure initially by reducing plasma and extracellular fluid volume; cardiac output also decreases, explaining its antihypertensive action. Eventually, cardiac output returns to normal with an accompanying decrease in peripheral resistance. Its mode of action does not involve carbonic anhydrase inhibition.TargetActionsOrganismASolute carrier family member inhibitorHumansASodium/potassium-transporting ATPase subunit alpha-inhibitorHumansULymphoid enhancer-binding factor Not AvailableHumansUGlutathione S-transferase PinhibitorHumans",[],"['Acetates', 'Acids, Acyclic', 'Agents that produce neuromuscular block (indirect)', 'Aryloxyacetic Acid Derivatives', 'Diuretics', 'Enzyme Inhibitors', 'Glycolates', 'High-Ceiling Diuretics', 'Hydroxy Acids', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis at Loop of Henle', 'Natriuretic Agents', 'Nephrotoxic agents', 'Non Potassium Sparing Diuretics', 'OAT1/SLC22A6 inhibitors', 'Ototoxic agents', 'Phenoxyacetates', 'Sodium Potassium Chloride Symporter Inhibitors']" +DB01365,Mephentermine,Mephentermineis a sympathomimetic agent used in the treatment of hypotension.,"['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945']","Mephentermine is a sympathomimetic agent with mainly indirect effects on adrenergic receptors. It is used to maintain blood pressure in hypotensive states, for example, following spinal anesthesia. Although the central stimulant effects of mephentermine are much less than those of amphetamine, its use may lead to amphetamine-type dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1248)",CNC(C)(C)CC1=CC=CC=C1,"Mephentermine is an alpha adrenergic receptor agonist, but also acts indirectly by releasing endogenous norepinephrine. Cardiac output and systolic and diastolic pressures are usually increased. A change in heart rate is variable, depending on the degree of vagal tone. Sometimes the net vascular effect may be vasodilation. Large doses may depress the myocardium or produce central nervous system (CNS) effects.TargetActionsOrganismAAlpha adrenergic receptoragonistHumansUBeta adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Amphetamines', 'Autonomic Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Ethylamines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB00673,Aprepitant,Aprepitantis a substance P/neurokinin 1 receptor antagonist used to treat nausea and vomiting caused by chemotherapy and surgery.,['P25103'],"Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).",C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F,"Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the -HT-receptor antagonist ondansetron and the corticosteroid +ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis.TargetActionsOrganismANeurokinin receptorantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antiemetics', 'Antiemetics and Antinauseants', 'Aprepitant and Prodrugs', 'Autonomic Agents', 'Central Nervous System Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Gastrointestinal Agents', 'Morpholines', 'Neurokinin 1 Antagonists', 'Neurokinin-1 Receptor Antagonists', 'Neurotransmitter Agents', 'Oxazines', 'Peripheral Nervous System Agents', 'Substance P/Neurokinin-1 Receptor Antagonist']" +DB05630,Sodium stibogluconate,"Sodium stibogluconate is a medicine used to treat leishmaniasis and is only available for administration by injection. It belongs to the class of medicines known as the pentavalent antimonials. Sodium stibogluconate is sold in the UK as Pentostam (manufactured by GlaxoSmithKline). Widespread resistance has limited the utility of sodium stibogluconate, and in many parts of the world, amphotericin or miltefosine are used instead. It is also being investigated as an anti-tumor agent.",['P11387'],"The mode of action of sodium stibogluconate is not clearly understood. In vitro exposure of amastigotes to 500 mg pentavalent antimony/ml results in a greater than 50% decrease in parasite DNA, RNA protein and purine nucleoside triphosphate levels. It has been postulated that the reduction in ATP (adenosine triphosphate) and GTP (guanosine triphosphate) synthesis contributes to decreased macromolecular synthesis.",O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[H][C@@]1(O[Sb]2(O)(O[Sb]34([O-])O[C@@H](C([O-])=O)[C@@]([H])(O3)[C@]([H])(O4)[C@H](O)CO)O[C@@H](C([O-])=O)[C@@]1([H])O2)[C@H](O)CO,Sodium stibogluconate directly inhibits DNA topoisomerase I leading to inhibition of both DNA replication and transcription.TargetActionsOrganismADNA topoisomerase inhibitorHumans,[],"['Acids, Acyclic', 'Agents Against Leishmaniasis and Trypanosomiasis', 'Anti-Infective Agents', 'Antimony Compounds', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiplatyhelmintic Agents', 'Antiprotozoals', 'Carbohydrates', 'Gluconates', 'Hydroxy Acids', 'Schistosomicides', 'Sugar Acids']" +DB09401,Isosorbide,Isosorbideis a vasodilator used for the prevention and treatment of angina pectoris due to coronary artery disease. It was previously used to reduce intraocular pressure.,"['Q02108', 'P33402', 'Q02153', 'O75343']","Isosorbide reduces intraocular pressure through its effects on ocular blood vessels.8,12While in the blood, isosorbide promotes redistribution of water toward the circulation, promoting the excretion of urine.12",[H][C@]1(O)CO[C@]2([H])[C@]([H])(O)CO[C@]12[H],"Isosorbide causes vascular relaxation, reducing systolic ophthalmic artery pressure (SOAP), systolic ocular perfusion pressure (SOPP).TargetActionsOrganismAGuanylate cyclaseactivatorHumans",[],"['Alcohols', 'Antianginal Agents', 'Carbohydrates', 'Cardiovascular Agents', 'Diuretics', 'Diuretics, Osmotic', 'Natriuretic Agents', 'Noxae', 'Organic Nitrates', 'Terpenes', 'Vasodilating Agents']" +DB00889,Granisetron,Granisetronis a 5HT3 antagonist used to treat nausea and vomiting in cancer therapy and postoperatively.,['P46098'],"Granisetron is a selective inhibitor of type 3 serotonergic (5-HT3) receptors. Granisetron has little or no affinity for other serotonin receptors, including 5-HT 1 , 5-HT 1A , 5-HT 1B/C , or 5-HT 2 ; for alpha 1 -, alpha 2 -, or beta-adrenoreceptors; for dopamine D 2 receptors; for histamine H 1 receptors; for benzodiazepine receptors; for picrotoxin receptors; or for opioid receptors. In most human studies, granisetron has had little effect on blood pressure, heart rate, or electrocardiogram (ECG). The drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT3receptors. The serontonin 5-HT3receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.",CN1N=C(C(=O)N[C@@H]2C[C@@H]3CCC[C@H](C2)N3C)C2=C1C=CC=C2,"Granisetron is a potent, selective antagonist of -HTreceptors. The antiemetic activity of the drug is brought about through the inhibition of -HT receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of -HT receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'Antiemetic Serotonin 5-HT3 Receptor Antagonists', 'Antiemetics', 'Antiemetics and Antinauseants', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Indazoles', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Pyrazoles', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 3 Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB01068,Clonazepam,"Clonazepamis a long-acting benzodiazepine with intermediate onset commonly used to treat panic disorders, severe anxiety, and seizures.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928', 'O75469']","The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects6,18,22,23. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and wavesLabel6,18,22,23. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizuresLabel22.Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes18. Clonazepam has beneficial effects in generalized and focal epilepsies18.",[O-][N+](=O)C1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2Cl)C=C1,"Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body,,. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors,,,. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons,,,.Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors,,,,,. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors,,,,,. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells,,,,,. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action,,,,,.In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted - resulting in seizure activity. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures. Concurrently, it is also believed that clonazepam's actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits - therefore assisting in the management of anxiety or panic.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumansUNuclear receptor subfamily group I member partial agonistHumans",[],"['Anticonvulsants', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System']" +DB00232,Methyclothiazide,"Methyclothiazideis a diuretic drug used to treat hypertension and edema caused by heart failure, renal conditions, treatment with corticosteroids, and estrogen therapy.","['Q13621', 'P00915', 'P00918', 'P22748']","Methyclothiazide, a diuretic-antihypertensive agent, is a member of the benzothiadiazine (thiazide) class of drugs. Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic/natriuretic effects. Like other benzothiadiazines, methyclothiazide also has antihypertensive properties, and may be used for this purpose either alone or to enhance the antihypertensive action of other drugs.",CN1C(CCl)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O,"Methyclothiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, methyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like methyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of methyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.TargetActionsOrganismASolute carrier family member inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Benzothiadiazines', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Photosensitizing Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB00628,Clorazepic acid,"Clorazepic acidis a benzodiazepine used to treat anxiety, partial seizures, and alcohol withdrawal.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Pharmacologically, clorazepate has the characteristics of benzodiazepines. Studies in healthy men have shown that clorazepate has depressant effects on the central nervous system. Since orally administered clorazepate dipotassium is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug.8The use of benzodiazepines, including clorazepate, exposes users to abuse, misuse, and addiction risks, which can lead to overdose and death. Patients treated with clorazepate may also develop suicidal behavior and ideation, and the use of clorazepate may cause interference with psychomotor performance. The concomitant use of clorazepate with opioids may result in profound sedation, respiratory depression, coma, and death.8",OC(=O)C1N=C(C2=CC=CC=C2)C2=C(NC1=O)C=CC(Cl)=C2,"Clorazepate is a benzodiazepine with depressant effects on the central nervous system.Benzodiazepines are able to enhance the binding of gamma-aminobutyric acid (GABA) to the GABA type A (GABA-A) receptor by binding to a region in the extracellular domain found at the interface between the alpha (α) and gamma (γ) subunits of the GABA-A receptor. The interaction of GABA and the GABA-A receptor promotes channel opening, leading to an increased chloride influx. Consequently, the use of benzodiazepines, such as clorazepate, leads to neuronal hyperpolarization.,TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Anticonvulsants', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB01105,Sibutramine,"Sibutramineis a norepinephrine, serotonin and dopamine reuptake inhibitor indicated to assist with weight loss in obesity.","['Q01959', 'P31645', 'P23975']","Sibutramine is an orally administered agent for the treatment of obesity. Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound, sibutramine, is a potent inhibitor of serotonin and norepinephrine reuptakein vivo, but notin vitro. However, metabolites M1 and M2 inhibit the reuptake of these neurotransmitters bothin vitroandin vivo. In human brain tissue, M1 and M2 also inhibit dopamine reuptakein vitro, but with ~3-fold lower potency than for the reuptake inhibition of serotonin or norepinephrine. Sibutramine, M1 and M2 exhibit no evidence of anticholinergic or antihistaminergic actions. In addition, receptor binding profiles show that sibutramine, M1 and M2 have low affinity for serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), norepinephrine (b, b1, b3, a1 and a2), dopamine (D1 and D2), benzodiazepine, and glutamate (NMDA) receptors. These compounds also lack monoamine oxidase inhibitory activityin vitroandin vivo.",CC(C)CC(N(C)C)C1(CCC1)C1=CC=C(Cl)C=C1,"Sibutramine produces its therapeutic effects by inhibition of norepinephrine (NE), serotonin (-hydroxytryptamine, -HT), and to a lesser extent, dopamine reuptake at the neuronal synapse. By inhibiting the reuptake of these neurotransmitters, sibutramine promotes a sense of satiety and decrease in appetite, thereby reducing food intake. Data from animal studies also suggest that sibutramine may also increase energy expenditure through thermogenic effects in both the basal and fed states, but this has not been confirmed in humans. Sibutramine and its major pharmacologically active metabolites (M and M) do not act via release of monoamines.TargetActionsOrganismASodium-dependent dopamine transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Anti-Obesity Agents', 'Antidepressive Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Appetite Depressants', 'Appetite Suppression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cycloparaffins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Uptake Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Norepinephrine Uptake Inhibitors', 'Norepinephrine, Serotonin, and Dopamine Reuptake Inhibitor Anorectic', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin and Noradrenaline Reuptake Inhibitors', 'Serotonin Modulators', 'Stimulants']" +DB00116,Tetrahydrofolic acid,"Tetrahydrofolic acid is a folic acid derivative that is produced from dihydrofolic acid after conversion by dihydrofolate reductase. It is converted into 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase. It is a soluble coenzyme in many reactions, especially in the metabolism of amino acids and nucleic acids.","['P11586', 'P13995', 'P48728', 'O75891', 'Q99707', 'O95954', 'P31939', 'P34896', 'P34897', 'P42898', 'Q53ET4', 'Q96DP5']","Tetrahydrofolate is the main active metabolite of dietary folate. It is vital as a coenzyme in reactions involving transfers of single carbon groups. Tetrahydrofolate has a role in nucleic and amino acid synthesis. As nucleic and amino acid synthesis is affected by a deficiency of tetrahydrofolate, actively dividing and growing cells tend to be the first affected. Tetrahydrofolate is used to treat topical sprue and megaloblastic and macrocytic anemias, hematologic complications resulting from a deficiency in folic acid.",NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2)N1,"Tetrahydrofolate is transported across cells by receptor-mediated endocytosis where it is needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate.TargetActionsOrganismUC--tetrahydrofolate synthase, cytoplasmiccofactorHumansUBifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialcofactorHumansUAminomethyltransferase, mitochondrialcofactorHumansUCytosolic -formyltetrahydrofolate dehydrogenasecofactorHumansUMethionine synthasecofactorHumansUFormimidoyltransferase-cyclodeaminasecofactorHumansUBifunctional purine biosynthesis protein PURHcofactorHumansUSerine hydroxymethyltransferase, cytosoliccofactorHumansUSerine hydroxymethyltransferase, mitochondrialcofactorHumansUMethylenetetrahydrofolate reductasecofactorHumansUSerine hydroxymethyltransferasecofactorHumansUMethionyl-tRNA formyltransferase, mitochondrialcofactorHumans",[],"['Coenzymes', 'Dietary Supplements', 'Enzymes and Coenzymes', 'Folic Acid and Derivatives', 'Heterocyclic Compounds, Fused-Ring', 'Pteridines', 'Pterins', 'Supplements', 'Vitamin B Complex', 'Vitamins']" +DB00498,Phenindione,"An indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234)",['Q9BQB6'],"Phenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects.",O=C1C(C(=O)C2=CC=CC=C12)C1=CC=CC=C1,"Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.TargetActionsOrganismAVitamin K epoxide reductase complex subunit inhibitorHumans",[],"['Anticoagulants', 'Blood and Blood Forming Organs', 'Hematologic Agents', 'Indans', 'Indenes', 'Narrow Therapeutic Index Drugs', 'Vitamin K Antagonists']" +DB00434,Cyproheptadine,"Cyproheptadineis a combined serotonin and histamine antagonist used in the treatment of allergic symptoms, for appetite stimulation, and off-label in the treatment of serotonin syndrome.","['P35367', 'P28223', 'P28335', 'P25021', 'P41595', 'P11229', 'P08172', 'P20309', 'P34969']","Cyproheptadine has been observed to antagonize several pharmacodynamic effects of serotonin in laboratory animals, including bronchoconstriction and vasodepression, and has demonstrated similar efficacy in antagonizing histamine-mediated effects.9The reason for its efficacy in preventing anaphylactic shock has not been elucidated, but appears to be related to its anti-serotonergic effects.9",CN1CCC(CC1)=C1C2=CC=CC=C2C=CC2=CC=CC=C12,Cyproheptadine appears to exert its antihistamine and antiserotonin effects by competing with free histamine and serotonin for binding at their respective receptors.Antagonism of serotonin on the appetite center of the hypothalamus may account for cyproheptadine's ability to stimulate the appetite.TargetActionsOrganismAHistamine H receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor CantagonistHumansUHistamine H receptorantagonistHumansU-hydroxytryptamine receptor BantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansU-hydroxytryptamine receptor antagonistHumans,['Appetite stimulation'],"['Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Anti-Allergic Agents', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antihistamines for Systemic Use', 'Antipruritics', 'Benzocycloheptenes', 'Central Nervous System Depressants', 'Dermatologicals', 'Dibenzocycloheptenes', 'Drugs causing inadvertant photosensitivity', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Miscellaneous Derivatives', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'Photosensitizing Agents', 'Piperidines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'UGT1A3 substrates', 'UGT1A4 substrates']" +DB00581,Lactulose,Lactuloseis a disaccharide derivative of lactose used to treat constipation and portal systemic encephalopathy.,['P06864'],"Lactulose formulations are most commonly administered via the oral route or the rectal route.4Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut.Label,3,4In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.Label,3,4",OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O,"Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose.Label,,Saccharolytic bacteria present in the large intestine subsequently break the substance down into organic acids like lactic acid and small amounts of formic and acetic acids.Label,,Such resultant volatile fatty acid metabolites, in combination with hydrogen and methane that is also generated consequently enhance intraluminal gas formation, peristaltic gut motility, and elicit an osmotic effect that facilitates an increase in the water content of stool as well as associated stool softening.Label,,All of these actions ultimately assist in facilitating and increasing the frequency of bowel movements in patients experiencing constipation, although it may take to hours after using the medication for this laxative effect to become evident.Label,,At the same time, the formation of such acids via the metabolism of lactulose by colonic bacteria also acidifies the contents of the colon, thereby contributing to the treatment of portal-systemic encephalopathy (PSE).Label,,As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.Label,,. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood.Label,,These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia.Label,,And finally, it is also believed that an acidic colonic environment results in the elimination of urease-producing bacteria that contribute to the formation of ammonia while surviving colonic bacteria use up any trapped ammonia in the colon as a source of nitrogen for protein synthesis.TargetActionsOrganismUEvolved beta-galactosidase subunit alphaotherEscherichia coli (strain K)",[],"['Acidifying Activity', 'Alimentary Tract and Metabolism', 'Ammonia Detoxicants', 'Carbohydrates', 'Disaccharides', 'Drugs for Constipation', 'Gastrointestinal Agents', 'Laxatives', 'Osmotic Activity', 'Osmotic Laxatives', 'Stimulation Large Intestine Fluid/Electrolyte Secretion']" +DB00173,Adenine,Adenineis a purine base which forms a component of DNA among other functions and is present in many multivitamins.,"['P07741', 'Q13126', 'Q05603', 'O00763', 'P24666', 'P0AF12', 'Q9BY49', 'P17802', 'Q8RLY5', 'P78362', 'Q5SL87']","Adenine (sometimes known as vitamin B4) combines with the sugar ribose to form adenosine, which in turn can be bonded with from one to three phosphoric acid units, yielding AMP, ADP and ATP . These adenine derivatives perform important functions in cellular metabolism. Adenine is one of four nitrogenous bases utilized in the synthesis of nucleic acids. A modified form of adenosine monophosphate (cyclic AMP) is an imporant secondary messenger in the propagation of many hormonal stimuli. Adenine is an integral part of the structure of many coenzymes. Adenosine (adenine with a ribose group) causes transient heart block in the AV node of the heart. In individuals suspected of suffering from a supraventricular tachycardia (SVT), adenosine is used to help identify the rhythm. Certain SVTs can be successfully terminated with adenosine.",NC1=C2NC=NC2=NC=N1,"Adenine forms adenosine, a nucleoside, when attached to ribose, and deoxyadenosine when attached to deoxyribose, and it forms adenosine triphosphate (ATP), which drives many cellular metabolic processes by transferring chemical energy between reactions.TargetActionsOrganismUAdenine phosphoribosyltransferaseNot AvailableHumansUDNANot AvailableHumansUS-methyl-'-thioadenosine phosphorylaseNot AvailableHumansUNicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferaseNot AvailableSalmonella typhimurium (strain LT / SGSC / ATCC )UAcetyl-CoA carboxylase Not AvailableHumansULow molecular weight phosphotyrosine protein phosphataseNot AvailableHumansU'-methylthioadenosine/S-adenosylhomocysteine nucleosidaseNot AvailableEscherichia coli (strain K)UPeroxisomal trans--enoyl-CoA reductaseNot AvailableHumansUA/G-specific adenine glycosylaseNot AvailableEscherichia coli (strain K)UNucleoside deoxyribosyltransferase-INot AvailableLactobacillus helveticusUSRSF protein kinase Not AvailableHumansUHolliday junction ATP-dependent DNA helicase RuvBNot AvailableThermus thermophilus (strain HB / ATCC / DSM )",[],"['Dietary Supplements', 'Heterocyclic Compounds, Fused-Ring', 'Purines', 'Supplements', 'UGT1A1 Inhibitors']" +DB01198,Zopiclone,Zopicloneis a nonbenzodiazepine hypnotic used for the short-term management of insomnia.,"['P14867', 'P47869', 'P34903', 'P31644', 'P30536']","Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.",CN1CCN(CC1)C(=O)OC1N(C(=O)C2=NC=CN=C12)C1=NC=C(Cl)C=C1,"Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α, α, α and α GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUTranslocator proteinagonistHumans",[],"['Aza Compounds', 'Benzodiazepine hypnotics and sedatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Hypnotics (Nonbenzodiazepine)', 'Hypnotics and Sedatives', 'Methemoglobinemia Associated Agents', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Nervous System', 'Photosensitizing Agents', 'Psycholeptics', 'Sleep Initiation and Maintenance Disorders', 'Zopiclone and prodrugs']" +DB04867,Lintitript,"Lintitript is a new, highly specific and potent CCK-A receptor antagonist.",['P32238'],"Lintitript SR 27897 is a selective cholecystokinin type A (CCK-A) receptor antagonist. In February 2000, Sanofi announced that it was halting development of the drug for appetite disorders, and in September 2002, Sanofi announced that it had stopped investigation all together.",OC(=O)CN1C(=CC2=CC=CC=C12)C(=O)NC1=NC(=CS1)C1=CC=CC=C1Cl,"Cholecystokinin (CCK) modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. Lintitript antagonizes the effect of cholecystokinin by binding to the cholecystokinin type A (CCK-A) receptor. This action presumably alters feeding habits, however the exact mechanism of action is not known.TargetActionsOrganismUCholecystokinin receptor type ANot AvailableHumans",[],"['Heterocyclic Compounds, Fused-Ring', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Indoles', 'Sulfur Compounds']" +DB00567,Cephalexin,Cephalexinis a first generation cephalosporin used to treat certain susceptible bacterial infections.,"['Q75Y35', 'Q8DNB6', 'Q7CRA4', 'P0A3M6', 'Q8DR59']","Cephalexin (also called Cefalexin) is a first generation cephalosporin antibiotic.7,8It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations.LabelIt is effective against most gram-positive bacteria through its inihibition of the cross linking reaction between N-acetyl muramicacid and N-acetylglucosamine in the cell wall, leading to cell lysis.9",[H][C@]12SCC(C)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(O)=O,"Cephalexin is a first generation cephalosporin antibiotic.,Cephalosporins contain a beta lactam and dihydrothiazide.Unlike penicillins, cephalosprins are more resistant to the action of beta lactamase.Cephalexin inhibits bacterial cell wall synthesis, leading breakdown and eventualy cell death.LabelTargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Aza Compounds', 'Azabicyclo Compounds', 'beta-Lactams', 'Cephalosporins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'First-Generation Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'MATE 1 Substrates', 'MATE substrates', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Sulfur Compounds', 'Thiazines']" +DB00211,Midodrine,Midodrineis an alpha-adrenergic agonist used to treat orthostatic hypotension.,"['P35348', 'P35368', 'P25100']","Midodrine is a prodrug, i.e., the therapeutic effect of orally administered midodrine is due to the major metabolite desglymidodrine formed by deglycination of midodrine. Administration of midodrine results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies. Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10-mg dose of midodrine, with some effect persisting for 2 to 3 hours. Midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.",COC1=CC(C(O)CNC(=O)CN)=C(OC)C=C1,"Midodrine undergoes metabolism to form its pharmacologically active metabolite, desglymidodrine. Desglymidodrine acts as an agonist at the alpha-adrenergic receptors expressed in the arteriolar and venous vasculature. Activation of alpha-adrenergic receptor signaling pathways lead to an increase in the vascular tone and elevation of blood pressure. Desglymidodrine is reported to have negligible effect on the cardiac beta-adrenergic receptors.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansUAlpha-D adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Autonomic Agents', 'Bradycardia-Causing Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Ethanolamines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB01077,Etidronic acid,Etidronic acidis a bisphosphonate drug that prevents osteoclastic bone resorption; used for the prevention and treatment of osteoporosis.,"['Q13332', 'P38606', 'P12235', 'P05141', 'P12236']","Etidronic acid is a first generation bisphosphonate that inhibits the action of osteoclasts, preventing bone resporption.7It has a wide therapeutic index as overdoses are not associated with severe toxicity and a long duration of action as it slowly releases from the bone.7Patients should be counselled regarding the risk of upper gastrointestinal adverse reactions.7",CC(O)(P(O)(O)=O)P(O)(O)=O,"Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis.Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.Osteoclasts mediate resorption of bone.When osteoclasts bind to bone they form podosomes, ring structures of F-actin.Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.First generation bisphosphonates closely mimic the structure of pyrophosphate, which can be incorporated into ATP anologues that cannot be hydrolyzed, disrupting all ATP mediated actions of osteoclasts.TargetActionsOrganismAHydroxylapatiteantagonistHumansUReceptor-type tyrosine-protein phosphatase SinhibitorHumansUV-type proton ATPase catalytic subunit AinhibitorHumansUADP/ATP translocase inhibitorHumansUADP/ATP translocase inhibitorHumansUADP/ATP translocase inhibitorHumans",[],"['Bisphosphonates', 'Bone Density Conservation Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Musculo-Skeletal System', 'Organophosphonates', 'Organophosphorus Compounds']" +DB01211,Clarithromycin,"Clarithromycinis a macrolide antibiotic used for the treatment of a wide variety of bacterial infections such as acute otitis, pharyngitis, tonsillitis, respiratory tract infections, uncomplicated skin infections, and helicobacter pylori infection.","['P0A7J6', 'Q12809', 'Q9Y6L6', 'Q9NPD5']","Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) and gram-negative aerobic bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, some mycobacteria, and some other organisms includingMycoplasma, Ureaplasma, Chlamydia, Toxoplasma, andBorrelia. Other aerobic bacteria that clarithromycin has activity against includeC. pneumoniae and M. pneumoniae. Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration.",[H][C@@]1(C[C@@](C)(OC)[C@@H](O)[C@H](C)O1)O[C@H]1[C@H](C)[C@@H](O[C@]2([H])O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@@](C)(C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC(=O)[C@@H]1C)OC,"Clarithromycin is first metabolized to -OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the S ribosomal RNA of the S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYPA isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.TargetActionsOrganismAS ribosomal protein LinhibitorShigella flexneriUPotassium voltage-gated channel subfamily H member Not AvailableHumansUSolute carrier organic anion transporter family member BNot AvailableHumansUSolute carrier organic anion transporter family member BNot AvailableHumans",[],"['Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Enzyme Inhibitors', 'Erythromycin and similars', 'Lactones', 'Macrolide Antimicrobial', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'Moderate Risk QTc-Prolonging Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Other Macrolides', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Polyketides', 'Protein Synthesis Inhibitors', 'QTc Prolonging Agents']" +DB01006,Letrozole,Letrozoleis an aromatase inhibitor used to treat breast cancer in postmenopausal women.,['P11511'],"Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue.Letrozole is a third generation type II aromatase inhibitor used to treat estrogen dependant breast cancers.9It has a long duration of action as it has a half life of over 42 hours in breast cancer patients.2,4,9Patients should be counselled regarding the risk of interstitial lung disease, pneumonitis, QT prolongation, elevated transaminase levels, neutropenia, and embryo-fetal toxicity.9",N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N,"Letrozole is a non-steroidal type II aromatase inhibitor.It blocks the active site, and therefore the electron transfer chain of CYPA.This competitive inhibition prevents the conversion of androgens to estrogen.This action leads to a reduction in uterine weight and elevated leuteinizing hormone.In postmenopausal women, the action of aromatase is responsible for the majority of estrogen production.With reduced availability of estrogen, estrogen-dependant tumors regress.Third generation aromatase inhibitors do not significantly affect cortisol, aldosterone, and thyroxine levels.TargetActionsOrganismACytochrome P AantagonistHumans",[],"['Agents Causing Muscle Toxicity', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Aromatase Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strong)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Enzyme Inhibitors', 'Estrogen Antagonists', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Nitriles', 'P-glycoprotein substrates', 'Steroid Synthesis Inhibitors', 'Triazoles', 'UGT2B7 substrates']" +DB01956,Taurine,Taurineis an ingredient found in mixture products indicated for nutritional support.,"['Q13224', 'P23416', 'O75311', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'Q9UBS5', 'P23415', 'P37610', 'P54965']","The diet supplements containing taurine are formulated as a well-tolerated nitrogen source for nutritional support. Administration of diet supplements regulates the level of plasma amino acid concentration, nitrogen balance, weight and serum protein concentration to reach normal values, thus improving the nutritional status.Label",NCCS(O)(=O)=O,"The diet supplements containing taurine function by replacing the missing nutriments in the body. Taurine, as a single agent, presents different functions like substrate for formation of bile salts, cell volume regulation, modulation of intracellular calcium, cytoprotection of central nervous system, etc.TargetActionsOrganismAGlutamate receptor ionotropic, NMDA BinhibitorHumansAGlycine receptor subunit alpha-agonistHumansAGlycine receptor subunit alpha-agonistHumansAGABA(A) ReceptoragonistHumansAGamma-aminobutyric acid type B receptor subunit agonistHumansUGlycine receptor subunit alpha-agonistHumansUAlpha-ketoglutarate-dependent taurine dioxygenaseNot AvailableEscherichia coli (strain K)UCholoylglycine hydrolaseNot AvailableClostridium perfringens (strain / Type A)",['Total parenteral nutrition therapy'],"['Alkanes', 'Alkanesulfonic Acids', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Hydrocarbons, Acyclic', 'Sulfonic Acids', 'Sulfur Acids', 'Sulfur Compounds']" +DB01182,Propafenone,Propafenoneis a Class 1C antiarrhythmic agent used in the management of paroxysmal atrial fibrillation/flutter and ventricular arrhythmias.,"['Q14524', 'Q12809', 'P08588', 'P07550']","Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It acts by inhibiting sodium channels to restrict the entry of sodium into cardiac cells resulting in reduced excitation. Propafenone has local anesthetic activity approximately equal to procaine.",CCCNCC(O)COC1=C(C=CC=C1)C(=O)CCC1=CC=CC=C1,"The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase ) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansAPotassium voltage-gated channel subfamily H member inhibitorHumansUBeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ic', 'Bradycardia-Causing Agents', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ketones', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'P-glycoprotein inhibitors', 'Propiophenones', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB00229,Cefotiam,Cefotiamis a cephalosporin antibiotic used to treat a variety of bacterial infections.,['Q8XJ01'],Cefotiam is a third generation beta-lactam cephalosporin antibiotic that works by inhibiting bacterial cell wall biosynthesis. It is a broad spectrum antibiotic that is effective against Gram positive and Gram negative bacteria.,[H][C@]12SCC(CSC3=NN=NN3CCN(C)C)=C(N1C(=O)[C@H]2NC(=O)CC1=CSC(N)=N1)C(O)=O,The bactericidal activity of cefotiam results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).TargetActionsOrganismAPenicillin-binding protein AinducerClostridium perfringens (strain / Type A),[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB00325,Nitroprusside,"Nitroprussideis a direct acting vasodilator used to treat hypertension, to induce controlled hypotension to reduce postoperative bleeding, and to manage acute heart failure.",['P16066'],"Nitroprusside a powerful vasodilator relaxes the vascular smooth muscle and produce consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries.",O=N[Fe--](C#N)(C#N)(C#N)(C#N)C#N,"One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN- ions; methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin; thiosulfate reacts with cyanide to produce thiocyanate; thiocyanate is eliminated in the urine; cyanide not otherwise removed binds to cytochromes. Cyanide ion is normally found in serum; it is derived from dietary substrates and from tobacco smoke. Cyanide binds avidly (but reversibly) to ferric ion (Fe+++), most body stores of which are found in erythrocyte methemoglobin (metHgb) and in mitochondrial cytochromes. When CN is infused or generated within the bloodstream, essentially all of it is bound to methemoglobin until intraerythrocytic methemoglobin has been saturated.Sodium nitroprusside is further broken down in the circulation to release nitric oxide (NO), which activates guanylate cyclase in the vascular smooth muscle. This leads to increased production of intracellular cGMP, which stimulates calcium ion movement from the cytoplasm to the endoplasmic reticulum, reducing the level of available calcium ions that can bind to calmodulin. This ultimately results in vascular smooth muscle relaxation and vessel dilation.TargetActionsOrganismAAtrial natriuretic peptide receptor agonistHumans",[],"['Anions', 'Antihypertensive Agents', 'Arteriolar Smooth Muscle, Agents Acting On', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cyanides', 'Direct Vasodilators', 'Drugs that are Mainly Renally Excreted', 'Electrolytes', 'Ferric Compounds', 'Ferricyanides', 'Hypotensive Agents', 'Indicators and Reagents', 'Ions', 'Iron Compounds', 'Laboratory Chemicals', 'Methemoglobinemia Associated Agents', 'Nitrates and Nitrites', 'Nitric Oxide Donors', 'Nitroferricyanide Derivatives', 'Nitrogen Compounds', 'Vasodilating Agents', 'Vasodilation']" +DB12455,Omadacycline,Omadacyclineis a tetracycline antibiotic used to treat community acquired bacterial pneumonia.,"['P0A7V3', 'P02359', 'P0A7W7', 'P0A7U3', 'P0AG59']","Omadacycline can be either bacteriostatic or bacteriocidal depending on the organism involved.1,3It disrupts bacterial protein synthesis without affecting DNA, RNA, or peptidoglycan synthesis. Omadacycline represents an improvement over existing tetracycline agents as it has not been found to be subject to tetracycline resistance mediated by tetracycline efflux pumps encoded by the tet(K), tet(L), and tet(B) or to ribosomal protection proteins encoded by tet(O) and tet(M).Label,1,2Omadacycline is susceptible to RNA mutations which confer resistance to tetracyclines.4",[H][C@@]12CC3=C(C=C(CNCC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2)N(C)C,"Omadacycline binds to the primary tetracycline binding site on the bacterial s ribosomal subunit with high specificity.There it acts to block protein synthesis, disrupting many facets of cellular function and resulting in either cell death or stasis.,,TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal RNAinhibitorEnteric bacteria and other eubacteria",[],"['Anti-Bacterial Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Naphthacenes', 'P-glycoprotein substrates', 'Tetracyclines']" +DB00359,Sulfadiazine,"Sulfadiazineis a sulfonamide antibiotic used in a variety of infections, such as urinary tract infections, trachoma, and chancroid.",['Q27738'],"Sulfadiazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors ofp-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.",NC1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=N1,Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.TargetActionsOrganismADihydropteroate synthetaseinhibitorPlasmodium falciparum,[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Antiparasitic Agents', 'Antiprotozoals', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Coccidiostats', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Intermediate-Acting Antibacterial Sulfonamides', 'Methemoglobinemia Associated Agents', 'Sulfanilamides', 'Sulfonamide Antibacterial', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds']" +DB09462,Glycerin,A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism.,"['Q03181', 'Q03181', 'Q9NZK7', 'Q9NPH2', 'P00325', 'Q14643', 'P09466', 'P17050', 'P84077', 'O43252', 'P23367', 'P69924', 'P17802', 'O14717', 'O43708']",Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.,OCC(O)CO,"When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. +Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream.TargetActionsOrganismAPeroxisome proliferator-activated receptor deltaagonistHumansUGroup IIE secretory phospholipase ANot AvailableHumansUInositol--phosphate synthase Not AvailableHumansUAlcohol dehydrogenase BNot AvailableHumansUInositol ,,-trisphosphate receptor type Not AvailableHumansUGlycodelinNot AvailableHumansUAlpha-N-acetylgalactosaminidaseNot AvailableHumansUADP-ribosylation factor Not AvailableHumansUBifunctional '-phosphoadenosine '-phosphosulfate synthase Not AvailableHumansUDNA mismatch repair protein MutLNot AvailableEscherichia coli (strain K)URibonucleoside-diphosphate reductase subunit betaNot AvailableEscherichia coli (strain K)UA/G-specific adenine glycosylaseNot AvailableEscherichia coli (strain K)UtRNA (cytosine()-C())-methyltransferaseNot AvailableHumansUMaleylacetoacetate isomeraseNot AvailableHumans","['Bowel preparation therapy', 'Topical Antisepsis', 'Skin protection']","['Alcohols', 'Alimentary Tract and Metabolism', 'Basic Ointments and Protectants', 'Carbohydrates', 'Cell-mediated Immunity', 'Compounds used in a research, industrial, or household setting', 'Cryoprotective Agents', 'Cytochrome P-450 CYP2E1 Inducers', 'Cytochrome P-450 CYP2E1 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Drugs for Constipation', 'Enemas', 'Increased Histamine Release', 'Increased IgG Production', 'Irrigating Solutions', 'Laxatives', 'Non-Standardized Chemical Allergen', 'Osmotic Laxatives', 'Other Cold and Cough Preparations', 'Other Diagnostics', 'Protective Agents', 'Solvents', 'Sugar Alcohols', 'Triose Sugar Alcohols']" +DB01241,Gemfibrozil,Gemfibrozilis a lipid regulator that is used in the reduction of serum triglyceride levels in high-risk patients with hyperlipidemia.,"['Q07869', 'Q9Y6L6', 'Q8TCC7', 'O94956', 'Q9NPD5']","Gemfibrozil alters lipid metabolism to treat patients with hyperlipidemia.11The duration of action requires twice daily dosing as the mean residence time of gemfibrozil is up to 9.6h in patients with chronic renal failure.7Gemfibrozil has a wide therapeutic index as trials with twice the standard dose were not associated with severe side effects.8,11Patients taking gemfibrozil may be at an increased risk of developing cholelithiasis and cholecystitis, as seen in patients takingclofibrate.11",CC1=CC(OCCCC(C)(C)C(O)=O)=C(C)C=C1,"Gemfibrozil activates peroxisome proliferator-activated receptor-α (PPARα), which alters lipid metabolism.This activation leads to increased HDL, apo AI, apo AII, lipoprotein lipase (LPL), inhibition of apo B synthesis, peripheral lipolysis, decreased removal of free fatty acids by the liver, and increased clearance of apoB.,,Upregulated LPL reduces plasma triglyceride levels.,,Decreased hepatic removal of fatty acids decreases the production of triglycerides.,,The effects on apoB synthesis and clearance decrease VLDL production which also reduce plasma triglyceride levels.,,Gemfibrozil's glucuronide metabolite is also an inhibitor of CYPC.TargetActionsOrganismAPeroxisome proliferator-activated receptor alphaagonistHumansUSolute carrier organic anion transporter family member BinhibitorHumansUSolute carrier family member inhibitorHumansUSolute carrier organic anion transporter family member BinhibitorHumansUSolute carrier organic anion transporter family member BinhibitorHumans",[],"['Acids, Acyclic', 'Agents Causing Muscle Toxicity', 'Benzene Derivatives', 'Butyrates', 'Chemically-Induced Disorders', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Ethers', 'Fatty Acids', 'Fatty Acids, Volatile', 'Fibric Acid Derivatives', 'Fibric Acids', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Isobutyrates', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Lipids', 'Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia', 'Noxae', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Pentanoic Acids', 'Peroxisome Proliferator Receptor alpha Agonist', 'Peroxisome Proliferator-activated Receptor alpha Agonists', 'Phenols', 'Phenyl Ethers', 'Photosensitizing Agents', 'Toxic Actions', 'UGT1A1 Inhibitors', 'UGT1A1 Substrates', 'UGT1A3 Inhibitors', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B17 substrates', 'UGT2B7 substrates', 'Valerates']" +DB00745,Modafinil,"Modafinilis a stimulant used to improve wakefulness in patients with sleep apnea, narcolepsy, or shift work disorder.","['Q01959', 'P35368']","Modafinil is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by modafinil. The prexin neuron activation is associated with psychoactivation and euphoria. Modafinil is not indicated for complaints of lack of energy or fatigue; but it appears to be very helpful for some patients. Also, it has been used in the treatment of hypersomnia, a disorder in which patients lack the capacity for meaningful sleep and may require ten or more hours per day. Recent studies have have found that modafinil may help recovering cocaine addicts fight their addiction.",NC(=O)CS(=O)C(C1=CC=CC=C1)C1=CC=CC=C1,"The exact mechanism of action is unclear, althoughin vitrostudies have shown it to inhibit the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Modafinil activates glutamatergic circuits while inhibiting GABA. Modafinil is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects. It is possible that modafinil acts by a synergistic combination of mechanisms including direct inhibition of dopamine reuptake, indirect inhibition of noradrenalin reuptake in the VLPO and orexin activation. Modafinil has partial alpha B-adrenergic agonist effects by directly stimulating the receptors.TargetActionsOrganismASodium-dependent dopamine transporterinhibitorHumansUAlpha-B adrenergic receptorpartial agonistHumans",[],"['Benzene Derivatives', 'Benzhydryl Compounds', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Centrally Acting Sympathomimetics', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (moderate)', 'Cytochrome P-450 CYP3A5 Inducers (weak)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Increased Sympathetic Activity', 'Nervous System', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Stimulants', 'Sympathomimetic-like Agent', 'Wakefulness-Promoting Agents']" +DB00557,Hydroxyzine,"Hydroxyzineis an antihistamine used to treat anxiety and tension associated with psychoneuroses, as well as allergic conditions such as pruritus and chronic urticaria.","['P35367', 'Q12809']","Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus.18Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states.15Hydroxyzine is relatively fast-acting, with an onset of effect that occurs between 15 and 60 minutes and a duration of action between 4-6 hours.2Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia - patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required.18Hydroxyzine is reported to prolong the QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation.15,10",OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1,"The Hhistamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, Hreceptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.Hydroxyzine is a potent inverse agonist of histamine H-receptors- inverse agonists are agents that are considered to have a ""negative efficacy"", so rather than simply blocking activity at a receptor they actively dampen its activity.Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus.Hydroxyzine is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS.These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets.TargetActionsOrganismAHistamine H receptorinverse agonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Anti-Anxiety Agents', 'Antipruritics', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Diphenylmethane Derivatives', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine Receptor Antagonists', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Piperazines', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'QTc Prolonging Agents']" +DB00349,Clobazam,Clobazamis a benzodiazepine used as adjunct treatment in seizures associated with Lennox-Gastaut syndrome.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Clobazam belongs to the benzodiazepine class of drugs.23Clobazam acts on the GABAAreceptor to increase GABAnergic transmission, particularly chloride conductance in neurons.9This causes neuronal hyperpolarization, resulting in an increase in the action potential threshold and reducing neuron firing frequency.11,12Consequently, the general neuronal activity of the central nervous system is depressed; therefore, clobazam can be used to treat diseases caused by excessive excitatory action potentials.12The effect of clobazam 20 mg and 80 mg administered twice daily on QTc interval was evaluated in a randomized, evaluator-blinded, placebo-, and active-controlled (moxifloxacin 400 mg) parallel thorough QT study in 280 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on the Fridericia correction method was below 10 ms, the threshold for regulatory concern. +Thus, at a dose two times the maximum recommended dose, clobazam did not prolong the QTc interval to any clinically relevant extent.23",CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O,"The exact mechanism of action for clobazam, a ,-benzodiazepine, is not fully understood but is thought to involve the potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAAreceptor.Specifically, clobazam binds to the interface of the αand γ-subunit of the GABAAreceptor.It has a great affinity for the αsubunit than the αsubunit compared to other ,‐benzodiazepines.Binding of clobazam to the GABAAreceptor causes chloride channels to open, resulting in an influx of chloride and thus hyperpolarization of neurons.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Anticonvulsants', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Agonists', 'GABA-A Receptor Agonists', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'UGT1A4 Inhibitors', 'UGT1A6 Inhibitors']" +DB08815,Lurasidone,Lurasidoneis an atypical antipsychotic used to treat schizophrenia and depressive episodes associated with bipolar I disorder.,"['P14416', 'P28223', 'P34969', 'P08908', 'P18825', 'P08913']","Lurasidone is a benzothiazol derivative that is an antagonist and binds with high affinity to Dopamine-2 (D2) (Ki = 0.994 nM), 5-HT2A (Ki = 0.47 nM) receptors, and 5-HT7 receptors (Ki = 0.495 nM). It also binds with moderate affinity to alpha-2C adrenergic receptors (Ki = 10.8 nM) and is a partial agonist at 5-HT1A receptors (Ki = 6.38 nM). Its actions on histaminergic and muscarinic receptors are negligible.",[H][C@@]12[C@H]3CC[C@H](C3)[C@]1([H])C(=O)N(C[C@@H]1CCCC[C@H]1CN1CCN(CC1)C1=NSC3=CC=CC=C13)C2=O,Lurasidone is an atypical antipsychotic that is a D and -HTA (mixed serotonin and dopamine activity) to improve cognition. It is thought that antagonism of serotonin receptors can improve negative symptoms of psychoses and reduce the extrapyramidal side effects that are often associated with typical antipsychotics.TargetActionsOrganismADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor AantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorNot AvailableHumans,[],"['Adrenergic Agents', 'Adrenergic alpha-2 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Indole Derivatives', 'Isoindoles', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thiazoles', 'Tranquilizing Agents']" +DB01224,Quetiapine,"Quetiapineis a psychotropic agent used for the management of bipolar disorder, schizophrenia, and major depressive disorder.","['P28223', 'P14416', 'P08908', 'P28222', 'P28221', 'P28566', 'P28335', 'P46098', 'P50406', 'P34969', 'P21728', 'P21918', 'P35462', 'P21917', 'P35367', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Quetiapine improves the positive and negative symptoms of schizophrenia and major depression by acting on various neurotransmitter receptors, such as the serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms.1,8,9A note on suicidality in young patients and administration in the elderlyQuetiapine can cause suicidal thinking or behavior in children and adolescents and should not be given to children under 10 years of age. It is important to monitor for suicidality if this drug is given to younger patients. In addition, this drug is not indicated for the treatment of psychosis related to dementia due to an increased death rate in elderly patients taking this drug.19",OCCOCCN1CCN(CC1)C1=NC2=CC=CC=C2SC2=CC=CC=C12,"Although the mechanism of action of quetiapine is not fully understood, several proposed mechanisms exist. In schizophrenia, its actions could occur from the antagonism of dopamine type (D) and serotonin A (HTA) receptors. In bipolar depression and major depression, quetiapine's actions may be attributed to the binding of this drug or its metabolite to the norepinephrine transporter. Additional effects of quetiapine, including somnolence, orthostatic hypotension, and anticholinergic effects, may result from the antagonism of H receptors, adrenergic α receptors, and muscarinic M receptors, respectively.,,TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansU-hydroxytryptamine receptor Aantagonistpartial agonistHumansU-hydroxytryptamine receptor BligandHumansU-hydroxytryptamine receptor DligandHumansU-hydroxytryptamine receptor EligandHumansU-hydroxytryptamine receptor CligandHumansU-hydroxytryptamine receptor AligandHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor ligandHumansUDopamine D receptorantagonistHumansUDopamine D receptorligandHumansUDopamine D receptorligandHumansUDopamine D receptorligandHumansUHistamine H receptorantagonistHumansUAlpha- adrenergic receptorsantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MligandHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MligandHumansUMuscarinic acetylcholine receptor MligandHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Azepines', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Diazepines, Oxazepines, Thiazepines and Oxepines', 'Dibenzothiazepines', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Nervous System', 'P-glycoprotein substrates', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Thiazepines', 'Thiepins', 'Tranquilizing Agents']" +DB00985,Dimenhydrinate,"Dimenhydrinateis a medication used to prevent and treat nausea, vomiting, vertigo, and motion sickness.",['P35367'],"Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness.9,10It has a short duration of action of 4-8 hours.4Patients should be counselled regarding pronounced drowsiness, avoiding alcohol and other sedatives, and exercising caution when operating a motor vehicle or heavy machinery.9",CN1C2=C(N=C(Cl)N2)C(=O)N(C)C1=O.CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1,"Dimenhydrinate is a theoclate salt that separates intodiphenhydramineand-chlorotheophylline.,While the exact mechanism of action is unknown, diphenhydramine is theorized to reduce disturbances to equilibrium through antimuscarinic effects or histamine H antagonism.-chlorotheophylline may produce excitation through blocking adenosine receptors, reducing the drowsiness produced by diphenhydramine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Alkaloids', 'Amines', 'Aminoalkyl Ethers', 'Antiemetics', 'Antihistamines for Systemic Use', 'Autonomic Agents', 'Benzene Derivatives', 'Benzhydryl Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Ethanolamine Derivatives', 'Ethylamines', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Pharmaceutical Preparations', 'Purines', 'Purinones', 'QTc Prolonging Agents']" +DB01558,Bromazepam,Bromazepamis a short-acting benzodiazepine with intermediate onset commonly used to treat panic disorders and severe anxiety.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Bromazepam is a lipophilic, long-acting benzodiazepine and with sedative, hypnotic, anxiolytic and skeletal muscle relaxant properties. It does not possess any antidepressant qualities. Bromazepam, like other benzodiazepines, presents a risk of abuse, misuse, and dependence. According to many psychiatric experts, Bromazepam has a greater abuse potential than other benzodiazepines because of fast resorption and rapid onset of action.",BrC1=CC2=C(NC(=O)CN=C2C2=CC=CC=N2)C=C1,Bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects. Other neurotransmitters are not influenced.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans,[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB01063,Acetophenazine,Acetophenazine is an antipsychotic drug of moderate-potency. It is used in the treatment of disorganized and psychotic thinking. It is also used to help treat false perceptions (e.g. hallucinations or delusions). It primarily targets the dopamine D2 receptor.,"['P14416', 'P10275']",Acetophenzine is a phenothiazine antipsychotic intended for the management of schizophrenia and other psychotic disorders.,CC(=O)C1=CC=C2SC3=C(C=CC=C3)N(CCCN3CCN(CCO)CC3)C2=C1,"Acetophenazine blocks postsynaptic mesolimbic dopaminergic D and D receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.TargetActionsOrganismADopamine D receptorantagonistHumansUAndrogen receptorNot AvailableHumans",[],"['Antipsychotic Agents', 'Central Nervous System Depressants', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Phenothiazines', 'Phenothiazines With Piperazine Structure', 'Psycholeptics', 'Sulfur Compounds']" +DB04896,Milnacipran,Milnacipranis a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of fibromyalgia and a short-term treatment of major depressive disorder.,"['P31645', 'P23975', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391']","When utilized to treat fibromyalgia, the effect of milnacipran on the QTcF interval in patients was measured in a double-blind placebo-and positive-controlled parallel study in 88 healthy subjects using three to six times the recommended therapeutic dose for fibromyalgia at 600 mg/day26. After baseline and placebo adjustment, the maximum mean QTcF change was 8 ms - an increase that is generally not considered to be clinically significant26.Conversely, when used for treating major depressive disorder (MDD), non-clinical studies have shown that levomilnacipran binds with high affinity to the norepinephrine (NE) and serotonin (5-HT) transporters (Ki = 71-91 nM and 11 nM respectively at human transporters)24,25,26. Levomilnacipran inhibits the uptake of both NE and 5-HT in vitro and in vivo; preferentially inhibiting reuptake of NE over 5-HT by approximately 2-fold24,25,26. Levomilnacipran does not directly affect the uptake of dopamine or other neurotransmitters24,25,26. Levomilnacipran has no significant affinity for serotonergic (5-HT1-7), α- and β-adrenergic, muscarinic (M1-5), histamine (H1-4), dopamine (D1-5), opiate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors in vitro24,25. Levomilnacipran has no significant affinity for Ca++, K+, Na+, and Cl– channels and does not inhibit the activity of human monoamine oxidases (MAO-A and MAO-B) or acetylcholinesterase24,25,26.Moreover, in ECG studies with levomilnacipran used to treat MDD, although no clinically significant changes in QTcF interval (QTcF=QT/RR0.33) were noted, it appears that the agent can cause increases in heart rate and blood pressure24. In particular, it appears that the maximum therapeutic dose of levomilnacipran at 120 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 20.2 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 3.8 to 7.2 mmHg and 6.1 to 8.1 mmHg, respectively24. Alternatively, a supratherapeutic dose of 300 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 22.1 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 5.4 to 7.9 mmHg and 7.9 to 10.6 mmHg, respectively24.",CCN(CC)C(=O)C1(CC1CN)C1=CC=CC=C1,"The dual ability for milnacipran to inhibit the reuptake of both serotonin (HT) and norepinephrine (NE) facilitates its treatment of both fibromyalgia and major depressive disorder (MDD).In particular, it is generally believed that HT and NE participate in the modulation of endogenous analgesic mechanisms by way of the descending inhibitory pain pathways in the brain and spinal cord,,. Although the specific mechanism of action remains unclear, some studies have proposed that low levels of HT may be associated with increased sensitivity to pain - a condition that could subsequently be improved by milnacipran's capacity to enhance the presence of HT by inhibiting its reuptake via serotonin transporters at synaptic clefts,,. Furthermore, in the CNS it is also generally believed that NE released from descending pathways can mitigate pain sensations via eliciting inhibitory effects on alpha-A-adrenoceptors on central terminals of primary afferent nociceptors, by direct alpha--adrenergic action on pain-relay neurons, and by alpha--adrenoceptor-mediated activation of inhibitory interneurons. Such NE pain mitigation is consequently also enhanced by milnacipran's ability to enhance the presence of NE by inhibiting its reuptake via norepinephrine transporters at synaptic clefts.Concurrently, milnacipran's capacity to inhibit the reuptake of both HT and NE also facilitates its treatment of MDD. Given the monoamine hypothesis' assertion that decreased HT can be associated with anxiety, obsessions, compulsions, and decreased NE can result in lowered alertness, energy, attention, and general interest in life, it is proposed that milnacipran's basic activities as a serotonin and norepinephrine reuptake inhibitor could assist in treating such symptoms of MDD by increasing the presence of both HT and NE in the body by inhibiting their reuptake.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumansUNMDA receptorinhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Analgesics', 'Analgesics, Non-Narcotic', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cyclopropanes', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Uptake Inhibitors', 'Peripheral Nervous System Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin and Noradrenaline Reuptake Inhibitors', 'Serotonin Modulators']" +DB06700,Desvenlafaxine,Desvenlafaxineis an antidepressant agent and SNRI used for the treatment of major depressive disorders in adults.,"['P23975', 'P31645', 'Q01959']","Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor.3,4,12It lacks significant activity on muscarinic-cholinergic, H1-histaminergic, or α1-adrenergic receptorsin vitro, or inhibitory activity against monoamine oxidase.12Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity.4It was also shown to lack significant activity against the cardiac potassium channel, hERG,in vitro.6Electrocardiograms were obtained from 1,492 desvenlafaxine treated patients with major depressive disorder and 984 placebo-treated patients in clinical studies lasting up to 8 weeks. No clinically relevant differences were observed between desvenlafaxine treated and placebo-treated patients for QT, QTc, PR, and QRS intervals. In a thorough QTc study with prospectively determined criteria, desvenlafaxine did not cause QT prolongation. No difference was observed between placebo and desvenlafaxine treatments for the QRS interval.12",CN(C)CC(C1=CC=C(O)C=C1)C1(O)CCCCC1,"The exact mechanism of the antidepressant action of desvenlafaxine is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake.Particularly, desvenlafaxine has been found to inhibit the serotonin, norepinephrine, and dopamine transporters with varying degrees of affinity. Desvenlafaxine inhibits serotonin transporters with times the affinity of norepinephrine transporters, and dopamine transporters with the lowest affinity.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Agents that reduce seizure threshold', 'Alcohols', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Benzene Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cyclohexanes', 'Cyclohexanols', 'Cycloparaffins', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fatty Alcohols', 'Hexanols', 'Hypoglycemia-Associated Agents', 'Lipids', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Uptake Inhibitors', 'Phenols', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin and Noradrenaline Reuptake Inhibitors', 'Serotonin Modulators', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT2B17 substrates']" +DB01255,Lisdexamfetamine,Lisdexamfetamineis a central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) and moderate to severe eating disorders.,['Q96RJ0'],"Once administered, lisdexamfetamine is converted to its active metabolite, dextroamphetamine, which is taken up by the brain. Dextroamphetamine blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.6",C[C@@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CCCCN,"Lisdexamfetamine is a prodrug of dextroamphetamine, which is a noncatecholamine sympathomimetic amine with CNS stimulant activity. Dextroamphetamine is a known inhibitor of the dopamine transporter (DAT), noradrenaline transporter (NET) and vesicular monoamine transporter (VMAT), with a weaker affinity for the serotonin transporter (SERT). It is also a weak monoamine oxidase (MAO) inhibitor.Dextroamphetamine ultimately blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases catecholamine availability in the extracellular space.The exact mode of therapeutic action of lisdexamfetamine in ADHD and BED has not been fully elucidated; however, the clinical effects of lisdexamfetamine are believed to be linked to the pharmacological actions of dextroamphetamine.,TargetActionsOrganismUTrace amine-associated receptor agonistHumans",[],"['Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Amphetamines', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Central Nervous System Stimulation', 'Centrally Acting Sympathomimetics', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Ethylamines', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Phenethylamines', 'Psychoanaleptics', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetics']" +DB00191,Phentermine,Phentermineis a sympathomimetic anorectic agent used as a short-term adjunct therapy that is included in a regimen of weight reduction in cases of exogenous obesity.,"['P23975', 'P31645', 'Q01959', 'P21397', 'P27338', 'P01303']","It is reported that the main mechanism of action of phentermine is the generation of appetite suppression, maybe due to the increase in leptin, but it is considered that other mechanisms should be involved.4Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure.3In clinical studies where phentermine was used as a monotherapy and as combination therapy, this drug has shown an average weight loss of 3.6 kg when compared with the placebo in 2-24 weeks. Patients treated with phentermine also showed increased maintenance of the weight after treatment discontinuation.3As well, even though it is a derivative of the amphetamines, it has not been registered to produce any of the effects of amphetamine such as central nervous system stimulation, elevation of blood pressure, tachyphylaxis or QTc prolongation.4",CC(C)(N)CC1=CC=CC=C1,"Phentermine is an indirect-acting sympathomimetic agent that acts by releasing noradrenaline from the presynaptic vesicles in the lateral hypothalamus. This increase in noradrenaline concentration in the synaptic cleft results in the stimulation of beta-adrenergic receptors.Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin.Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger.This combined effect produces a continuous flight-or-fight response in the body which reduces the hunger signal as this state is on the immediate need for energy.Lastly, some reports have indicated that phentermine is a weak inhibitor of monoamine oxidase but this mechanism does not tend to produce a clinically significant response.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansASodium-dependent dopamine transporterinhibitorHumansAAmine oxidase [flavin-containing] AantagonistHumansAAmine oxidase [flavin-containing] BantagonistHumansAPro-neuropeptide YinhibitorHumans",['Chronic Weight Management therapy'],"['Adrenergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Amines', 'Amphetamines', 'Anti-Obesity Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Appetite Depressants', 'Appetite Suppression', 'Autonomic Agents', 'Central Nervous System Agents', 'Centrally Acting Antiobesity Products', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Increased Sympathetic Activity', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sympathomimetic Amine Anorectic', 'Sympathomimetics']" +DB01059,Norfloxacin,Norfloxacinis a broad-spectrum fluoroquinolone antibiotic with variable activity against gram-positive and gram-negative bacteria. Typically reserved for the treatment of UTIs due to accumulation in the urine.,"['P43700', 'P43702', 'P11388', 'P20831', 'P11388', 'Q02880', 'P0C1U9']","Norfloxacin is a quinolone/fluoroquinolone antibiotic. Norfloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian.",CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCNCC1,"The bactericidal action of Norfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. Norfloxacin is a broad-spectrum antibiotic agent that is shown to be effective against various Gram-positive and Gram-negative bacterial species. The fluorine atom at the position increases potency against gram-negative organisms, and the piperazine moiety at the position is responsible for anti-pseudomonal activityTargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumansUDNA gyrase subunit AinhibitorStaphylococcus aureusUDNA topoisomerase inhibitorHumansUDNA topoisomerase subunit AinhibitorStaphylococcus aureus",[],"['Agents Causing Muscle Toxicity', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'OAT1/SLC22A6 inhibitors', 'Ophthalmologicals', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Sensory Organs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01262,Decitabine,Decitabineis a chemotherapeutic pyrimidine nucleoside analogue used for the treatment of myelodysplastic syndromes (MDS) by inducing DNA hypomethylation and corresponding alterations in gene expression.,"['P26358', 'Q9Y6K1', 'Q9UBC3', 'Q13547', 'Q969S8', 'Q96DB2', 'Q92769', 'O15379', 'P56524', 'Q9UQL6', 'Q9UBN7', 'Q8WUI4', 'Q9BY41', 'Q9UKV0']","Decitabine is a prodrug analogue of the natural nucleotide 2’-deoxycytidine, which, upon being phosphorylated intracellularly, is incorporated into DNA and exerts numerous effects on gene expression.3,4,5,8,11The use of decitabine is associated with neutropenia and thrombocytopenia. In addition, decitabine can cause fetal harm in pregnant women; effective contraception and avoidance of pregnancy are recommended during treatment with decitabine.11",NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1,"Myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms that manifest in peripheral cytopenias and may eventually progress to secondary acute myeloid leukemia (sAML). Included in the over genes commonly mutated in MDS patients are those involved in DNA methylation and histone modification, and it is well-established that alteration of the epigenetic landscape is a feature of myeloid leukemias.,Decitabine is considered a prodrug, as it requires transport into cells and subsequent phosphorylation by distinct kinases to generate the active molecule -aza-'-deoxycytidine-triphosphate, which is incorporated by DNA polymerase during DNA replication.,,,,,Once incorporated into DNA, decitabine is recognized as a substrate by DNA methyltransferase enzymes (DNMTs), specifically DNMT, but due to the presence of an N rather than C atom, traps the DNMT through the irreversible formation of a covalent bond.,At low concentrations, this mode of action depletes DNMTs and results in global DNA hypomethylation while at high concentrations, it additionally results in double-strand breaks and cell death.,,The general hypothesis regarding decitabine's therapeutic efficacy is that the global hypomethylation it induces results in the expression of previously silent tumour suppressor genes.,,,,,,,,However, there are other putative mechanisms also related to this change in DNA methylation, including indirect alteration of transcription through effects on transcription factors, indirectly altering histone modifications and chromatin structure, and activating pathways involved in DNA damage response.,,,The overall effect of decitabine is a decrease in neoplastic cell proliferation and an increase in the expression of tumour suppressor genes.TargetActionsOrganismADNAother/unknownHumansADNA (cytosine-)-methyltransferase inhibitorHumansUDNA (cytosine-)-methyltransferase AinhibitorHumansUDNA (cytosine-)-methyltransferase BinhibitorHumansUHistone deacetylaseinhibitorHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Aza Compounds', 'Carbohydrates', 'Cytidine Deaminase Substrates', 'Enzyme Inhibitors', 'Glycosides', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'Pyrimidine Analogues', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Ribonucleosides', 'Toxic Actions']" +DB00490,Buspirone,Buspironeis an anxiolytic agent used for short-term treatment of generalized anxiety and second-line treatment of depression.,"['P08908', 'P14416', 'P35462', 'P21917', 'P35348', 'P35368', 'P25100']","The clinical effect of buspirone in alleviating the symptoms of generalized anxiety disorders typically takes 2 to 4 weeks to achieve.10The delayed onset of action of buspirone suggests that the therapeutic effectiveness in generalized anxiety may involved more than its molecular mechanism of action at the 5-HT1Areceptors,9or buspirone may induce adaptations of 5-HT1Areceptors.10Buspirone was not shown to alter the psychomotor or cognitive function in healthy volunteers, and the risk of developing sedation is relatively low compared to other anxiolytics, such as benzodiazepines.1Unlike benzodiazepines and barbiturates used in anxiety disorders, buspirone is not associated with a risk for developing physical dependence or withdrawal, or any significant interaction with central nervous system depressants such as ethanol. This is due to the lack of effects on GABA receptors.1,10Buspirone also does not exhibit any anticonvulsant or muscle-relaxing properties,5but may interfere with arousal reactions due to its inhibitory action on the aactivity of noradrenergic locus coerulus neurons.9Despite its clinical effectiveness in generalized anxiety, buspirone demonstrated limited clinical effectiveness on panic disorders, severe anxiety, phobias, and obsessive compulsive disorders.4,9The clinical effectiveness of the long-term use of buspirone, for more than 3 to 4 weeks, has not demonstrated in controlled trials but there were no observable significant adverse events in patients receiving buspirone for a year in a study of long-term use.13",O=C1CC2(CCCC2)CC(=O)N1CCCCN1CCN(CC1)C1=NC=CC=N1,"The therapeutic action of buspirone in generalized anxiety disorders is thought to be mainly derived from its interaction with two major -HTAreceptor subtypes that are involved in the brain's anxiety and fear circuitry to enhance the serotonergic activity in these brain areas.Buspirone acts as a full agonist at presynaptic -HTAreceptors, or -HTAautoreceptors, expressed at dorsal raphe while acting as a partial agonist at the postsynaptic -HTAreceptors expressed on hippocampus and cortex.,-HTAreceptors function as inhibitory autoreceptors by being expressed on the soma or dendrites of serotonergic neurons or mediate postsynaptic actions of -HT by being highly expressed on the corticolimbic circuits.They are inhibitory G-protein coupled receptors that couple to Gi/Go proteins. When activated, presynaptic -HTAautoreceptors causes neuron hyperpolarization and reduces the firing rate of the serotonergic neuron, thereby decreasing extracellular -HT levels in the neuron's projection areas. Activated postsynaptic -HTAreceptors promote hyperpolarization to released -HT on pyramidal neurons.The anxiolytic action of buspirone is mainly thought to arise from the interaction at presynaptic -HTAautoreceptors. Acting as a potent agonist in these receptors, buspirone initially causes activation of these autoreceptors and inhibition of -HT release. It is proposed that buspirone induces desensitization of somatodendritic autoreceptors over time, which may explain the delayed onset of action of the drug. Desensitization of the autoreceptors ultimately results in heightened excitation of serotonergic neurons and enhanced -HT release.Buspirone also displays a weak affinity for serotonin HT receptors and acts as a weak antagonist on dopamine D autoreceptors,although there is not much evidence that the action at these receptors contribute to the anxiolytic effect of buspirone.It acts as an antagonist at presynaptic dopamine D and D receptors and may bind to alpha- adrenergic receptors as a partial agonist.TargetActionsOrganismA-hydroxytryptamine receptor Apartial agonistHumansADopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUAlpha- adrenergic receptorspartial agonistHumans",[],"['Agents that produce hypertension', 'Antidepressive Agents', 'Azaspirodecanedione Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Piperazines', 'Psycholeptics', 'Pyrimidines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Spiro Compounds', 'Tranquilizing Agents']" +DB00611,Butorphanol,Butorphanolis an opioid agonist-antagonist used to treat moderate to severe pain.,"['P41145', 'P41143', 'P35372']","Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord.",[H][C@@]12CC3=C(C=C(O)C=C3)[C@]3(CCCC[C@@]13O)CCN2CC1CCC1,"The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Butorphanol is believed to have both partial agonism and partial antagonism at the μ-opioid receptor, as well as partial agonist and antagonist activity at the κ-opioid receptor.TargetActionsOrganismAKappa-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansAMu-type opioid receptorantagonistHumans",[],"['Alkaloids', 'Analgesics', 'Antitussive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Mixed Agonist / Antagonist Opioids', 'Morphinan Derivatives', 'Morphinans', 'Narcotics', 'Nervous System', 'Opiate Alkaloids', 'Opiate Partial Agonists', 'Opioid Agonist/Antagonist', 'Opioid Antagonists', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Respiratory System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB09167,Dosulepin,Dosulepinis a tricyclic antidepressant commonly used only in patients for whom alternative therapies are ineffective due to its toxicity potential.,"['P08908', 'P28223', 'P35367', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P08913', 'P18089', 'P18825', 'P35348', 'P35368', 'P25100', 'P23975', 'P31645']",Dosulepin is a tricyclic antidepressant that interacts with various receptors and transporters. It is a monoamine reuptake inhibitor with approximately equal potency for noradrenaline and 5-HT that increases the availability of these neurotransmitters at the central synapses8. The metabolites of dosulepin are shown to inhibit 5HT uptake by the human blood platelet2.,CN(C)CC\C=C1/C2=CC=CC=C2CSC2=CC=CC=C12,"By binding to noradrenaline transporter (NAT) and serotonin transporter (SERT) in an equipotent manner and inhibiting the reuptake activity, dosulepin increases the free levels of noradrenaline and HT at the synaptic cleft. It is shown that the main metabolite northiaden is a more potent inhibitor of noradrenaline uptake than the parent drug.Dosulepin displays affinity towards α-adrenoceptors and to a lesser extent, α-adrenoceptors. Inhibition of presynaptic α-adrenoceptors by dosulepin facilitates noradrenaline release and further potentiates the antidepressant effects. It also downregulates central β-adrenoceptors by causing a decline in the number of receptors and reduces noradrenaline-induced cyclic AMP formation,. +Dosulepin binds to HTA and HTA receptors in the cerebral cortex and hippocampus as an antagonist. HTA receptors are autoreceptors that inhibit HT release and HTA receptors are Gi/Go-coupled receptors that reduces dopamine release upon activation. Antagonism at HTA receptors may also improve sleep patterns. Dosulepin also binds to muscarinic acetylcholine receptors and causes antimuscarinic side effects such as dry mouth. By acting as an antagonist at histamine type (H) receptors, dosulepin mediates a sedative effect.Main metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide may also bind to HT, α and H receptors, although with less affinity compared to the parent drug.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor AantagonistHumansAHistamine H receptorantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAAlpha- adrenergic receptorsantagonistHumansAAlpha- adrenergic receptorsantagonistHumansASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents, Tricyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dibenzothiepins', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tertiary amine tricyclic antidepressants', 'Thiepins']" +DB01149,Nefazodone,Nefazodoneis an antidepressant used in the treatment of depression.,"['P28223', 'P28335', 'P31645', 'P08908', 'P23975', 'Q01959', 'P35368', 'P08913', 'P35348', 'Q12809']","Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors.",CCC1=NN(CCCN2CCN(CC2)C2=CC(Cl)=CC=C2)C(=O)N1CCOC1=CC=CC=C1,"Within the serotonergic system, nefazodone acts as an antagonist at type serotonin (-HT) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with -HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha()-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha()-adrenergic receptors is not significant.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor CantagonistHumansASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor AantagonistHumansASodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumansUAlpha-B adrenergic receptorother/unknownHumansUAlpha-A adrenergic receptorantagonistHumansNAlpha-A adrenergic receptorantagonistHumansUPotassium voltage-gated channel subfamily H member antagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Analgesics', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Second-Generation', 'Antidepressive Agents, Triazolopyridine', 'BSEP/ABCB11 Substrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'Psychoanaleptics', 'Psychotropic Drugs', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin and Noradrenaline Reuptake Inhibitors', 'Serotonin antagonist and reuptake inhibitors (SARIs)', 'Serotonin Modulators', 'Serotonin Receptor Antagonists']" +DB00690,Flurazepam,Flurazepamis a long-acting benzodiazepine with a rapid onset of action that is commonly used to treat insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Flurazepam, a benzodiazepine derivative, is a hypnotic agent which does not appear to decrease dream time as measured by rapid eye movements (REM). Furthermore, it decreases sleep latency and number of awakenings for a consequent increase in total sleep time.",CCN(CC)CCN1C2=C(C=C(Cl)C=C2)C(=NCC1=O)C1=CC=CC=C1F,"Flurazepam binds to an allosteric site on GABA-A receptors. Binding potentiates the action of GABA on GABA-A receptors by opening the chloride channel within the receptor, causing chloride influx and hyperpolarization.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB04832,Zimelidine,"Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome and due to a peculiar hypersensitivity reaction involving many organs including skin exanthema, flu-like symptoms, arthralgias, and sometimes eosinophilia. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients.","['P27338', 'P21397', 'P31645']","Zimelidine was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants.",CN(C)C\C=C(\C1=CC=C(Br)C=C1)C1=CC=CN=C1,"The antidepressant actions of zimelidine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Zimelidine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on HTA autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.TargetActionsOrganismUAmine oxidase [flavin-containing] BinhibitorHumansUAmine oxidase [flavin-containing] AinhibitorHumansUSodium-dependent serotonin transporterNot AvailableHumans",[],"['Antidepressive Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'P-glycoprotein inhibitors', 'Psychoanaleptics', 'Pyridines', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01191,Dexfenfluramine,"Dexfenfluramine, also marketed under the name Redux, is a serotoninergic anorectic drug. For a fairly limited time during the middle of the nineties, the US FDA had approved it for use in managing weight loss. However, following multiple concerns about the cardiovascular side-effects of the drug, such approval was withdrawn.","['P31645', 'P28335']","Used to treat diabetes and obesity, Dexfenfluramine decreases caloric intake by increasing serotonin levels in the brain’s synapses. Dexfenfluramine acts as a serotonin reuptake inhibitor. It also causes release of serotonin from the synaptosomes.",CCN[C@@H](C)CC1=CC=CC(=C1)C(F)(F)F,Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin reuptake. The increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansU-hydroxytryptamine receptor CagonistHumans,[],"['Alimentary Tract and Metabolism', 'Amines', 'Antidepressive Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ethylamines', 'Neurotransmitter Agents', 'Phenethylamines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents']" +DB00245,Benzatropine,"Benzatropineis an anticholinergic drug used to treat Parkinson's disease (PD) and extrapyramidal symptoms, except tardive dyskinesia.","['P11229', 'Q01959', 'P35367', 'P31645', 'P23975']",The inhibition of dopamine reuptake by benztropine produces a dose-dependent increase of dopamine in the nerve terminal of the dopaminergic system.5Clinically the activity of benztropine is observed after 1-2 hours of oral administration and after a few minutes of intramuscular administration with a last-longing effect of about 24 hours. Reports have indicated that benztropine has a very large sedative effect.5The antihistaminic effect of benztropine is very similar to the effect found inpyrilamineand the anticholinergic activity was found to be equal toatropineex vivoand of about 50% activityin vivo.12,[H][C@]12CC[C@]([H])(C[C@@]([H])(C1)OC(C1=CC=CC=C1)C1=CC=CC=C1)N2C,"Benztropine is an agent with anti-muscarinic and antihistaminic effects. Its main mechanism of action is presented by the selective inhibition of dopamine transporters but it also presents affinity for histamine and muscarine receptors.It is widely known that benztropine is a potent inhibitor of presynaptic carrier-mediated dopamine transport. As well, it is known to be an analog of atropine and hence, it has a large affinity for muscarinic receptors M in the human brain. Once bound, benztropine blocks the activity of the muscarinic receptors mainly in the striatum.The increased advantage of benztropine lays on the antagonism of acetylcholine activity which corrects the imbalance between dopamine and acetylcholine in Parkinson patients.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansASodium-dependent dopamine transporterinhibitorHumansUHistamine H receptorantagonistHumansNSodium-dependent serotonin transporterinhibitorHumansNSodium-dependent noradrenaline transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Alkaloids', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Aza Compounds', 'Central Nervous System Agents', 'Cholinergic Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Ethers of Tropine or Tropine Derivatives', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine Receptor Antagonists', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Tropanes']" +DB14539,Hydrocortisone acetate,Hydrocortisone acetateis a corticosteroid used to treat inflammatory and pruritic corticosteroid-responsive dermatoses and ulcerative colitis.,"['P04083', 'P04150', 'P80365', 'P14060']","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.",[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin- (annexin-) synthesis, which then binds to cell membranes preventing the phospholipase A from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX- and COX-) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin- escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.TargetActionsOrganismAAnnexin ANot AvailableHumansAGlucocorticoid receptorNot AvailableHumansUCorticosteroid -beta-dehydrogenase isozyme Not AvailableHumansU beta-hydroxysteroid dehydrogenase/Delta -->-isomerase type Not AvailableHumans",['Postoperative Eye Care'],"['11-Hydroxycorticosteroids', '17-Hydroxycorticosteroids', 'Adrenal Cortex Hormones', 'Aerosols', 'Anti-Inflammatory Agents', 'Corticosteroids', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydrocortisone and derivatives', 'Hydroxycorticosteroids', 'Immunosuppressive Agents', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Steroids']" +DB01186,Pergolide,"Pergolideis a long-acting dopamine agonist that is uncommonly used for the management of Parkinson's disease, due to the risk for cardiac valvulopathy.","['P14416', 'P35462', 'P21917', 'P21918', 'P21728', 'P08908', 'P41595', 'P28223', 'P28221', 'P08913', 'P18089', 'P18825', 'P28222', 'P28335', 'P35348', 'P35368', 'P25100']","Pergolide stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1and D5subreceptors and are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3and D4subreceptors and has been associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2and D3receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits agonist activity on dopamine D4, D1, and D5, 5-hydroxytryptamine (5-HT)1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, α2A-, α2B-, α2C-, α1A-, α1B-, and α1D-adrenergic receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2Aagonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion. Pergolide also causes transient increases in somatotropin (growth hormone) secretion and decreases in luteinizing hormone (LH) concentrations.",[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@@H](CSC)CN2CCC,"The dopamine Dreceptor is a -transmembrane G-protein coupled receptor associated with Giproteins. In lactotrophs, stimulation of dopamine Dreceptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP-dependent release of Ca+from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p/p MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine Dreceptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor DagonistHumansUAlpha- adrenergic receptorsagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor CagonistHumansUAlpha-A adrenergic receptoragonistHumansUAlpha-B adrenergic receptoragonistHumansUAlpha-D adrenergic receptoragonistHumans",[],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alkaloids', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dopamine Agents', 'Dopamine Agonists', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Ergot-derivative Dopamine Receptor Agonists', 'Ergot-derived Dopamine Receptor Agonist', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists']" +DB01039,Fenofibrate,"Fenofibrateis a peroxisome proliferator receptor alpha activator used to lower LDL-C, total-C, triglycerides, and Apo B, while increasing HDL-C in hypercholesterolemia, dyslipidemia, and hypertriglyceridemia.","['Q07869', 'O75469', 'Q9NPA2']","Fenofibrate is a fibrate that activates peroxisome proliferator activated receptor alpha (PPARα) to alter lipid metabolism and treat primary hypercholesterolemia, mixed dyslipidemia, and severe hypertriglyceridemia.8,11,12Fenofibrate requires once daily dosing and has a half life of 19-27 hours so its duration of action is long.3,11,12Fenofibrate capsules are given at a dose of 50-150mg daily so the therapeutic index is wide.12Patients should be counselled about the risk of rhabdomyolysis, myopathy, and cholelithiasis when taking fibrates.11,12",CC(C)OC(=O)C(C)(C)OC1=CC=C(C=C1)C(=O)C1=CC=C(Cl)C=C1,"Fenofibrate activates peroxisome proliferator activated receptor alpha (PPARα), increasing lipolysis, activating lipoprotein lipase, and reducing apoprotein C-III.,,PPARα is a nuclear receptor and its activation alters lipid, glucose, and amino acid homeostasis.Activation of PPARα activates transcription of gene transcription and translation that generates peroxisomes filled with hydrogen peroxide, reactive oxygen species, and hydroxyl radicals that also participate in lipolysis.This mechanism of increased lipid metabolism is also associated with increased oxidative stress on the liver.In rare cases this stress can lead to cirrhosis and chronic active hepatitis.,,TargetActionsOrganismAPeroxisome proliferator-activated receptor alphaagonistHumansUNuclear receptor subfamily group I member partial agonistHumansUMatrix metalloproteinase-inhibitorHumans",[],"['Acids, Acyclic', 'Agents Causing Muscle Toxicity', 'Benzene Derivatives', 'Benzophenones', 'BSEP/ABCB11 Substrates', 'Butyrates', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Ethers', 'Fatty Acids', 'Fatty Acids, Volatile', 'Fibric Acid Derivatives', 'Fibric Acids', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Isobutyrates', 'Ketones', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'Lipids', 'Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia', 'Noxae', 'P-glycoprotein inhibitors', 'Peroxisome Proliferator Receptor alpha Agonist', 'Peroxisome Proliferator-activated Receptor alpha Agonists', 'Phenols', 'Phenyl Ethers', 'Toxic Actions', 'UGT1A9 Substrates']" +DB01418,Acenocoumarol,"Acenocoumarolis an anticoagulant drug used in the prevention of thromboembolic diseases in infarction and transient ischemic attacks, as well as management of deep vein thrombosis and myocardial infarction.",['Q9BQB6'],"Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol.",CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O,"Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.TargetActionsOrganismAVitamin K epoxide reductase complex subunit inhibitorHumans",[],"['4-Hydroxycoumarins', 'Anticoagulants', 'Benzopyrans', 'Blood and Blood Forming Organs', 'Coumarins', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Pyrans', 'Vitamin K Antagonists']" +DB00248,Cabergoline,Cabergolineis a dopamine receptor agonist used for the treatment of hyperprolactinemic conditions due to various causes.,"['P14416', 'P41595', 'P35462', 'P28223', 'P18089', 'P28221', 'P21917', 'P08913', 'P08908', 'P18825', 'P21918', 'P21728', 'P28222', 'P28335', 'P34969', 'P35348', 'P35368', 'P25100', 'P08588', 'P07550', 'P21728', 'P21918']","Cabergoline stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1and D5subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3and D4subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2and D3receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits: agonist activity (in order of decreasing binding affinities) on 5-hydroxytryptamine (5-HT)2B, 5-HT2A, 5-HT1D, dopamine D4, 5-HT1A, dopamine D1, 5-HT1Band 5-HT2Creceptors and antagonist activity on α2B, α2A, and α2Creceptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2Aagonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion.",[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@H](CN2CC=C)C(=O)N(CCCN(C)C)C(=O)NCC,"The dopamine Dreceptor is a -transmembrane G-protein coupled receptor associated with Giproteins. In lactotrophs, stimulation of dopamine Dcauses inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP-dependent release of Ca+from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p/p MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine Dreceptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D receptors. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D, α,- and α- adrenergic, and -HT- and -HT-serotonin receptors.TargetActionsOrganismADopamine D receptoragonistHumansU-hydroxytryptamine receptor BagonistHumansUDopamine D receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansUAlpha-B adrenergic receptorantagonistHumansU-hydroxytryptamine receptor DagonistHumansUDopamine D receptoragonistHumansUAlpha-A adrenergic receptorantagonistHumansU-hydroxytryptamine receptor AagonistHumansUAlpha-C adrenergic receptorantagonistHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor CagonistHumansU-hydroxytryptamine receptor antagonistHumansUAlpha-A adrenergic receptorbinderHumansUAlpha-B adrenergic receptorbinderHumansUAlpha-D adrenergic receptorbinderHumansUBeta- adrenergic receptorbinderHumansUBeta- adrenergic receptorbinderHumansUD() dopamine receptoragonistHumans",['Inhibition of physiological lactation'],"['Agents that produce hypertension', 'Alkaloids', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Antineoplastic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Ergot-derivative Dopamine Receptor Agonists', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Prolactine Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists']" +DB00579,Mazindol,Mazindolis a sympathomimetic used to treat obesity in combination with lifestyle modifications.,"['P23975', 'Q01959', 'P31645', 'Q05940']","Mazindol is a sympathomimetic amine that stimulates the central nervous system (nerves and brain), leading to increased your heart rate and blood pressure, and decreased appetite. Since the appetite-suppressing effect of the drug tends to decrease after few weeks of treatment, sympathomimetic appetite suppressants are typically used short-term weight-loss program.",OC1(N2CCN=C2C2=CC=CC=C12)C1=CC=C(Cl)C=C1,"Unlike other sympathomimetic appetite suppressants such as phentermine, mazindol is thought to inhibit the reuptake of norepinephrine rather than to cause its release.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent dopamine transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumansUSynaptic vesicular amine transporterNot AvailableHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Alimentary Tract and Metabolism', 'Anorexigenic Agents & Respiratory and Cerebral Stimulants, Miscellaneous', 'Anorexigenic Agents & Respiratory and CNS Stimulants', 'Antidepressive Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Central Nervous System Stimulants', 'Centrally Acting Antiobesity Products', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Isoindoles', 'Membrane Transport Modulators', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB00708,Sufentanil,"Sufentanilis an opioid used to induce and maintain anesthesia, to act as an analgesic in labor and delivery, and to treat severe, acute pain.","['P35372', 'P41143', 'P41145']","Effect on the Central Nervous System (CNS)In clinical settings, sufentanil exerts its principal pharmacologic effects on the central nervous system. Its primary therapeutic actions are analgesia and sedation. Sufentanil may increase pain tolerance and decrease the perception of pain. This drug depresses the respiratory centers, depresses the cough reflex, and constricts the pupils12,9. When used in balanced general anesthesia, sufentanil has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, sufentanil is approximately 5 to 7 times as potent as fentanylLabel. High doses of intravenous sufentanil have been shown to cause muscle rigidity, likely as a result of an effect on the substantia nigra and the striate nucleus in the brain. Sleep-inducing (hypnotic) activity can be demonstrated by EEG alterationsLabel.Effects on the Respiratory SystemSufentanil may cause respiratory depressionLabel.Effects on the Cardiovascular SystemSufentanil causes peripheral vasodilation which may result in orthostatic hypotension or syncope. Bradycardia may also occur12. Clinical signs or symptoms of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotensionLabel.Effects on the Gastrointestinal TractSufentanil causes a reduction in motility associated with an increase in smooth muscle tone in both the antrum of the stomach and duodenum. Digestion of food in the small intestine may be delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased and lead to spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of the sphincter of Oddi, as well as temporary elevations in serum amylaseLabel.",CCC(=O)N(C1=CC=CC=C1)C1(COC)CCN(CCC2=CC=CS2)CC1,"Sufentanil is a synthetic, potent opioid with highly selective binding to μ-opioid receptors. These receptors are widely distributed in the human brain, spinal cord, and other tissues,.In general, opioids decrease cAMP (affecting neural signaling pathways), decrease neurotransmitter release, and cause membrane hyperpolarization, all of which contribute to the relief of painful symptoms.Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic neural transmission via G-proteins that activate effector proteins. Binding of the opiate receptor leads to the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP, located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. The release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is then inhibited.Opioids close N-type voltage-operated calcium channels (OP-receptor agonist), also preventing neurotransmitter release.Sufentanil and other opioids open calcium-dependent inwardly rectifying potassium channels, resulting in hyperpolarization and reduced neuronal excitability,.TargetActionsOrganismAMu-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansUKappa-type opioid receptorNot AvailableHumans","['General Anesthesia', 'Induction and Maintenance of General Anesthesia', 'Lumbar epidural anesthesia therapy', 'Short opioid analgesia requirement']","['Adjuvants, Anesthesia', 'Agents that produce hypertension', 'Analgesics', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Bradycardia-Causing Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fentanyl and fentanyl analogues', 'High-risk opioids', 'Hypotensive Agents', 'Narcotics', 'Nervous System', 'Neuraxial Anesthetics', 'Opiate Agonists', 'Opioid Agonist', 'Opioid Anesthetics', 'Opioids', 'Opioids, Anilidopiperidine', 'Peripheral Nervous System Agents', 'Phenylpiperidine opioids', 'Piperidines', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00296,Ropivacaine,Ropivacaineis an amide-type local anesthetic used for local or regional anesthesia during surgery and for short-term management of acute pain.,['Q9Y5Y9'],"In contrast to most other local anesthetics, the presence ofepinephrinedoes not affect the time of onset, duration of action, or the systemic absorption of ropivacaine.2",CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C,"Local anesthetics like ropivacaine block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Specifically, they block the sodium channel and decrease chances of depolarization and consequent action potentials. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",['Surgical anesthesia therapy'],"['Amides', 'Amines', 'Anesthetics', 'Anesthetics, Local', 'Anilides', 'Aniline Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Local Anesthesia', 'Local Anesthetics (Amide)', 'Methemoglobinemia Associated Agents', 'Nervous System', 'Neuraxial Anesthetics', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB01120,Gliclazide,Gliclazideis a sulfonylurea used to treat hyperglycemia in patients with type 2 diabetes mellitus.,"['Q09428', 'P15692']","Based on the pharmacological properties, gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.",[H][C@@]12CCC[C@]1([H])CN(C2)NC(=O)NS(=O)(=O)C1=CC=C(C)C=C1,"Gliclazide binds to the β cell sulfonyl urea receptor (SUR). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.TargetActionsOrganismAATP-binding cassette sub-family C member binderHumansUVascular endothelial growth factor Aother/unknownHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'Oral Hypoglycemics', 'Sulfonamides', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB00420,Promazine,Promazineis a phenothiazine used to manage schizophrenia.,"['P14416', 'P28223', 'P28335', 'P35348', 'P11229', 'P35367']","Promazine belongs to a group of medications known as the phenothiazine antipsychotics. It acts by blocking a variety of receptors in the brain, particularly dopamine receptors. Dopamine is involved in transmitting signals between brain cells. When there is an excess amount of dopamine in the brain it causes over-stimulation of dopamine receptors. These receptors normally act to modify behaviour and over-stimulation may result in psychotic illness. Promazine hydrochloride blocks these receptors and stops them becoming over-stimulated, thereby helping to control psychotic illness. Promazine has weak extrapyramidal and autonomic side effects which lead to its use in the elderly, for restless or psychotic patients. Its anti-psychotic effect is also weaker and it is not useful in general psychiatry.",CN(C)CCCN1C2=CC=CC=C2SC2=CC=CC=C12,"Promazine is an antagonist at types , , and dopamine receptors, -HT receptor types A and C, muscarinic receptors through , alpha()-receptors, and histamine H-receptors. Promazine's antipsychotic effect is due to antagonism at dopamine and serotonin type receptors, with greater activity at serotonin -HT receptors than at dopamine type- receptors. This may explain the lack of extrapyramidal effects. Promazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H-receptors, and alpha()-receptors also occurs with promazine.TargetActionsOrganismADopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUHistamine H receptorantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amino Acids', 'Amino Acids, Branched-Chain', 'Amino Acids, Peptides, and Proteins', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antiemetics', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Moderate Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenothiazines', 'Phenothiazines With Aliphatic Side-Chain', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB01239,Chlorprothixene,Chlorprothixeneis a thioxanthene antipsychotic.,"['P14416', 'P21728', 'P35462', 'P28223', 'P35367', 'P08908', 'P28222', 'P28221', 'P28566', 'P30939', 'P28223', 'P41595', 'P28335', 'P46098', 'O95264', 'Q8WXA8', 'Q70Z44', 'A5X5Y0', 'Q13639', 'P50406', 'P34969', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Chlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). Chlorprothixene has not thoroughly demonstrated an antidepressant or analgesic effect but it has demonstrated antiemetic effects. It is used in the treatment of nervous, mental, and emotional conditions. Improvement in such conditions is thought to result from the effect of the medicine on nerve pathways in specific areas of the brain. Chlorprothixene has a similar side effect profile to chlorpromazine, though allergic side effects and liver damage are less frequent.",CN(C)CC\C=C1\C2=CC=CC=C2SC2=CC=C(Cl)C=C12,"Chlorprothixene blocks postsynaptic mesolimbic dopaminergic D and D receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansAHistamine H receptorantagonistHumansASerotonin ReceptorsinhibitorHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumansNMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thioxanthene Derivatives', 'Thioxanthenes', 'Tranquilizing Agents', 'Xanthenes']" +DB00718,Adefovir dipivoxil,Adefovir dipivoxilis a nucleotide analog used to treat chronic hepatitis B.,['P24024'],Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity.,CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C(N)N=CN=C12)OCOC(=O)C(C)(C)C,"Adefovir dipivoxil is a prodrug of adefovir. Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. The inhibition constant (Ki) for adefovir diphosphate for HBV DNA polymerase was . μM. Adefovir diphosphate is a weak inhibitor of human DNA polymerases α and γ with Ki values of . μM and .μM, respectively.TargetActionsOrganismADNA polymerase/reverse transcriptaseotherHBV-D",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'Nephrotoxic agents', 'Nucleic Acid Synthesis Inhibitors', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleosides and Nucleotides', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'Organophosphorus Compounds', 'Purines', 'Reverse Transcriptase Inhibitors']" +DB01116,Trimethaphan,"A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.",['Q9GZZ6'],"Trimethaphan is indicated for production of controlled hypotension during surgery to reduce bleeding into the surgical field and also for rapid reduction of blood pressure in the treatment of hypertensive emergencies, especially in patients with acute dissecting aneurysm, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension.",O=C1N(CC2=CC=CC=C2)C2C[S+]3CCCC3C2N1CC1=CC=CC=C1,"Trimethaphan is a ganglionic blocking agent prevents stimulation of postsynaptic receptors by competing with acetylcholine for these receptor sites. Additional effects may include direct peripheral vasodilation and release of histamine. Trimethaphan's hypotensive effect is due to reduction in sympathetic tone and vasodilation, and is primarily postural.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumans",[],"['Adjuvants, Anesthesia', 'Antiadrenergic Agents, Ganglion-Blocking', 'Anticholinergic Agents', 'Antihypertensive Agents', 'Autonomic Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Cholinergic Agents', 'Cholinesterase substrates', 'Ganglion Blockers', 'Imidazoles', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Peripheral Nervous System Agents', 'Sulfonium Derivatives', 'Vasodilating Agents']" +DB01595,Nitrazepam,"Nitrazepamis a long-acting benzodiazepine with intermediate onset commonly used to treat panic disorders, severe anxiety, insomnia, and seizures.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928', 'P35498']","Nitrazepam is a type of benzodiazepine drug. It is a powerful hypnotic drug which possesses strong sedative, anxiolytic, amnestic, anticonvulsant, and skeletal muscle relaxant properties. Nitrazepam shortens the time required to fall asleep and lengthens the duration of sleep. It is also useful for the management of myoclonic seizures.",[O-][N+](=O)C1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2)C=C1,"Nitrazepam belongs to a group of medicines called benzodiazepines. This drug affects central benzodiazepine receptors, which are associated with inhibitory GABA (gamma amino butyric acid)receptors, leading to enhanced GABA binding activity. GABA is a major neurotransmitter in the brain, which causes somnolence, relaxation of muscles, a decrease in anxiety and general central nervous system depression. Nitrazepam has anticonvulsant properties that may be attributed to its ability to bind to voltage-dependent sodium channels. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumansUSodium channel protein type subunit alphaother/unknownHumans",[],"['Anti-Anxiety Agents', 'Anticonvulsants', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00807,Proparacaine,Proparacaineis a topical anesthetic used for ophthalmic practice.,['Q9Y5Y9'],"Proparacaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action. More specifically, proparacaine appears to bind or antagonize the function of voltage gated sodium channels.",CCCOC1=C(N)C=C(C=C1)C(=O)OCCN(CC)CC,"The exact mechanism whereby proparacaine and other local anesthetics influence the permeability of the cell membrane is unknown; however, several studies indicate that local anesthetics may limit sodium ion permeability through the lipid layer of the nerve cell membrane. Proparacaine may alter epithelial sodium channels through interaction with channel protein residues. This limitation prevents the fundamental change necessary for the generation of the action potential.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",['Local Anaesthesia therapy'],"['Acids, Carbocyclic', 'Aminobenzoates', 'Anesthetics', 'Anesthetics, Local', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Ethers', 'Hydroxy Acids', 'Hydroxybenzoate Ethers', 'Hydroxybenzoates', 'Isomerism', 'Local Anesthesia', 'Ophthalmologicals', 'para-Aminobenzoates', 'Peripheral Nervous System Agents', 'Phenols', 'Phenyl Ethers', 'Sensory Organs', 'Sensory System Agents']" +DB00899,Remifentanil,Remifentanilis an opioid analgesic used in anesthesia.,"['P35372', 'P41143', 'P41145']",Remifentanil is an opioid agonist with rapid onset and peak effect and ultra-short duration of action. The opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone. The analgesic effects of remifentanil are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other opioids. Remifentanil in humans has a rapid blood-brain equilibration half-time of 1 ± 1 minutes (mean ± SD) and a rapid onset of action.,CCC(=O)N(C1=CC=CC=C1)C1(CCN(CCC(=O)OC)CC1)C(=O)OC,"Remifentanil is a µ-opioid agonist with rapid onset and peak effect, and short duration of action. The µ-opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone.TargetActionsOrganismAMu-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumans","['Immediate postoperative analgesia therapy', 'Induction and Maintenance of General Anesthesia', 'Monitored anesthesia care sedation']","['Acids, Acyclic', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Analgesics', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Bradycardia-Causing Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Fentanyl and fentanyl analogues', 'High-risk opioids', 'Hypnotics and Sedatives', 'Hypotensive Agents', 'Narcotics', 'Nervous System', 'Opiate Agonists', 'Opioid Agonist', 'Opioid Anesthetics', 'Opioids', 'Opioids, Anilidopiperidine', 'Peripheral Nervous System Agents', 'Phenylpiperidine opioids', 'Piperidines', 'Propionates', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00633,Dexmedetomidine,Dexmedetomidineis an alpha-2 agonist used for sedation during various procedures.,['P08913'],"Dexmedetomidine activates 2-adrenoceptors, and causes the decrease of sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; it reduces anesthetic and opioid requirements; and causes sedation and analgesia.",C[C@H](C1=CNC=N1)C1=C(C)C(C)=CC=C1,"Dexmedetomidine is a specific and selective alpha- adrenoceptor agonist. By binding to the presynaptic alpha- adrenoceptors, it inhibits the release if norepinephrine, therefore, terminate the propagation of pain signals. Activation of the postsynaptic alpha- adrenoceptors inhibits the sympathetic activity decreases blood pressure and heart rate.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anesthetics', 'Anesthetics, General', 'Bradycardia-Causing Agents', 'Central alpha-2 Adrenergic Agonist', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypnotics and Sedatives', 'Hypotensive Agents', 'Imidazoles', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Nervous System', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Psycholeptics', 'Sensory System Agents']" +DB00268,Ropinirole,Ropiniroleis a non-ergoline dopamine agonist used to treat the symptoms of Parkinson's disease and Restless Legs Syndrome.,"['P35462', 'P14416', 'P21917', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Effects on Parkinson's and restless leg syndromeThis drug promotes the relief or improvement of symptoms of Parkinson's or restless leg syndrome by stimulatory actions on dopamine receptors, which regulate movement.Effects on blood pressureClinical experience with dopamine agonists, including ropinirole, suggests an association with impaired abilities in regulating blood pressure with resulting orthostatic hypotension, especially with patients undergoing dose escalation. In some patients in clinical studies, blood pressure changes were associated with orthostatic symptoms, bradycardia, and, in one case in a healthy volunteer, transient sinus arrest accompanied by syncopeLabel. The mechanism of orthostatic hypotension caused by ropinirole is assumed to be due to a D2-mediated blunting of noradrenergic response to a standing position, followed by a decrease in peripheral vascular resistance. Nausea is also a frequent symptom which accompanies orthostatic signs and symptomsLabel.Effects on prolactinAt oral doses as low as 0.2 mg, ropinirole suppressed serum prolactin concentrations in healthy male volunteers. +Ropinirole had no dose-related effect on ECG wave form and rhythm in young, healthy, male volunteers in the range of 0.01 to 2.5 mgLabel.Effects on QT intervalRopinirole had no dose- or exposure-related effect on average QT intervals in healthy male and female volunteers at doses up to 4 mg/day. The effect of ropinirole on QTc intervals at higher exposures reached either due to drug interactions, hepatic dysfunction, or at higher doses has not been adequately evaluatedLabel.",CCCN(CCC)CCC1=C2CC(=O)NC2=CC=C1,"Ropinirole is a non-ergoline dopamine agonist. Ropinirole has the highest affinity at the D receptors, which are concentrated in the limbic areas of the brain and may be responsible for some of the neuropsychiatric effects. The exact mechanism of action of ropinirole as a treatment for Parkinson’s disease is unknown, however, it is believed to be related to its ability to selectively stimulate dopamine D receptors within the caudate-putamen system in the brain. This system affects body movement. Negligible affinity is seen for ropinirole at α adrenoreceptors in the periphery and HT- receptor. Ropinirole has no affinity at the D-like receptors, benzodiazepine or GABA receptors.The precise mechanism of action of ropinirole as a treatment for Restless Legs Syndrome is unknown, however, it is believed to be related to its ability to stimulate dopamine receptorsLabel.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansUDopamine D receptoragonistHumansUAlpha adrenergic receptorantagonistHumans",[],"['Anti-Dyskinesia Agents', 'Anti-Parkinson Agents (Dopamine Agonist)', 'Anti-Parkinson Drugs', 'Central Nervous System Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Nervous System', 'Neurotransmitter Agents', 'Nonergot-derivative Dopamine Receptor Agonists']" +DB01628,Etoricoxib,Etoricoxibis a selective COX-2 inhibitor used to relieve moderate post-surgical dental pain as a short-term treatment and inflammatory and painful symptoms of various forms of arthritis.,['P35354'],Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1).,CC1=NC=C(C=C1)C1=C(C=C(Cl)C=N1)C1=CC=C(C=C1)S(C)(=O)=O,"Like any other COX- selective inhibitor Etoricoxib selectively inhibits isoform of cyclo-oxigenase enzyme (COX-), preventing production of prostaglandins (PGs) from arachidonic acid.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Peripheral Nervous System Agents', 'Pyridines', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Sulfones', 'Sulfur Compounds']" +DB09212,Loxoprofen,Loxoprofenis an NSAID used to treat pain and inflammation in musculoskeletal conditions.,"['P35354', 'P23219']","Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid.7,8",CC(C(O)=O)C1=CC=C(CC2CCCC2=O)C=C1,"Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase.Cyclooxygenase (COX) is present in forms, COX- and COX-, with each serving different functions. COX- is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation.COX- is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain.Loxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc).TargetActionsOrganismAProstaglandin G/H synthase antagonistHumansAProstaglandin G/H synthase antagonistHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain', 'UGT2B7 substrates']" +DB01384,Paramethasone,"A glucocorticoid with the general properties of corticosteroids. It has been used by mouth in the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than hydrocortisone with supplementary fludrocortisone. (From Martindale, The Extra Pharmacopoeia, 30th ed, p737)",['P04150'],"Paramethasone is a glucocorticoid with the general properties of corticosteroids. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.",[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C,"Glucocorticoids such as paramethasone can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Paramethasone reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Prednisolone is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL (interleukin ) expression.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB12965,Silver,"Silver (Ag) is a chemical element that belongs in the family of transition metals in the periodic table. It has a high electrical conductivity, thermal conductivity, and reflectivity. Silver exists as a pure elemental form, alloy with other metals, and mineral. Having critical roles in various applications inducing chemical and industrial fields, silver compounds have also been used in the field of medicine for centuries due to their broad-spectrum biological actions. Silver nanoparticles especially have been widely used in industrial, household, and healthcare-related products due to their potent antimicrobial activity.Silver nitrateandSilver sulfadiazinehave been used as topical antibacterial agents for the treatment of skin infections, whileSilver sulfadiazinehas also been valued for topical burn treatment3. Silver and its compounds have been used in trials studying the management of dental caries since the 1800s, and they may be found in dental pastes as an active ingredients. However, some drawbacks of dental use of silver compounds include tooth discolouration and pulp irritation3.","['Q14872', 'P0DM35', 'P04731', 'P07438', 'P04732', 'P04733', 'P13640', 'P80294', 'Q93083', 'Q8N339', 'P80297', 'P02795', 'P25713', 'P47944', 'A1L3X4', 'Q9Y4I5', 'P00450', 'P02768', 'P01023']","Silver exhibits a broad-spectrum antimicrobial activity. Silver ions were shown to mediate an effective antibacterial action againstStreptococcus mutans, one of major bacteria present in the human oral cavity and one of etiological microorganism of dental caries3. A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria2. Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positiveS. aureusand Gram-negativeE. coliby inhibiting the growth4.In experimental dinitrochlorobenzene-induced inflammatory models in porcine or murine skin, topical application of silver nitrate and nanocrystalline silver were shown to exert anti-inflammatory effects associated with lymphocyte apoptosis, decreased expression of pro-inflammatory cytokines, and reduced gelatinase activity1. In a rat model of ulcerative colitis, orally or intracolonically administered nanocrystalline silver were shown to suppress matrix metalloproteinase (MMP-9), tumour necrosis factor (TNF), and interleukin-β (IL-β) and IL-121.",[Ag],"The majority of released silver ions precipitate with chloride or phosphate anions or bind to albumins, macroglobulins, or tissue debris. While bound silver ions do not exert antibacterial actions, they may potentially play a role in silver toxicity in case of chronic exposure. Silver ions mediate antibacterial effects via disrupting the bacterial, fungal, and protozoal cell membranes; they bind to disulphide in membrane proteins, readily allowing penetration through the membranes and intracellular absorption via pinocytosis. They may also bind to negatively-charged peptidoglycans in the cell wall via electrostatic interactions, leading to disruption of membrane transport function and loss of structural integrity. Silver ions also bind to and oxidize sulphydryl groups (SH) in bacterial cytoplasmic enzymes to aberrate their function in metabolic processes. Silver nanoparticles may cause an increase in reactive oxygen species (ROS) inside the microbial cells leading to metal-induced oxidative stress and cell damage. They also modulate cellular signal system via inhibition of phosphorylation of essential bacterial proteins to eventually cause cell death. It is also reported that silver ions also attach to guanine in bacterial DNA, which inhibits DNA replication. While it is not fully understood, the mode of action of silver compounds in preventing and arresting dental caries is thought to involve inhibition of the demineralization process in addition to cytoplasmic and membrane function perturbation mentioned above. Silver compounds may directly interact with hydroxyapatite, a major tooth component.TargetActionsOrganismUMetallothioneinbinderHumansUCeruloplasminbinderHumansUSerum albuminbinderHumansUAlpha--macroglobulinbinderHumans",[],"['Antiseptics and Disinfectants', 'Dermatologicals', 'Elements', 'Metals', 'Metals, Heavy', 'Silver Compounds', 'Transition Elements']" +DB00592,Piperazine,Piperazineis a medication used to treat roundworm and pinworm.,['P28472'],"Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.",C1CNCCN1,"Piperazine is a GABA receptor agonist. Piperzine binds directly and selectively to muscle membrane GABA receptors, presumably causing hyperpolarization of nerve endings, resulting in flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit beta-agonistHumans",[],"['Anthelmintics', 'Anti-Infective Agents', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Hyperglycemia-Associated Agents', 'Piperazine and Derivatives', 'Piperazines']" +DB00411,Carbachol,"Carbacholis a direct acting miotic agent administered ophthalmically to decrease intraocular pressure after cataract surgery, and to induce miosis during surgery.","['P11229', 'P08172', 'Q15822', 'P20309', 'P08173']","Carbamoylcholine is a parasympathomimetic that acts as an agonist of muscarinic and nicotinic receptors.3,9It is more resistant to hydrolysis by acetylcholinesterase than other choline esters leading to a longer duration of action, with significant effects 24 hours after administration.5Data regarding the therapeutic index of carbamoylcholine is not readily available.9Patients should be counselled regarding the risk of administering the drug to patients with acute cardiac failure, bronchial asthma, peptic ulcer, hyperthyroidism, gastrointestinal spasm, urinary tract obstruction, or Parkinson's disease.9",C[N+](C)(C)CCOC(N)=O,"Carbamoylcholine is a parasympathomimetic that acts as an agonist of muscarinic and nicotinic receptors.,Intraocular administration leads to miosis and decreases intraocular pressure via increased aqueous humour outflow.,TargetActionsOrganismAMuscarinic acetylcholine receptor MagonistHumansAMuscarinic acetylcholine receptor MagonistHumansANeuronal acetylcholine receptor subunit alpha-agonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumans",[],"['Alcohols', 'Amines', 'Amino Alcohols', 'Ammonium Compounds', 'Analgesics', 'Analgesics, Non-Narcotic', 'Antiglaucoma Preparations and Miotics', 'Autonomic Agents', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Choline Esters', 'Cholinergic Agents', 'Cholinergic Agonists', 'Cholinergic Receptor Agonist', 'Compounds used in a research, industrial, or household setting', 'Ethanolamines', 'Miotics', 'Nervous System', 'Neurotransmitter Agents', 'Nitrogen Compounds', 'Onium Compounds', 'Ophthalmologicals', 'Parasympathomemetic (Cholinergic) Agents', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Protective Agents', 'Quaternary Ammonium Compounds', 'Sensory Organs', 'Sensory System Agents', 'Trimethyl Ammonium Compounds']" +DB01218,Halofantrine,Halofantrineis an antimalarial used for the treatment of severe malaria.,"['Q12809', 'P46925']",Halofantrine is a synthetic antimalarial which acts as a blood schizonticide. It is effective against multi drug resistant (including mefloquine resistant)P. falciparummalaria.,CCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C2C=C(Cl)C=C(Cl)C2=C1)C(F)(F)F,"The mechanism of action of Halofantrine may be similar to that of chloroquine, quinine, and mefloquine; by forming toxic complexes with ferritoporphyrin IX that damage the membrane of the parasite.TargetActionsOrganismAFe(II)-protoporphyrin IXantagonistPlasmodium falciparumAPotassium voltage-gated channel subfamily H member inhibitorHumansUPlasmepsin-inhibitorPlasmodium falciparum",[],"['Agents that reduce seizure threshold', 'Anti-Infective Agents', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Highest Risk QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB01002,Levobupivacaine,Levobupivacaineis a drug used for nerve block and anesthesia.,['Q9Y5Y9'],"Levobupivacaine, a local anesthetic agent, is indicated for the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.",CCCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C,"Local anesthetics such as Levobupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Specifically, the drug binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans","['Local Anaesthesia therapy', 'Lumbar epidural anesthesia therapy']","['Amides', 'Amines', 'Anesthetics', 'Anesthetics, Local', 'Anilides', 'Aniline Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Nervous System', 'Neuraxial Anesthetics', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB00379,Mexiletine,Mexiletineis a class 1B antiarrhythmic agent used in the treatment of documented ventricular arrhythmias that warrant treatment.,"['Q14524', 'P35869']","Mexiletine is a local anesthetic, antiarrhythmic agent (Class Ib), structurally similar to lidocaine, but orally active. Mexiletine has fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. It shortens the action potential duration, reduces refractoriness, and decreases Vmax in partially depolarized cells with fast response action potentials. Mexiletine either does not change the action potential duration, or decreases the action potential duration.",CC(N)COC1=C(C)C=CC=C1C,"Mexiletine, like lidocaine, inhibits the inward sodium current required for the initiation and conduction of impulses, thus reducing the rate of rise of the action potential, Phase . It achieves this reduced sodium current by inhibiting sodium channels. Mexiletine decreases the effective refractory period (ERP) in Purkinje fibers in the heart. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), which results in an increase in the ERP/APD ratio. It does not significantly affect resting membrane potential or sinus node automaticity, left ventricular function, systolic arterial blood pressure, atrioventricular (AV) conduction velocity, or QRS or QT intervalsTargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUAryl hydrocarbon receptoragonistHumans",[],"['Amines', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ib', 'Benzene Derivatives', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Membrane Transport Modulators', 'Phenols', 'Phenyl Ethers', 'Propylamines', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB04957,Azimilide,"Azimilide is an investigational class III anti-arrhythmic drug that blocks fast and slow components of the delayed rectifier cardiac potassium channels. It is not approved for use in any country, but is currently in clinical trials in the United States.","['P15382', 'P51787', 'Q12809']","Azimilide is a new class III anti-arrhythmic agent. It is distinguished by a relative lack of reverse use-dependence, excellent oral absorption, no need for dose titration, an option for out-patient initiation, no need for adjustment associated with renal or liver failure and a lack of interaction with warfarin or digoxin. It carries some risk of torsade de pointes and rarely, neutropoenia.",CN1CCN(CCCCN2C(=O)CN(N=CC3=CC=C(O3)C3=CC=C(Cl)C=C3)C2=O)CC1,"The mechanism of action of azimilide is to block both the slowly conducting (I(Ks)) and rapidly conducting (I(Kr)) rectifier potassium currents in cardiac cells. This differs from other class III agents that block I(Kr) exclusively or in combination with sodium, calcium, or transient outward (I(to)) potassium current channels. It also has blocking effects on sodium (I(Na)) and calcium currents (I(CaL)). Its effects on reentrant circuits in infarct border zones causing ventricular tachyarrhythmias are unknown.TargetActionsOrganismUPotassium voltage-gated channel subfamily E member Not AvailableHumansUPotassium voltage-gated channel subfamily KQT member Not AvailableHumansUPotassium voltage-gated channel subfamily H member Not AvailableHumans",[],"['Antiarrhythmic agents', 'Antiarrhythmics, Class III', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Imidazoles', 'Imidazolidines', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00933,Mesoridazine,"Mesoridazineis a phenothiazine antipsychotic used to treat schizophrenia, organic brain disorders, alcoholism, and psychoneuroses.","['P14416', 'P28223']","Mesoridazine, the besylate salt of a metabolite of thioridazine, is a phenothiazine tranquilizer. Pharmacological studies in laboratory animals have established that mesoridazine has a spectrum of pharmacodynamic actions typical of a major tranquilizer. In common with other tranquilizers it inhibits spontaneous motor activity in mice, prolongs thiopental and hexobarbital sleeping time in mice and produces spindles and block of arousal reaction in the EEG of rabbits. It is effective in blocking spinal reflexes in the cut and antagonizes d-amphetamine excitation and toxicity in grouped mice. It shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo. Intravenously administered, it lowers the blood pressure of anesthetized dogs. It has a weak antiacetylcholine effect in vitro.",CN1CCCCC1CCN1C2=C(SC3=C1C=C(C=C3)S(C)=O)C=CC=C2,"Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.TargetActionsOrganismADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Phenothiazines', 'Phenothiazines With Piperidine Structure', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB00680,Moricizine,Moricizineis an antiarrhythmic used to treat arrhythmias.,['Q14524'],"Moricizine is used to treat irregular heartbeats (arrhythmias) and to maintain a normal heart rate. It acts on the heart muscle to improve the heart's rhythm. Moricizine has potent local anesthetic activity and membrane stabilizing effect. Decreases excitability, conduction velocity, and automaticity as a result of slowed atrioventricular (AV) nodal and His-Purkinje conduction. Decreases the action potential duration (APD) in Purkinje fibers; also decreases the effective refractory period (ERP) but to a lesser extent than the APD, so the ERP/APD ratio is increased. Decreases the maxiumum rate of Phase 0 depolarization (V max ), but does not affect action potential amplitude or maximum diastolic potential. Does not affect atrial, AV nodal, or left ventricular refractory periods and has minimal effect on ventricular repolarization (evidenced by the overall decrease in JT interval). Has no effect on sinoatrial (SA) nodal or intra-atrial conduction and only minimal effect on sinus cycle length and sinus node recovery time. In the Vaughan Williams classification of antiarrhythmics, moricizine is considered to be a class I agent. It has properties of class IA, IB, and IC agents but does not clearly belong to any of the three subclasses. It has less effect on the slope of phase 0 and a greater effect on action potential duration and effective refractory period than class IC agents.",CCOC(=O)NC1=CC2=C(SC3=CC=CC=C3N2C(=O)CCN2CCOCC2)C=C1,Moricizine works by inhibiting the rapid inward sodium current across myocardial cell membranes.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans,[],"['Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ic', 'Antipsychotic Agents', 'Cardiac Therapy', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Membrane Transport Modulators', 'Morpholines', 'Neurotoxic agents', 'Oxazines', 'Phenothiazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Sulfur Compounds', 'Voltage-Gated Sodium Channel Blockers']" +DB00204,Dofetilide,Dofetilideis a class III antiarrhythmic drug used for the maintenance of normal sinus rhythm and cardioversion in cases of atrial fibrillation and atrial flutter.,"['Q12809', 'O95069', 'Q14500']","Dofetilide is an antiarrhythmic drug with Class III (cardiac action potential duration prolonging) properties and is indicated for the maintenance of normal sinus rhythm. Dofetilide increases the monophasic action potential duration in a predictable, concentration-dependent manner, primarily due to delayed repolarization. At concentrations covering several orders of magnitude, Dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, Dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors.",CN(CCOC1=CC=C(NS(C)(=O)=O)C=C1)CCC1=CC=C(NS(C)(=O)=O)C=C1,"The mechanism of action of Dofetilide is a blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. This inhibition of potassium channels results in a prolongation of action potential duration and the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway).TargetActionsOrganismAPotassium voltage-gated channel subfamily H member inhibitorHumansAPotassium channel subfamily K member inhibitorHumansAATP-sensitive inward rectifier potassium channel inhibitorHumans",[],"['Amides', 'Amines', 'Antiarrhythmic agents', 'Antiarrhythmics, Class III', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Ethylamines', 'Highest Risk QTc-Prolonging Agents', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'OCT2 Substrates', 'OCT2 Substrates with a Narrow Therapeutic Index', 'Potassium Channel Blockers', 'QTc Prolonging Agents', 'Sulfones', 'Sulfur Compounds']" +DB00308,Ibutilide,"Ibutilideis a class III antiarrhythmic agent used to correct atrial fibrillation and atrial flutter, which can be considered as an alternative to cardioversion.","['Q13936', 'Q02641', 'Q12809', 'P54289', 'Q06432', 'O00180', 'Q9Y257', 'Q9H252', 'Q9NS40', 'Q14654']","Ibutilide prolongs the action potential duration and increases both atrial and ventricular refractoriness in vivo, i.e., class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide, at nanomolar concentrations, delays repolarization by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act.",CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1,"Ibutilide is a 'pure' class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca+channel blockers and potent inhibition of the cardiac rapid delayed rectifier K+current, by binding within potassium channel pores. In other words, Ibutilide binds to and alters the activity of hERG potassium channels, delayed inward rectifier potassium (IKr) channels and L-type (dihydropyridine sensitive) calcium channelsTargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CactivatorHumansAVoltage-dependent L-type calcium channel subunit beta-activatorHumansAPotassium voltage-gated channel subfamily H member inhibitorHumansUVoltage-dependent calcium channel subunit alpha-/delta-activatorHumansUVoltage-dependent calcium channel gamma- subunitactivatorHumansUPotassium channel subfamily K member inhibitorHumansUPotassium channel subfamily K member inhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUATP-sensitive inward rectifier potassium channel inhibitorHumans",[],"['Amides', 'Antiarrhythmic agents', 'Antiarrhythmics, Class III', 'Cardiac Therapy', 'Cardiovascular Agents', 'Drugs that are Mainly Renally Excreted', 'Highest Risk QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfones', 'Sulfur Compounds']" +DB00640,Adenosine,Adenosineis a medication used in myocardial perfusion scintigraphy and to treat supraventricular tachycardia.,"['P30542', 'P29274', 'P29275', 'P0DMS8']","Adenosine is indicated as an adjunct to thallium-201 in myocardial perfusion scintigraphy and also indicated for conversion of sinus rhythm of paroxysmal supraventricular tachycardia.12,13Adenosine has a short duration of action as the half life is <10 seconds, and a wide therapeutic window.12,13Patients should be counselled regarding the risk of cardiovascular side effects, bronchoconstriction, seizures, and hypersensitivity.12,13",NC1=C2N=CN([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)C2=NC=N1,"Agonism of adenosine receptors A and A reduces conduction time in the atrioventricular node of the heart.,,Conduction time is decreased by inducing potassium efflux and inhibiting calcium influx through channels in nerve cells, leading to hyperpolarization and and increased threshold for calcium dependent action potentials.Decreased conduction time leads to an antiarrhythmic effect.Inhibition of calcium influx, reduces the activity of adenylate cyclase, relaxing vascular smooth muscle.Relaxed vascular smooth muscle leads to increased blood flow through normal coronary arteries but not stenotic arteries, allowing thallium- to be more readily uptaken in normal coronary arteries.TargetActionsOrganismAAdenosine receptor AagonistHumansAAdenosine receptor AaagonistHumansAAdenosine receptor AbagonistHumansAAdenosine receptor AagonistHumans",[],"['Adenosine, antagonists & inhibitors', 'Agents producing tachycardia', 'Alkenes', 'Analgesics', 'Antiarrhythmic agents', 'Antiarrhythmics, Class V', 'Biological Factors', 'Carbohydrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Cyclohexanes', 'Cyclohexenes', 'Cycloparaffins', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring', 'Hydrocarbons, Acyclic', 'Miscellaneous Cardiac Drugs', 'Miscellaneous Therapeutic Agents', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Peripheral Nervous System Agents', 'Polyenes', 'Purine Nucleosides', 'Purinergic Agents', 'Purinergic Agonists', 'Purinergic P1 Receptor Agonists', 'Purines', 'QTc Prolonging Agents', 'Ribonucleosides', 'Sensory System Agents', 'Terpenes', 'Vasodilating Agents']" +DB00922,Levosimendan,Levosimendanis a calcium sensitizer indicated to treat acutely decompensated severe chronic heart failure.,"['P63316', 'Q14654', 'Q15842', 'Q14432']","Levosimendan is a new Ca2+-sensitizing inotropic agent. Ca2+sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca2+overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Levosimendan has not been approved for use in the U.S. or Canada.",C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1,"Levosimendan appears to increase myofilament calcium sensitivity by binding to cardiac troponin C in a calcium-dependent manner. This stabilizes the calcium-induced conformational change of troponin C, thereby () changing actin-myosin cross-bridge kinetics apparently without increasing the cycling rate of the cross-bridges or myocardial ATP consumption, () increasing the effects of calcium on cardiac myofilaments during systole and () improving contraction at low energy cost (inotropic effect). Calcium concentration and, therefore, sensitization decline during diastole, allowing normal or improved diastolic relaxation. Levosimendan also leads to vasodilation through the opening of ATP-sensitive potassium channels. By these inotropic and vasodilatory actions, levosimendan increases cardiac output without increasing myocardial oxygen demand. Levosimendan also has a selective phosphodiesterase (PDE)-III inhibitory action that may contribute to the inotropic effect of this compound under certain experimental conditions. It has been reported that levosimendan may act preferentially as a Ca+sensitizer at lower concentrations, whereas at higher concentrations its action as a PDE-III inhibitor becomes more prominent in experimental animals and humans.TargetActionsOrganismATroponin C, slow skeletal and cardiac musclespotentiatorHumansAATP-sensitive inward rectifier potassium channel inducerHumansAATP-sensitive inward rectifier potassium channel inducerHumansUcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumans","['Positive cardiac inotropic effect', 'Intravenous inotropic therapy']","['Antiarrhythmic agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Enzyme Inhibitors', 'Hydrazines', 'Hydrazones', 'Hypotensive Agents', 'Moderate Risk QTc-Prolonging Agents', 'Phosphodiesterase 3 Inhibitors', 'Phosphodiesterase Inhibitors', 'Protective Agents', 'Pyridazines', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB01297,Practolol,A beta-adrenergic antagonist that has been used in the emergency treatment of cardiac arrhythmias.,['P08588'],"Practolol is a beta-adrenergic receptor antagonist that has been used in the emergency treatment of cardiac arrhythmias. Beta blockers inhibit normal epinephrine-mediated sympathetic actions, but have minimal effect on resting subjects. That is, they reduce the effect of excitement/physical exertion on heart rate and force of contraction and dilation of blood vessels.",CC(C)NCC(O)COC1=CC=C(NC(C)=O)C=C1,"Like other beta-adrenergic antagonists, practolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, practolol binds at beta()-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure.TargetActionsOrganismABeta- adrenergic receptorantagonistHumans",[],"['Acetanilides', 'Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amides', 'Amines', 'Amino Alcohols', 'Anilides', 'Aniline Compounds', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Beta Blocking Agents, Selective', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Neurotransmitter Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols']" +DB00280,Disopyramide,Disopyramideis a class 1A antiarrhythmic agent used to treat life-threatening ventricular arrhythmias.,"['Q14524', 'P11229', 'P08172', 'P20309', 'Q9NZV8', 'Q9UK17', 'Q12809', 'P19652']","Disopyramide is an anti-arrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. At therapeutic plasma levels, disopyramide shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.",CC(C)N(CCC(C(N)=O)(C1=CC=CC=C1)C1=NC=CC=C1)C(C)C,"Disopyramide is a Type A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase ) in cells with augmented automaticity, decreases the upstroke velocity (phase ) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUPotassium voltage-gated channel subfamily D member inhibitorHumansUPotassium voltage-gated channel subfamily D member inhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUAlpha--acid glycoprotein Not AvailableHumans",[],"['Agents producing tachycardia', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ia', 'Anticholinergic Agents', 'Blood Glucose Lowering Agents', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Highest Risk QTc-Prolonging Agents', 'Hypoglycemia-Associated Agents', 'Membrane Transport Modulators', 'Muscarinic Antagonists', 'Negative Inotrope', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Pyridines', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB00436,Bendroflumethiazide,Bendroflumethiazideis a diuretic used to suppress lactation and to treat hypertension and edema.,"['P55017', 'Q12791', 'P00915', 'P00918', 'P22748']","Bendroflumethiazide, a thiazide diuretic, removes excess water from the body by increasing how often you urinate (pass water) and also widens the blood vessels which helps to reduce blood pressure. It inhibits Na+/Cl-reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.",NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F,"As a diuretic, bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.TargetActionsOrganismASolute carrier family member inhibitorHumansACalcium-activated potassium channel subunit alpha-inducerHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzothiadiazines', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Diuretics', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis', 'Low-Ceiling Diuretics and Potassium-Sparing Agents', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB06637,Dalfampridine,Dalfampridineis a potassium channel blocker used for the improvement of motor function in patients with multiple sclerosis (MS).,"['Q09470', 'P16389', 'P22001', 'P22459', 'P22460', 'P17658', 'Q96RP8', 'Q16322', 'Q14721', 'Q92953', 'P48547', 'Q96PR1', 'Q14003', 'Q9NSA2', 'Q9NZV8', 'Q9UK17']",Dalfampridine is a board-spectrum lipophillic potassium channel blocker and binds favourably to the open state than closed state of the potassium channel in the CNS. Its pharmacological target are the potassium channels exposed in MS patients. Does not prolong the QTc interval.,NC1=CC=NC=C1,"In MS, axons are progressively demyelinated which exposes potassium channels. As a result, there is a leak of potassium ions which results in the repolarization of cells and a decrease in neuronal excitability. The overall impact is the impairment of neuromuscular transmission as it is harder to trigger an action potential. +Dalfampridine inhibits voltage-gated potassium channels in the CNS to maintain the transmembrane potential and prolong action potential. In other words, dalfampridine works to make sure that the current available is high enough to stimulate conduction in demyelinated axons that are exposed in MS patients. Furthermore, it facilitates neuromuscular and synaptic transmission by relieving conduction blocks in demyelinated axons.TargetActionsOrganismAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily A member antagonistHumansAPotassium voltage-gated channel subfamily B member antagonistHumansAPotassium voltage-gated channel subfamily B member antagonistHumansAPotassium voltage-gated channel subfamily C member antagonistHumansAPotassium voltage-gated channel subfamily C member antagonistHumansAPotassium voltage-gated channel subfamily C member antagonistHumansAPotassium voltage-gated channel subfamily D member antagonistHumansAPotassium voltage-gated channel subfamily D member antagonistHumansAPotassium voltage-gated channel subfamily D member antagonistHumans",[],"['Amines', 'Aminopyridines', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'OCT2 Substrates', 'OCT2 Substrates with a Narrow Therapeutic Index', 'Other Miscellaneous Therapeutic Agents', 'Potassium Channel Blockers', 'Pyridines']" +DB04868,Nilotinib,Nilotinibis a kinase inhibitor used for the chronic phase treatment of Chronic Myeloid Leukemia (CML) that is Philadelphia chromosome positive and for the treatment of CML that is resistant to therapy containing imatinib.,"['P00519', 'P10721']","Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML).",CC1=CN(C=N1)C1=CC(NC(=O)C2=CC=C(C)C(NC3=NC=CC(=N3)C3=CN=CC=C3)=C2)=CC(=C1)C(F)(F)F,"Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP-like--PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN for myeloproliferative diseases characterised by these kinase fusions (Stover et al, ; Weisberg et al, ). AMN also inhibits the c-Kit receptor kinase, including the DV-mutated variant of KIT, at pharmacologically achievable concentrations, supporting potential utility in the treatment of mastocytosis, and gastrointestinal stromal tumours (Weisberg et al, ; von Bubnoff et al, ; Gleixner et al, ).TargetActionsOrganismATyrosine-protein kinase ABLinhibitorHumansUMast/stem cell growth factor receptor KitantagonistHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Bcr-Abl Tyrosine Kinase Inhibitors', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Highest Risk QTc-Prolonging Agents', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Tyrosine Kinase Inhibitors', 'UGT1A1 Inhibitors']" +DB00346,Alfuzosin,Alfuzosinis an alpha-1 adrenergic antagonist used in the symptomatic management of benign prostatic hypertrophy (BPH).,"['P35348', 'P35368', 'P25100', 'P35348', 'P35368', 'P25100']","By selectively inhibiting alpha adrenergic receptors in the lower urinary tract, alfuzosin causes smooth muscle relaxation in the bladder neck and prostate, improving urine flow, thereby reducing BPH symptoms.9Additionally, alfuzosin reduces the vasoconstrictor effect of catecholamines (epinephrine and norepinephrine), leading to peripheral vasodilation.11This leads to a risk of postural hypotension/syncope, and prescribing information warns that caution should be exercised in patients who take nitrates, antihypertensives, or have experienced decreased blood pressure after using other medications.9",COC1=CC2=C(C=C1OC)C(N)=NC(=N2)N(C)CCCNC(=O)C1CCCO1,"Alpha()-adrenoreceptors are found in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra; their activation may lead to contraction of smooth muscle and urinary symptoms in patients with BPH.,Alfuzosin selectively binds to and inhibits alpha()-adrenergic receptors in the lower urinary tract.This leads to the relaxation of smooth muscle in both the prostate and bladder neck, resulting in the improvement in urine flow and a reduction of urinary symptoms.TargetActionsOrganismAAlpha- adrenergic receptorsantagonistHumansAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAAlpha-D adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Benign Prostatic Hypertrophy', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Peripheral alpha-1 blockers', 'Potential QTc-Prolonging Agents', 'Prostatic Hyperplasia', 'QTc Prolonging Agents', 'Selective Alfa-1-adrenergic Blocking Agents', 'Urological Agents', 'Urologicals']" +DB01228,Encainide,"Encainideis a voltage-gated sodium channel blocker used for management of atrial or ventricular fibrillation, atrial flutter, and ventricular tachycardia, that is no longer used due to proarrhythmic adverse effects.",['Q14524'],"Used to treat irregular heartbeats, encainide decreases excitability, conduction velocity, and automaticity as a result of slowed atrial, atrioventricular (AV) nodal, His-Purkinje, and intraventricular conduction. It causes a slight but significant prolongation of refractory periods in these tissues. The greatest effect is on the His-Purkinje system. Encainide decreases the rate of rise of the action potential without markedly affecting its duration.",COC1=CC=C(C=C1)C(=O)NC1=CC=CC=C1CCC1CCCCN1C,"Encainide is a sodium channel blocker, binding to voltage gated sodium channels. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",[],"['Amides', 'Amines', 'Anilides', 'Aniline Compounds', 'Antiarrhythmic agents', 'Antiarrhythmics, Class I', 'Antiarrhythmics, Class Ic', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Membrane Transport Modulators', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB01154,Thiamylal,"A barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. (From Martindale, The Extra Pharmacopoeia, 30th ed, p919)","['Q15842', 'Q14654', 'P14867']","Thiamylal, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia.",CCCC(C)C1(CC=C)C(=O)NC(=S)NC1=O,"Thiamylal binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAATP-sensitive inward rectifier potassium channel inhibitorHumansAATP-sensitive inward rectifier potassium channel inhibitorHumansAGamma-aminobutyric acid receptor subunit alpha-agonistHumans",[],"['Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Anticonvulsants', 'Barbiturates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones', 'Thiobarbiturates']" +DB01409,Tiotropium,Tiotropiumis a long-acting bronchodilator used in the management of chronic obstructive pulmonary disease (COPD).,"['P20309', 'P11229', 'P08172', 'P08173', 'P08912']","Tiotropium is a long acting antimuscarinic that causes bronchodilation.1,2,3,4,5The effects of tiotropium last over 24 hours and there is a wide therapeutic index as overdoses are uncommon even at doses well above the recommended maximum.2,3,4,5",[H][C@]12O[C@@]1([H])[C@]1([H])C[C@@]([H])(C[C@@]2([H])[N+]1(C)C)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1,"Tiotropium is an antagonist of muscarinic receptors Mto M.,,,,Inhibition of the Mreceptor in the smooth muscle of the lungs leads to relaxation of smooth muscle and bronchodilation.,,,,TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MNot AvailableHumansUMuscarinic acetylcholine receptor MNot AvailableHumans",[],"['Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents to Treat Airway Disease', 'Alkaloids', 'Anti-Asthmatic Agents', 'Anticholinergic Agents', 'Antimuscarinics Antispasmodics', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Bronchodilator Agents', 'Cholinergic Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Scopolamine Derivatives', 'Tropanes']" +DB01427,Amrinone,Amrinoneis a positive inotropic agent and phosphodiesterase inhibitor used in the management of treatment of congestive heart failure.,"['P27815', 'Q07343', 'Q08493', 'Q08499', 'Q14432', 'Q13370', 'P01375']","Amrinone is a positive inotropic cardiotonic with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.",NC1=CC(=CNC1=O)C1=CC=NC=C1,"Amrinone is a phosphodiesterase inhibitor (PDE), resulting in increased cAMP and cGMP which leads to an increase in the calcium influx like that caused by beta-agonists resulting in increased inotropic effect.TargetActionsOrganismAcAMP-specific ','-cyclic phosphodiesterase (PDE)inhibitorHumansAcAMP-specific ','-cyclic phosphodiesterase inhibitorHumansAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumansUcGMP-inhibited ','-cyclic phosphodiesterase BinhibitorHumansUTumor necrosis factorinhibitorHumans",[],"['Amines', 'Aminopyridines', 'Calcium-Regulating Hormones and Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Membrane Transport Modulators', 'Phosphodiesterase 3 Inhibitors', 'Phosphodiesterase Inhibitors', 'Protective Agents', 'Pyridines', 'Tumor Necrosis Factor Blockers', 'Vasodilating Agents']" +DB00332,Ipratropium,Ipratropiumis an anticholinergic drug used in the control of symptoms related to bronchospasm in chronic obstructive pulmonary disease (COPD).,"['P20309', 'P11229', 'P08172']","Ipratropium is a short-acting agent that inhibits the parasympathetic nervous system at the level of the airway which then produces bronchodilatation. The effect of this agent starts after 1-2 hours and it is known to last only from 4 to 6 hours.3As part of the effect, ipratropium relaxes the bronchial airways which reverse the narrowing that accounts for wheezy breathing, chest tightness, cough and abnormal gas exchange.6In clinical trials where ipratropium was used in the initial management of status asthmaticus, it was demonstrated a clear benefit in pulmonary function in children and adults. However, the continuous use of ipratropium after an acute asthmatic attack is not proven to be significantly advantageous1nor the prophylactic administration of this agent.8",[H][C@]12CC[C@]([H])(C[C@@H](C1)OC(=O)C(CO)C1=CC=CC=C1)[N+]2(C)C(C)C,"Ipratropium acts as an antagonist of the muscarinic acetylcholine receptor.This effect produces the inhibition of the parasympathetic nervous system in the airways and hence, inhibit their function. The function of the parasympathetic system in the airway is to generate bronchial secretions and constriction and hence, the inhibition of this action can lead to bronchodilation and fewer secretions.At the cellular level, the diameter of the airways is controlled by the release of acetylcholine into the muscle cells causing them to contract and producing a narrow airway. Thus administration of ipratropium stops the activity of acetylcholine in the smooth muscle preventing the contraction and producing relaxed airways.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents to Treat Airway Disease', 'Alkaloids', 'Anti-Asthmatic Agents', 'Anticholinergic Agents', 'Antimuscarinics Antispasmodics', 'Atropine Derivatives', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Belladonna Alkaloids', 'Bronchodilator Agents', 'Cholinergic Agents', 'Drugs for Obstructive Airway Diseases', 'Muscarinic Antagonists', 'Nasal Preparations', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Solanaceous Alkaloids', 'Tropanes']" +DB01626,Pargyline,Pargyline is a monoamine oxidase inhibitor with antihypertensive properties.,"['P27338', 'P21397']","Pargyline is a monoamine oxidase B (MAO-B) inhibitor with antihypertensive properties. Patients taking pargyline must avoid concurrent consumption of tyramine-containing foods such as bleu cheese and beer, as this can lead to a hypertensive crisis.",CN(CC#C)CC1=CC=CC=C1,"MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine and norepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Pargyline functions by inhibiting the metabolism of catecholamines and tyramine within presynaptic nerve terminals. Catecholamines cause general physiological changes that prepare the body for physical activity (fight-or-flight response). Some typical effects are increases in heart rate, blood pressure, blood glucose levels, and a general reaction of the sympathetic nervous system.TargetActionsOrganismAAmine oxidase [flavin-containing] BinhibitorHumansUAmine oxidase [flavin-containing] AinhibitorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Amines', 'Antidepressive Agents', 'Antihypertensive Agents', 'Benzene Derivatives', 'Benzyl Compounds', 'Benzylamines', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Enzyme Inhibitors', 'MAO Inhibitors and Diuretics', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB04855,Dronedarone,Dronedaroneis an antiarrhythmic agent used in the reduce the risk of hospitalization in patients with paroxysmal or persistent atrial fibrillation.,"['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'Q12809', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O95069', 'Q14524', 'P48549', 'P51787', 'Q14500', 'Q9UNX9', 'P63252', 'P48050', 'P32418', 'Q9UK17', 'P08588', 'P10827']","Dronedarone is an antiarrhythmic agent that restores normal sinus rhythm and reduces heart rate in atrial fibrillation. In another model, it prevents ventricular tachycardia and ventricular fibrillation.9Dronedarone moderately prolongs the QTc interval by about 10 ms on average.13Dronedarone decreases arterial blood pressure and reduces oxygen consumption. It reduces myocardial contractility with no change in left ventricular ejection fraction. Dronedarone vasodilates coronary arteries through activation of the nitric oxide pathway.9In clinical studies, dronedarone reduced incidence of hospitalizations for acute coronary syndromes and reduced incidence of stroke.3Dronedarone exhibits antiadrenergic effects by reducing alpha-adrenergic blood pressure response to epinephrine and beta 1 and beta 2 responses to isoproterenol.9Dronedarone was shown to inhibit triiodothyronine (T3) signalling by binding to TRα1 but much less so to TRβ1.7The treatment of dronedarone in patients with severe heart failure and left ventricular systolic dysfunction was associated with increased early mortality related to the worsening of heart failure.4In animal studies, the use of dronedarone at doses equivalent to the recommended human doses was associated with fetal harm. In clinical studies and postmarketing reports, dronedarone was shown to cause hepatocellular liver injury and pulmonary toxicities, such as interstitial lung disease, pneumonitis, and pulmonary fibrosis.13Compared to its related compoundamiodarone, dronedarone has a faster onset and offset of actions with a shorter elimination half-life and low tissue accumulation.1,8",CCCCN(CCCC)CCCOC1=CC=C(C=C1)C(=O)C1=C(CCCC)OC2=C1C=C(NS(C)(=O)=O)C=C2,"Atrial fibrillation is the most common type of arrhythmia that is caused by abnormal electrical activity in the atria. In atrial fibrillation, tachyarrhythmia, or fast heart rate, can either be paroxysmal (less than days) or persistent (more than days). Atrial fibrillation causes turbulent and abnormal blood flow through the heart chambers, leading to decreased the effectiveness of the heart to pump blood and an increased likelihood of thrombus formation within the atria which can ultimately dislodge and cause a stroke.Dronedarone achieves heart rate and rhythm control in atrial fibrillation.In vitro, dronedarone decreased the maximum rate of the rise of an action potential in a concentration- and frequency-dependent manner.Cardiac action potentials are generated by ionic currents of multiple voltage-gated ion channels, including potassium, sodium, and calcium channels.Dronedarone is a multichannel blocker that meets the criteria of all four Vaughan Williams antiarrhythmic drug classesbut the contribution of each of these activities to the drug's antiarrhythmic effect is unknown.Dronedarone inhibits rapid Na+ currents rate-dependently (class Ib), non-competitively antagonizes α– and β-adrenergic receptors (class II), blocks K+ outward currents (class III) and blocks slow Ca+ inward currents (class IV).More specifically, it decreases delayed-rectifier K+ current (IKr), slowly activating delayed-rectifier K+ current (IKs), inward rectifier potassium current (IK), peak Na+ current (INa) and L-type Ca+ current (ICa (L)).,Dronedarone ultimately increases refractory periods, decelerates cardiac conduction, and prolongs cardiac action potential and refractory periods.,TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAAlpha-D adrenergic receptorantagonistHumansAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAAlpha-C adrenergic receptorantagonistHumansAPotassium voltage-gated channel subfamily H member inhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-FinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansAPotassium channel subfamily K member inhibitorHumansASodium channel protein type subunit alphainhibitorHumansAG protein-activated inward rectifier potassium channel inhibitorHumansAPotassium voltage-gated channel subfamily KQT member inhibitorHumansAInward rectifier potassium channelinhibitorHumansASodium/calcium exchanger inhibitorHumansAPotassium voltage-gated channel subfamily D member inhibitorHumansUBeta- adrenergic receptorantagonistHumansNThyroid hormone receptor alphainhibitorHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antiarrhythmic agents', 'Antiarrhythmics, Class III', 'Benzofurans', 'Bradycardia-Causing Agents', 'Cardiac Therapy', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Narrow Therapeutic Index Drugs', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'QTc Prolonging Agents']" +DB00278,Argatroban,Argatrobanis a synthetic direct thrombin inhibitor used for the prevention and treatment of thrombosis related to heparin use.,['P00734'],"Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (Ki) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). +Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.",C[C@@H]1CCN([C@H](C1)C(O)=O)C(=O)[C@H](CCCNC(N)=N)NS(=O)(=O)C1=CC=CC2=C1NCC(C)C2,"Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation.TargetActionsOrganismAProthrombininhibitorHumans",[],"['Amides', 'Amino Acids', 'Amino Acids, Basic', 'Amino Acids, Diamino', 'Amino Acids, Essential', 'Amino Acids, Peptides, and Proteins', 'Anticoagulants', 'Antithrombins', 'Blood and Blood Forming Organs', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Hematologic Agents', 'Narrow Therapeutic Index Drugs', 'Piperidines', 'Protease Inhibitors', 'Serine Protease Inhibitors', 'Sulfones', 'Sulfur Compounds', 'Thrombin Inhibitors']" +DB00686,Pentosan polysulfate,Pentosan polysulfateis a sulfated pentosyl polysaccharide used to treat bladder pain and discomfort due to interstitial cystitis.,"['P09038', 'P05230', 'P08620']",Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic effects.,O[C@@H]1CO[C@@H](O[C@@H]2CO[C@@H](O)[C@H](OS(O)(=O)=O)[C@H]2OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O,Pentosan polysulfate is a polymer of xylose hydrogen sulfate and contains two sulfate groups per carbohydrate monomer. It binds Fibroblast growth factors (FGFs) as well as other heparin-binding growth factors. It has been shown to interact also with the heparin-binding site of FGFR-. It inhibits the growth of SW adrenocortical cells transfected with FGF- and tumorigenicity of MCF- breast carcinoma cells transfected with FGF- or FGF-.TargetActionsOrganismAFibroblast growth factor antagonistHumansAFibroblast growth factor antagonistHumansUFibroblast growth factor inhibitorHumans,[],"['Anticoagulants', 'Antivaricose Therapy', 'Carbohydrates', 'Drugs causing inadvertant photosensitivity', 'Genito Urinary System and Sex Hormones', 'Glycosaminoglycans', 'Hematologic Agents', 'Miscellaneous Therapeutic Agents', 'Photosensitizing Agents', 'Polysaccharides', 'Sulfur Acids', 'Sulfur Compounds', 'Sulfuric Acids', 'Urologicals', 'Vasoprotectives']" +DB00823,Ethynodiol diacetate,Ethynodiol diacetateis an oral contraceptive used to prevent pregnancy.,"['P06401', 'P03372']","Ethynodiol Diacetate is used as a female contraceptive. Ethynodiol Diacetate is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Ethynodiol Diacetate tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.",[H][C@@]12CC[C@@](OC(C)=O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CC[C@H](OC(C)=O)C=C3CC[C@@]21[H],"Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Ethynodiol Diacetate will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.TargetActionsOrganismAProgesterone receptoragonistHumansAEstrogen receptor alphaagonistHumans",['Oral Contraceptives'],"['Adrenal Cortex Hormones', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Contraceptive Agents, Hormonal', 'Contraceptives, Oral', 'Contraceptives, Oral, Hormonal', 'Contraceptives, Oral, Synthetic', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hyperglycemia-Associated Agents', 'Norpregnanes', 'Norpregnenes', 'Norsteroids', 'Progestin Contraceptives', 'Progestins', 'Reproductive Control Agents', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB00721,Procaine,"Procaineis a local anesthetic used for anesthesia, peripheral nerve block, and spinal nerve block.","['Q9Y5Y9', 'Q8TCU5', 'P46098', 'Q01959', 'Q15822', 'Q12791', 'Q16558', 'Q9Y691', 'Q9NPA1', 'Q86W47', 'O15554', 'Q92952', 'Q9H2S1', 'Q9UGI6', 'P47712', 'Q86U10', 'P21397', 'P27338', 'P26358', 'Q9Y6K1']","Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine.",CCN(CC)CCOC(=O)C1=CC=C(N)C=C1,"Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansAGlutamate receptor ionotropic, NMDA AantagonistHumansA-hydroxytryptamine receptor AantagonistHumansASodium-dependent dopamine transporterinhibitorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUCalcium-activated potassium channelblockerHumansUCytosolic phospholipase AinhibitorHumansU kDa lysophospholipaseinhibitorHumansUMonoamine oxidaseinhibitorHumansUDNA (cytosine-)-methyltransferase inhibitorHumansUDNA (cytosine-)-methyltransferase AinhibitorHumans",[],"['Acids, Carbocyclic', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Agents that reduce seizure threshold', 'Aminobenzoates', 'Anesthetics', 'Anesthetics, Local', 'Anticholinergic Agents', 'Antidepressive Agents', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Cholinesterase substrates', 'Esters of Aminobenzoic Acid', 'Local Anesthetics (Ester)', 'Methemoglobinemia Associated Agents', 'Monoamine Oxidase Inhibitors', 'Nervous System', 'Nicotinic Antagonists', 'NMDA Receptor Antagonists', 'Ophthalmologicals', 'para-Aminobenzoates', 'Peripheral Nervous System Agents', 'Sensory Organs', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Vasoprotectives']" +DB09070,Tibolone,"Tibolone is a synthetic steroid hormone drug, which is mainly non-selective in its binding profile, acting as an agonist primarily at estrogen receptors (ER), with a preference for ER alpha11.",['P03372'],"Tibolone prevents bone loss and treating post-menopausal symptoms without stimulating the endometrial tissues, which may lead to malignancy. Typical, drugs that treat post-menopausal symptoms such as estrogen, have a proliferative effect on the endometrium, increasing the risk of endometrial carcinoma8. The effects on the bone, brain and vaginal tissues can be explained by the estrogenic activity of tibolone. It is important to note that activity is not expressed in the endometrium. Tibolone behaves differently from estrogen plus progesterone combinations on the breast. Therefore, tibolone can be characterized as a selective estrogen activity regulator1.Tibolone has been demonstrated to be an effective agent in treating symptoms associated with menopause. A 16 week trial in 1189 women examined the effect of tibolone 2.5 mg once daily on climacteric symptoms. Women treated with tibolone showed improvement from baseline in typical menopausal symptoms including hot flashes, sweating, insomnia, and anxiety14.",[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC(=O)CC3)C[C@@]([H])(C)[C@@]21[H],"This drug's effects are owed to the activity of its metabolites in various tissues.Upon ingestion, tibolone is quickly converted into three major metabolites: alpha- and beta-hydroxy-tibolone, which have oestrogenic effects, and theDelta()-isomer, which has progestogenic and androgenic effects. The specific tissue-selective effects of tibolone occur due to the metabolism, regulation of enzymes and receptor activation that varies in different tissues of the body.The bone-conserving effects occur due to estradiol receptor activation, while the progesterone and androgen receptors are not involved in this process. Breast tissue of monkeys is not found to be stimulated after tibolone administration, as occurs with estrogen plus progesterone used in combination. This is explained by the fact that tibolone and its metabolites inhibitsulphatase and beta-hydroxysteroid dehydrogenase(HSD) type I andstimulate sulphotransferase and beta-HSD type II. The combined effects of this process prevent the conversion to active estrogens.In the uterus, the progestogenic activity of theDelta()-metaboliteand the effect on estrogen-inactivating enzymes prevent estrogenic stimulation. The mammary gland is not stimulated in currently used animal models. Tibolone has been shown to regulate estrogenic activity in several tissue types by influencing the availability of estrogenic compounds for the estradiol receptor in a selective manner.Additionally, tibolone modulates cellular homeostasis in the breast by preventing breast tissue proliferation and stimulating cell apoptosis. Tibolone does not stimulate the endometrium because of the action of its highly stable progestogenic metabolite (Delta()-isomer) in combination with an effect on the sulfatase (inhibition)-sulfotransferase (stimulation) system. The estrogenic metabolites of tibolone have direct, favorable effects on the cardiovascular system and, in animal models, this drug has shown no adverse consequences.The tissue-selective effects of tibolone are the result of metabolism, enzyme regulation and receptor activation that vary in different tissues. The bone-preserving effects of tibolone are the result of estradiol receptor activation, while other steroid receptors, mainly the progesterone and androgen receptors, are not involved in this process.In a study of monkeys, breast tissue was not stimulated, which occurs with estrogen and progesterone, because tibolone and its metabolites inhibitsulfatase and beta-hydroxysteroid _dehydrogenase (HSD) type I and stimulate _sulfotransferase and beta-HSD type II. The simultaneous effects of this process halt conversion to active estrogens. Additionally, tibolone affects cellular homeostasis in the breast by preventing proliferation and stimulating apoptosis. Tibolone does not stimulate the endometrium due to the action of the highly stable progestogenic metabolite (Delta()-isomer) in combination with an effect on the sulphatase (inhibition)-sulphotransferase (stimulation) pathway.The levels of tibolone metabolites and the alteration of hormonal activities vary according to the tissue type. In endometrial tissue theΔ-isomerfunctions as a progestagen, however, in the brain and liver, it shows androgenic effects. In breast tissue, the primary actions of tibolone are strong inhibition of sulfatase activity and weak inhibition of β-hydroxysteroid dehydrogenase activity, which leads to blocking the conversion estrone sulfate to E.TargetActionsOrganismAEstrogen receptor alphaantagonistagonistHumans",[],"['Anabolic Agents', 'Antineoplastic Agents, Hormonal', 'Cardiovascular Agents', 'Estrogen Receptor Modulators', 'Estrogens', 'Estrogens, Antiestrogens, and Estrogen Agonist-Antagonists', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormone Antagonists', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Norpregnanes', 'Norsteroids', 'Sex Hormones and Modulators of the Genital System', 'Steroids']" +DB06154,Pentaerythritol tetranitrate,"Pentaerythritol tetranitrate is the nitrate ester of pentaerythritol that possesses explosive properties. When mixed with a plasticizer, this chemical forms a plastic explosive. It is recognized by the FDA to be a coronary vasodilator in the treatment of heart conditions such as angina9.","['P69905', 'P68871']","Organic nitrate which causes systemic vasodilation, decreasing cardiovascular preload15.Nitrate enters vascular smooth muscle and converted to nitric oxide (NO) which acts as a cellular messenger, leading to activation of cyclic GMP and, therefore, vasodilation15.The nitrovasodilator group of drugs relaxes most smooth muscles in the body, including those in the walls of arteries and veins, and selectively dilate large coronary vessels12. Lower doses of nitrates increase coronary blood flow without significantly affecting systemic arterial pressure. Higher doses, especially if repeated frequently, decrease systolic and diastolic blood pressure as well as cardiac output, which can result in a headache, weakness, dizziness, and the activation of compensatory sympathetic reflexes, including tachycardia and peripheral arteriolar vasoconstriction5.Smooth muscles in the bronchi, biliary tract, gastrointestinal tract, ureters, and uterus also can be relaxed by nitrovasodilators. PETN seems to be unique among the long-acting nitrovasodilators in that patients do not demonstrate tolerance to treatment, which results in sustained vasodilation in humans with continuous PETN treatment14.Important to note is that this drug is devoid of induction of oxidative stress and related side-effects such as endothelial dysfunction or tolerance to nitrates. Some of these effects are related to special pharmacokinetics of PETN, but upon chronic administration, PETN also induces antioxidative pathways at the genomic level, resulting in increased expression of hemeoxygenase-1 (HO-1)and ferritin, both possessing highly protective properties. There is good experimental evidence that at least part of the beneficial profile of long-term treatment with this drug is based on the activation of theheme oxygenase-1/ferritinsystem16.",[O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O,"Pentaerythritol tetranitrate is the lipid soluble polyol ester of nitric acid belonging to the family ofnitro-vasodilators. Pentaerythritol tetranitrate releases free nitric oxide (NO) after the denitration reaction, which triggers NO-dependent signaling transduction involving solubleguanylate cyclase (sGC). Nitric oxide binds reversibly to the ferrous-heme center of sGC, causing conformational change and activating the enzyme. This enzyme activation results in increased cellular concentrations of _cyclic guanosine monophosphate _(cGMP) within the vascular smooth muscle, resulting in vasodilation mediated by cGMP-dependent protein kinases. Additionally, this agent causes dose-dependent arterial and venous bed.TargetActionsOrganismAHemoglobin subunit alphaagonistHumansAHemoglobin subunit betaagonistHumansNFree radicalsantagonistHumans",[],"['Alcohols', 'Antianginal Agents', 'Carbohydrates', 'Cardiac Therapy', 'Cardiovascular Agents', 'Drugs that are Mainly Renally Excreted', 'Fibrin Modulating Agents', 'Glycols', 'Hematologic Agents', 'Organic Nitrates', 'Polysaccharides', 'Propylene Glycols', 'Vasodilating Agents', 'Vasodilators Used in Cardiac Diseases']" +DB00800,Fenoldopam,Fenoldopamis a dopamine D1 receptor agonist used for the short term management of hypertension.,"['P21918', 'P21728', 'P35368', 'P25100', 'P35348', 'P18089', 'P18825', 'P08913']","Fenoldopam is an agonist at D1-like dopamine receptors, binds to α2-adrenoceptors, increasing renal blood flow.",OC1=CC=C(C=C1)C1CNCCC2=C(Cl)C(O)=C(O)C=C12,"Fenoldopam is a rapid-acting vasodilator. It is an agonist for D-like dopamine receptors and binds with moderate affinity to α-adrenoceptors. It has no significant affinity for D-like receptors, αand β-adrenoceptors, HTand HTreceptors, or muscarinic receptors. Fenoldopam is a racemic mixture with the R-isomer responsible for the biological activity. The R-isomer has approximately -fold higher affinity for D-like receptors than does the S-isomer. In non-clinical studies, fenoldopam had no agonist effect on presynaptic D-like dopamine receptors, or α or β -adrenoceptors, nor did it affect angiotensin-converting enzyme activity. Fenoldopam may increase norepinephrine plasma concentration.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansUAlpha-B adrenergic receptorinhibitorHumansUAlpha-D adrenergic receptorinhibitorHumansUAlpha-A adrenergic receptorinhibitorHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumans",[],"['Adrenergic and Dopaminergic Agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzazepines', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Dopamine Agents', 'Dopamine Agonists', 'Dopamine D1 Receptor Agonists', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Vasodilating Agents']" +DB06725,Lornoxicam,"Lornoxicamis an NSAID indicated in the treatment of mild to moderate pain, as well as rheumatoid arthritis and osteoarthritis.","['P23219', 'P35354']","Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events.",CN1C(C(=O)NC2=CC=CC=N2)=C(O)C2=C(C=C(Cl)S2)S1(=O)=O,"Like other NSAIDS, lornoxicam's anti-inflammatory and analgesic activity is related to its inhibitory action on prostaglandin and thromboxane synthesis through the inhibition of both COX- and COX-. This leads to the reduction of inflammation, pain, fever, and swelling, which are mediated by prostaglandins. However, the exact mechanism of lornoxicam, like that of the other NSAIDs, has not been fully determined.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Oxicams', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Sulfur Compounds', 'Thiazines']" +DB04725,Licofelone,"Developed by the German pharmaceutical company, Merckle GmbH, together with EuroAlliance partners Alfa Wassermann and Lacer, licofelone (ML3000) is a dual COX/LOX inhibitor and the first member of this new class of analgesic and anti-inflammatory drugs. It is currently under evaluation as a treatment for osteoarthritis (OA), the most common form of arthritis. Although phase III trials have been successfully completed in OA patients no dates for regulatory submission have yet been given.","['P09917', 'P35354', 'Q9NZK7']",Licofelone belongs to a novel class of dual-acting anti-inflammatory drugs called COX/LO inhibitors. This group of drugs simultaneously inhibits the enzymes cyclooxygenase (COX) and 5-lipoxygenase (LO).,CC1(C)CN2C(CC(O)=O)=C(C(=C2C1)C1=CC=CC=C1)C1=CC=C(Cl)C=C1,"Licofelone, through combined -LOX/COX-inhibition, reduces levels of inflammatory prostaglandins and leukotrienes.TargetActionsOrganismUArachidonate -lipoxygenaseNot AvailableHumansUProstaglandin G/H synthase Not AvailableHumansUGroup IIE secretory phospholipase ANot AvailableHumans",[],"['Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antirheumatic Agents', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Lipoxygenase Inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'UGT1A3 substrates']" +DB01296,Glucosamine,Glucosamineis a common ingredient in nutritional supplements used for the relief of joint pain.,"['P01579', 'Q04206']","The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility.11A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.6",N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O,"The mechanism of action of glucosamine in joint health is unclear,however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage,glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma,,and Nuclear factor kappa B subunit (NF-κB p),,improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time.TargetActionsOrganismUInterferon gammainhibitorHumansUTranscription factor pinhibitorHumans",[],"['Amino Sugars', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Carbohydrates', 'Hexosamines', 'Musculo-Skeletal System']" +DB00814,Meloxicam,"Meloxicamis an NSAID used to treat osteoarthritis in adults, rheumatoid arthritis in adults, and juvenile rheumatoid arthritis in pediatrics.","['P35354', 'P23219']","Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever.1Prostaglandins are substances that contribute to inflammation.7This drug also exerts preferential actions against COX-23, which may reduce the possible gastrointestinal effects of this drug.In humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate(ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as aquaporin-1 expression.1As with other NSAIDS, prolonged use of meloxicum can result in renal or cardiovascular impairment or thrombotic cardiovascular events.10A note on gastrointestinal effectsAs meloxicam preferentially inhibits COX-2, it is thought to cause less gastrointestinal irritation compared to other NSAIDS. Despite this, it still carries a risk of gastric inflammation, bleeding and ulceration.5,10In one study, patients on meloxicam suffered from gastrointestinal symptoms at a rate of 13% compared to 19% of those ondiclofenac. GI events were found to be less severe in the meloxicam-treated patients.1",CN1C(C(=O)NC2=NC=C(C)S2)=C(O)C2=C(C=CC=C2)S1(=O)=O,"Meloxicam inhibits prostaglandin synthetase (cylooxygenase and ) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms.As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-, but also exerts some activity against COX-, causing gastrointestinal irritation.,TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amides', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anesthetics', 'Anesthetics, Local', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Nervous System', 'Other Nonsteroidal Anti-inflammatory Agents', 'Oxicams', 'Peripheral Nervous System Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Sulfur Compounds', 'Thiazines', 'Thiazoles']" +DB08845,Oxogluric acid,"Oxogluric acid (α-Ketoglutarate) is not approved for any indication in the world but is an investigational drug in the United States. In the United States a phase I clinical trial is investigating whether oxogluric acid precursors found in nutritional supplements can benefit patients with the metabolic disorder propionic acidemia. Oxogluric acid is sold as a dietary supplement to athletes to improve their performance by helping to remove excess ammonia, but it is not officially approved for this indication and only experimental studies have shown a reduction in ammonia by oxogluric acid in hemodialysis patients. Physiologically, oxogluric acid acts in the Krebs cycle as an intermediate, is involved in transamination reactions during the metabolism of amino acids, forms glutamic acid by combining with ammonia, and reduces nitrogen by combining with it as well. Several experimental studies have also shown that administration of oxogluric acid helped attenuate the decreased synthesis of muscle protein that is often seen post-surgery.",['P00509'],"All of the physiological roles of alpha-ketoglutarate have not been determined. What is known is that alpha-keotglutarate is involved in the Krebs cycle, transamination reactions, and promotes muscle synthesis.",OC(=O)CCC(=O)C(O)=O,"The exact mechanisms of action for α-Ketoglutarate have not yet been elucidated. Some of α-Ketoglutarate’s actions include acting in the Krebs cycle as an intermediate, transamination reactions during the metabolism of amino acids, forming glutamic acid by combining with ammonia, and reducing nitrogen by combining with it as well. Concerning α-Ketoglutarate’s actions with ammonia, it is proposed that α-Ketoglutarate can help patients with propionic academia who have high levels of ammonia and low levels of glutamine/glutamate in their blood. Because endogenous glutamate/glutamine is produced from α-Ketoglutarate, propionic acidemia patients have impaired production of α-Ketoglutarate and supplementation of α-Ketoglutarate should improve the condition of these patients. Several other experimental studies have also shown that administration of α-Ketoglutarate in parenteral nutrition given to post-operative patients helped attenuate the decreased synthesis of muscle protein that is often seen after a surgery. This decreased muscle synthesis is speculated to be due to too low α-Ketoglutarate levels.TargetActionsOrganismUAspartate aminotransferaseNot AvailableEscherichia coli (strain K)",[],"['Acids, Acyclic', 'Dicarboxylic Acids', 'Glutarates', 'Keto Acids', 'Ketoglutaric Acids']" +DB04942,Tamibarotene,"Tamibarotene is a novel synthetic retinoid for acute promyelocytic leukaemia (APL). Tamibarotene is currently approved in Japan for treatment of recurrent APL, and is undergoing clinical trials in the United States.","['P10276', 'P10826']","Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials.",CC1(C)CCC(C)(C)C2=C1C=CC(NC(=O)C1=CC=C(C=C1)C(O)=O)=C2,Tamibarotene is a specific agonist for retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR).TargetActionsOrganismARetinoic acid receptor alphaagonistHumansARetinoic acid receptor betaagonistHumans,[],"['Acids, Carbocyclic', 'Benzene Derivatives', 'Naphthalenes']" +DB00580,Valdecoxib,Valdecoxibis a COX-2 inhibitor used to treat osteoarthritis and dysmenorrhoea.,"['P35354', 'P00918', 'P07451']","Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib is used for its anti-inflammatory, analgesic, and antipyretic activities in the management of osteoarthritis (OA) and for the treatment of dysmenorrhea or acute pain. Unlike celecoxib, valdecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism.",CC1=C(C(=NO1)C1=CC=CC=C1)C1=CC=C(C=C1)S(N)(=O)=O,"Both COX- and COX- catalyze the conversion of arachidonic acid to prostaglandin (PG) H, the precursor of PGs and thromboxane. Valdecoxib selectively inhibits the cyclooxygenase- (COX-) enzyme, important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, valdecoxib does not inhibit platelet aggregation.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amides', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Benzene Derivatives', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Peripheral Nervous System Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'UGT1A9 Substrates']" +DB00469,Tenoxicam,Tenoxicamis an anti inflammatory analgesic used to treat mild to moderate pain as well as the signs and symptoms of rheumatoid arthritis and osteoarthritis.,"['P35354', 'P23219']","Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.",CN1C(C(=O)NC2=CC=CC=N2)=C(O)C2=C(C=CS2)S1(=O)=O,"The antiinflammatory effects of tenoxicam may result from the inhibition of the enzyme cycooxygenase and the subsequent peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, their inhibition accounts for the peripheral analgesic effects of tenoxicam. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT3/SLC22A8 Inhibitors', 'Other Nonsteroidal Anti-inflammatory Agents', 'Oxicams', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Sulfur Compounds', 'Thiazines']" +DB01178,Chlormezanone,A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm.,['P30536'],Chlormezanone is a non-benzodiazepine muscle relaxant. It was discontinued worldwide in 1996 by its manufacturer due to confirmed serious and rare cutaneous reactions (toxic epidermal necrolysis).,CN1C(C2=CC=C(Cl)C=C2)S(=O)(=O)CCC1=O,"Chlormezanone binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.TargetActionsOrganismATranslocator proteinagonistHumans",[],"['Anti-Anxiety Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Oxazol, Thiazine, and Triazine Derivatives', 'Peripheral Nervous System Agents', 'Psychotropic Drugs', 'Sulfur Compounds', 'Thiazines', 'Tranquilizing Agents']" +DB11753,Rifamycin,Rifamycinis an antibacterial used to treat traveler's diarrhea.,"['P0A8V2', 'P0A7Z4', 'P0A8T7']","Rifamycin is known to be effective against Gram-positive and Gram-negative pathogens and mycobacteria. It is very effective againstE. colireporting a MIC90 of 64-128 mcg/ml without showing cross-resistance with other antimicrobial agents.4The specific indication of rifamycin is extremely important as ther were previous reports that indicated a high risk factor in the generation of resistantE. colistrains in patients with inflammatory bowel disease.13In clinical trials, rifamycin was tested in a randomized clinical trial of travellers' coming from Mexico and Guatemala. In this trial, rifamycin was proven to significantly reduce the symptoms of travellers' diarrhea.12",CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C)C(O)=C4C(O)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C=C(O)C4=C3C2=O,"Rifamycins, as well as all the other members of this group, present an antibacterial mechanism of action related to the inhibition of RNA synthesis. This mechanism of action is done by the strong binding to the DNA-dependent RNA polymerase of prokaryotes. The inhibition of the RNA synthesis is thought to be related with the initiation phase of the process and to involve stacking interactions between the naphthalene ring and the aromatic moiety in the polymerase. As well, it has been suggested that the presence of zinc atoms in the polymerase allows for the binding of phenolic -OH groups of the naphthalene ring.In eukaryotic cells, the binding is significantly reduced making them at least to , times less sensitive to the action of rifamycins. The members of the rifamycin family present the same mechanism of action and the structural modifications are usually related to pharmacokinetic properties as well as to the interaction with eukaryotic cells.TargetActionsOrganismADNA-directed RNA polymerase subunit betabinderEscherichia coli (strain K)ADNA-directed RNA polymerase subunit alphabinderEscherichia coli (strain K)ADNA-directed RNA polymerase subunit beta'binderEscherichia coli (strain K)",[],"['Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics for Topical Use', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Antirheumatic Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Drugs for Treatment of Tuberculosis', 'Heterocyclic Compounds, Fused-Ring', 'Intestinal Antiinfectives', 'Lactams, Macrocyclic', 'MATE 1 Inhibitors', 'MATE inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Ophthalmologicals', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Otologicals', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Rifamycin Antibacterial', 'Rifamycins', 'Sensory Organs']" +DB06736,Aceclofenac,"Aceclofenac is an oral non-steroidal anti-inflammatory drug (NSAID) with marked anti-inflammatory and analgesic properties used to treat osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. It is reported to have a higher anti-inflammatory action or at least comparable effects than conventional NSAIDs in double-blind studies2,3,5. Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever. Aceclofenac belongs to BCS Class II as it possesses poor aqueous solubility2. It displays high permeability to penetrate into synovial joints where in patients with osteoarthritis and related conditions, the loss of articular cartilage in the area causes joint pain, tenderness, stiffness, crepitus, and local inflammation1. Aceclofenac is also reported to be effective in other painful conditions such as dental and gynaecological conditions7. In 1991, aceclofenac was developed as an analog of a commonly prescribed NSAID,Diclofenac, via chemical modification in effort to improve the gastrointestinal tolerability of the drug. It is a more commonly prescribed drug in Europe.","['P35354', 'P23219']","Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM2. Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF)1,2. It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils8. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects1.",OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl,"Through COX- inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E (PGE), IL-β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL- is thought to be mediated by diclofenac converted from aceclofenac. Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes. In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CDL), which is a cell adhesion molecule expressed on lymphocytes. Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL- production and activity. The chrondroprotective effects are generated by '-hydroxyaceclofenac which suppresses IL- mediated production of promatrix metalloproteinase- and metalloproteinase- and interferes with the release of proteoglycan from chrondrocytes,,.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Acetic Acid Derivatives and Related Substances', 'Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Peripheral Nervous System Agents', 'Phenylacetates', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain']" +DB00214,Torasemide,"Torasemideis a diuretic used to treat hypertension and edema associated with heart failure, renal failure, or liver disease.","['P55011', 'Q13621']","It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control.2This effect is obtained by the increase in the excretion of urinary sodium and chloride.3Several reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy withfurosemideandspironolactoneand it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function.3Above the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action.2Torasemide has been shown to reduce extracellular fluid volume and blood pressure in hypertensive patients suffering from chronic kidney disease. As well, some reports have indicated that torasemide can reduce myocardial fibrosis by reducing the collagen accumulation. This effect is suggested to be related to the decrease in aldosterone which in order has been shown to reduce the production of the enzyme procollagen type I carboxy-terminal proteinase which is known to be overexpressed in heart failure patients.1",CC(C)NC(=O)NS(=O)(=O)C1=C(NC2=CC=CC(C)=C2)C=CN=C1,"As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface.This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule.Torasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B and thromboxane A and a reduction on the aldosterone receptor binding.,TargetActionsOrganismASolute carrier family member inhibitorHumansASolute carrier family member inhibitorHumans",[],"['Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diuretics', 'High-Ceiling Diuretics', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis at Loop of Henle', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Non Potassium Sparing Diuretics', 'OATP1B1/SLCO1B1 Substrates', 'Ototoxic agents', 'Pyridines', 'Sodium Potassium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB00946,Phenprocoumon,Phenprocoumonis an anticoagulant drug used for the prevention of thrombosis.,['Q9BQB6'],"Phenprocoumon, a coumarin anticoagulant, thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as phenprocoumon have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae.",CCC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2,"Phenprocoumon inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.TargetActionsOrganismAVitamin K epoxide reductase complex subunit inhibitorHumans",[],"['4-Hydroxycoumarins', 'Anticoagulants', 'Benzopyrans', 'Blood and Blood Forming Organs', 'Coumarins', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Pyrans', 'Vitamin K Antagonists', 'Vitamin K Inhibitors']" +DB00520,Caspofungin,Caspofunginis an echinocandin used to treat a variety of fungal infections.,['A2QLK4'],"Caspofungin is an antifungal drug, and belongs to a new class termed the echinocandins. It is used to treatAspergillusandCandidainfection, and works by inhibiting cell wall synthesis. Antifungals in the echinocandin class inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-beta glucan synthase. There is a potential for resistance development to occur, howeverin vitroresistance development to Caspofungin by Aspergillus species has not been studied.",[H][C@@]12C[C@@H](O)CN1C(=O)[C@@H](NC(=O)[C@]([H])(C[C@@H](O)[C@@H](NCCN)NC(=O)[C@@H]1[C@@H](O)CCN1C(=O)[C@@H](NC(=O)[C@@H](NC2=O)[C@H](O)[C@@H](O)C1=CC=C(O)C=C1)[C@H](O)CCN)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@@H](C)O,"Caspofungin inhibits the synthesis of beta-(,)-D-glucan, an essential component of the cell wall ofAspergillusspecies andCandidaspecies. beta-(,)-D-glucan is not present in mammalian cells. The primary target is beta-(,)-glucan synthase.TargetActionsOrganismA,-beta-glucan synthase component FKSinhibitorAspergillus niger (strain CBS . / FGSC A)",[],"['Amino Acids, Peptides, and Proteins', 'Anti-Infective Agents', 'Antifungal Agents', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Echinocandin Antifungal', 'Echinocandins', 'Enzyme Inhibitors', 'Lipids', 'Lipopeptides', 'OAT1/SLC22A6 inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein inhibitors', 'Peptides', 'Peptides, Cyclic']" +DB00362,Anidulafungin,Anidulafunginis an antifungal used in the treatment of several types of candida infections.,['A2QLK4'],"Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product ofAspergillus nidulans. Anidulafungin is an echinocandin, a class of antifungal drugs that inhibits the synthesis of 1,3-β-D-glucan, an essential component of fungal cell walls. Anidulafungin is active in vitro against manyCandida, as well as someAspergillus. Like other echinocandins, anidulafungin is not active againstCryptococcus neoformans,Trichosporon,Fusarium, or zygomycetes.",[H][C@]1(NC(=O)[C@@H](NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)[C@H](C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)[C@@H](C)CN2C1=O)NC(=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CC=C(OCCCCC)C=C1)[C@@H](C)O)[C@H](O)[C@@H](O)C1=CC=C(O)C=C1)[C@@H](C)O,"Anidulafungin is a semi-synthetic echinocandin with antifungal activity. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of ,-β-D-glucan, an essential component of the fungal cell wall, ultimately leading to osmotic instability and cell death.TargetActionsOrganismA,-beta-glucan synthase component FKSinhibitorAspergillus niger (strain CBS . / FGSC A)",[],"['Amino Acids, Peptides, and Proteins', 'Anti-Infective Agents', 'Antifungal Agents', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Echinocandin Antifungal', 'Echinocandins', 'Peptides', 'Peptides, Cyclic']" +DB01263,Posaconazole,Posaconazoleis a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients.,['P10613'],"Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.",CC[C@@H]([C@H](C)O)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=NC=N3)(C2)C2=C(F)C=C(F)C=C2)C=C1,"As a triazole antifungal agent, posaconazole exerts its antifungal activity through blockage of the cytochrome P- dependent enzyme, sterol α-demethylase, in fungi by binding to the heme cofactor located on the enzyme. This leads to the inhibition of the synthesis of ergosterol, a key component of the fungal cell membrane, and accumulation of methylated sterol precursors. This results in inhibition of fungal cell growth and ultimately, cell death.TargetActionsOrganismACytochrome P antagonistYeast",[],"['14-alpha Demethylase Inhibitors', 'Anti-Infective Agents', 'Antifungal Agents', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'Antiparasitic Agents', 'Antiprotozoals', 'Azole Antifungals', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Steroid Synthesis Inhibitors', 'Triazole and tetrazole derivatives', 'Triazole Derivatives', 'Trypanocidal Agents']" +DB00697,Tizanidine,Tizanidineis an alpha-2 adrenergic agonist used for the short-term treatment of muscle spasticity.,"['Q9Y2I1', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","A note on spasticitySpasticity is an increase in muscle accompanied by uncontrolled, repetitive contractions of skeletal muscles which are involuntary. +The patient suffering from muscle spasticity may have reduced mobility and high levels of pain, contributing to poor quality of life and problems performing activities of personal hygiene and care7.General effectsTizanidine is a rapidly acting drug used for the relief of muscle spasticity when it is required for performing specific activities. It acts as an agonist at Alpha-2 adrenergic receptor sites and relieves symptoms of muscle spasticity, allowing the continuation of normal daily activities. In animal models, tizanidine has not been shown to exert direct effects on skeletal muscle fibers or the neuromuscular junction, and has shown no significant effect on monosynaptic spinal reflexes (consisting of the communication between only 1 sensory neuron and 1 motor neuron)10. The frequency of muscle spasm and clonus are shown to be decreased by tizanidine9. Tizanidine shows a stronger action on polysynaptic reflexes, which involve several interneurons (relay neurons) communicating with motor neurons stimulating muscle movement10.Effects on blood pressure and heart rateThis drug decreases heart rate and blood pressure in humans4,6. Despite this, rebound hypertension and tachycardia along with increased spasticity can occur when tizanidine is abruptly discontinued8.",ClC1=C(NC2=NCCN2)C2=NSN=C2C=C1,"Tizanidine reduces spasticity by causing presynaptic inhibition of motor neurons via agonist actions at Alpha- adrenergic receptor sites. +This drug is centrally acting and leads to a reduction in the release of excitatory amino acids like glutamate and aspartate, which cause neuronal firing that leads to muscle spasm. The above reduction and excitatory neurotransmitter release results in presynaptic inhibition of motor neurons. The strongest effect of tizanidine has been shown to occur on spinal polysynaptic pathways. The anti-nociceptive and anticonvulsant activities of tizanidine may also be attributed to agonist action on Alpha- receptors. Tizanidine also binds with weaker affinity to the Alpha- receptors, explaining its slight and temporary effect on the cardiovascular system.TargetActionsOrganismNNischarinagonistHumansUAlpha- adrenergic receptorsagonistHumansUAlpha- adrenergic receptorsagonistHumans",['Withdrawal From Addictive Substance; Detoxification'],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Analgesics', 'Anticonvulsants', 'Autonomic Agents', 'Bradycardia-Causing Agents', 'Central alpha-2 Adrenergic Agonist', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Imidazoles', 'Imidazolines', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Narrow Therapeutic Index Drugs', 'Neuromuscular Agents', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sensory System Agents']" +DB00589,Lisuride,"An ergot derivative that acts as an agonist at dopamine D2 receptors (dopamine agonists). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (serotonin agonists).","['P14416', 'P35462', 'P21917', 'P28223', 'P28335', 'P21728', 'P21918', 'P08908', 'P28221', 'P41595', 'P28222', 'P08913', 'P18089', 'P18825', 'P34969']","There is evidence that lisuride lowers prolactin levels and, in low doses, prevents migraine attacks.",[H][C@@]12CC3=CNC4=CC=CC(=C34)C1=C[C@@H](CN2C)NC(=O)N(CC)CC,Lisuride is an anti-Parkinson drug chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride binds to the -HT(A) and -HT(A/C) receptors. It is also thought to bind to the dopamine receptor and to act as a dopamine agonist. Evidence has also emerged that Lisuride also binds to the Histamine H receptor.TargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansA-hydroxytryptamine receptor AagonistHumansA-hydroxytryptamine receptor CagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor DagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor BagonistHumansUAlpha-A adrenergic receptorother/unknownHumansUAlpha-B adrenergic receptorother/unknownHumansUAlpha-C adrenergic receptorother/unknownHumansU-hydroxytryptamine receptor Not AvailableHumans,[],"['Agents that produce hypertension', 'Alkaloids', 'Analgesics', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Antimigraine Preparations', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Dopamine Antagonists', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Ergot-derivative Dopamine Receptor Agonists', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Prolactine Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Serotonin Receptor Antagonists']" +DB00918,Almotriptan,Almotriptanis a 5-HT1B/1D receptor agonist used to treat migraines.,"['P28221', 'P28222']","Almotriptan is a selective 5-hydroxytryptamine receptor subtype agonist indicated for the acute treatment of migraine attacks with or without aura in adults. Almotriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Almotriptan is an agonist for a vascular 5-hydroxytryptamine receptor subtype (probably a member of the 5-HT1Dfamily) having only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3or 5-HT4receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Almotriptan also activates 5-HT1receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Almotriptan in humans.",CN(C)CCC1=CNC2=C1C=C(CS(=O)(=O)N1CCCC1)C=C2,Almotriptan binds with high affinity to human -HTBand -HTDreceptors leading to cranial blood vessel constriction.TargetActionsOrganismU-hydroxytryptamine receptor DagonistHumansU-hydroxytryptamine receptor BagonistHumans,[],"['Agents that produce hypertension', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Biogenic Amines', 'Biogenic Monoamines', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Migraine Disorders', 'Monoamine Oxidase A Substrates', 'Nervous System', 'Neurotransmitter Agents', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Triptans']" +DB00706,Tamsulosin,"Tamsulosinis an alpha-1A and alpha-1B adrenergic receptor antagonist used to treat benign prostatic hyperplasia, ureteral stones, prostatitis, and female voiding dysfunction.","['P35348', 'P25100', 'P35368']","Tamsulosin is an alpha adrenoceptor blocker with specificity for the alpha-1A and alpha-1D subtypes, which are more common in the prostate and submaxillary tissue.1The final subtype, alpha-1B, are most common in the aorta and spleen.1Tamsulosin binds to alpha-1A receptors 3.9-38 times more selectively than alpha-1B and 3-20 times more selectively than alpha-1D.1This selectivity allows for a significant effect on urinary flow with a reduced incidence of adverse reactions like orthostatic hypotension.1",CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC(=C(OC)C=C1)S(N)(=O)=O,"Tamsulosin is a blocker of alpha-A and alpha-D adrenoceptors.Label,About % of the alpha- adrenoceptors in the prostate are of the alpha-A subtype.LabelBy blocking these adrenoceptors, smooth muscle in the prostate is relaxed and urinary flow is improved.LabelThe blocking of alpha-D adrenoceptors relaxes the detrusor muscles of the bladder which prevents storage symptoms.The specificity of tamsulosin focuses the effects to the target area while minimizing effects in other areas.LabelTargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Amides', 'Benzene Derivatives', 'Benzenesulfonamides', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Benign Prostatic Hypertrophy', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Gynecological Antiinfectives and Antiseptics', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Peripheral alpha-1 blockers', 'Selective Alfa-1-adrenergic Blocking Agents', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Urological Agents', 'Urologicals']" +DB00568,Cinnarizine,"Cinnarizineis a drug used for the management of labyrinthine disorder symptoms, including vertigo, tinnitus, nystagmus, nausea, and vomiting.","['P35367', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'O43497', 'O95180', 'Q9P0X4', 'P14416', 'P21728', 'P21918', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Cinnarizine is an antihistamine and a calcium channel blocker. Histamines mediate a number of activities such as contraction of smooth muscle of the airways and gastrointestinal tract, vasodilatation, cardiac stimulation, secretion of gastric acid, promotion of interleukin release and chemotaxis of eosinophils and mast cells. Competitive antagonists at histamine H1 receptors may be divided into first (sedating) and second (non-sedating) generation agents. Some, such as Cinnarizine also block muscarinic acetylcholine receptors and are used as anti-emetic agents. Cinnarizine through its calcium channel blocking ability also inhibits stimulation of the vestibular system.",C(\C=C\C1=CC=CC=C1)N1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1,"Cinnarizine inhibits contractions of vascular smooth muscle cells by blocking L-type and T-type voltage gated calcium channels. Cinnarizine has also been implicated in binding to dopamine D receptors, histamine H receptors, and muscarinic acetylcholine receptors.TargetActionsOrganismAHistamine H receptorantagonistHumansAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-FinhibitorHumansAVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansNDopamine D receptorother/unknownHumansUD() dopamine receptorbinderHumansUMuscarinic acetylcholine receptorbinderHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antivertigo Preparations', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotransmitter Agents', 'Piperazines', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB01162,Terazosin,Terazosinis an alpha-1 adrenergic antagonist used in the treatment of symptomatic benign prostatic hyperplasia and management of hypertension.,"['P35348', 'P35368', 'P25100', 'P01137', 'Q12809', 'Q9H252', 'Q9NS40']","Terazosin is a quinazoline derivative alpha-1-selective adrenergic blockerLabel1,2.",COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1CCCO1,"Terazosin is selective for alpha--adrenoceptors but not their individual subtypes,. Inhibition of these alpha--adrenoceptors results in relaxation of smooth muscle in blood vessels and the prostate, lowering blood pressure and improving urinary flow,,,. Smooth muscle cells accounts for roughly % of the volume of the prostate and so their relaxation reduces pressure on the urethra.It has also been shown that catecholamines induce factors responsible for mitogenesis and alpha--adrenergic receptor blockers inhibit this effect.A final long term mechanism of terazosin and other alpha--adrenergic receptor blockers is the induction of apoptosis of prostate cells. Treatment with terazosin enhances the expression of transforming growth factor beta- (TGF-beta), which upregulates pkip, and the caspase cascade,.TargetActionsOrganismAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansAAlpha-D adrenergic receptorantagonistHumansATransforming growth factor beta-inducerHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUPotassium voltage-gated channel subfamily H member inhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Drugs Used in Benign Prostatic Hypertrophy', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Peripheral alpha-1 blockers', 'Quinazolines', 'Urological Agents', 'Urologicals']" +DB00824,Enprofylline,"Enprofylline is a derivative of theophylline which shares bronchodilator properties. Enprofylline is used in asthma, chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy. Long-term enprofylline administration may be associated with elevation in liver enzyme levels and unpredictable blood levels.","['Q07343', 'P29275', 'P27815', 'P30542', 'P29274', 'P0DMS8']","Enprofylline is a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine. It antagonizes erythrocyte phosphodiesterase, increasing cAMP activity.",CCCN1C2=C(NC=N2)C(=O)NC1=O,"Enprofylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, enprofylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity.TargetActionsOrganismAcAMP-specific ','-cyclic phosphodiesterase BinhibitorHumansAAdenosine receptor AbantagonistHumansAcAMP-specific ','-cyclic phosphodiesterase AinhibitorHumansUAdenosine receptor AinhibitorHumansUAdenosine receptor AainhibitorHumansUAdenosine receptor AinhibitorHumans",[],"['Adenosine A2 Receptor Antagonists', 'Alkaloids', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Heterocyclic Compounds, Fused-Ring', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P1 Receptor Antagonists', 'Purines', 'Purinones', 'Respiratory System Agents']" +DB00936,Salicylic acid,"Salicylic acidis an acid used to treat acne, psoriasis, calluses, corns, keratosis pilaris, and warts.","['P23219', 'P35354', 'Q04828']","Salicylic acid treats acne by causing skin cells to slough off more readily, preventing pores from clogging up. This effect on skin cells also makes salicylic acid an active ingredient in several shampoos meant to treat dandruff. Use of straight salicylic solution may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock. Subsalicylate in combination with bismuth form the popular stomach relief aid known commonly as Pepto-Bismol. When combined the two key ingredients help control diarrhea, nausea, heartburn, and even gas. It is also very mildly anti-biotic.",OC(=O)C1=CC=CC=C1O,"Salicylic acid directly irreversibly inhibits COX- and COX- to decrease conversion of arachidonic acid to precursors of prostaglandins and thromboxanes. Salicylate's use in rheumatic diseases is due to it's analgesic and anti-inflammatory activity. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Salicylic acid allows cells of the epidermis to more readily slough off. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid competitively inhibits oxidation of uridine--diphosphoglucose (UDPG) with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of the glucuronyl group of uridine--phosphoglucuronic acid (UDPGA) to a phenolic acceptor. Inhibition of mucopoly saccharide synthesis is likely responsible for the slowing of wound healing with salicylates.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansUAldo-keto reductase family member CinhibitorHumans",['Keratolysis'],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Infective Agents', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antifungal Agents', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Benzene Derivatives', 'Benzoates', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Hydroxy Acids', 'Hydroxybenzoates', 'Keratolytic Agents', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP2B1/SLCO2B1 substrates', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenols', 'Salicylates', 'Salicylic Acid and Derivatives', 'Sclerosing Solutions', 'Sensory Organs', 'Sensory System Agents']" +DB00716,Nedocromil,Nedocromilis a pyrano quinoline used to treat allergic conjunctivitis.,"['Q9Y271', 'Q9NS75', 'P21462', 'Q13258', 'P07900']",Nedocromil is a anti-inflammatory agent and can be administered directly to the bronchial mucosa. It has significant inhibitory effect on allergen-induced early and late asthmatic reactions and on bronchial hyperresponsiveness.,CCCC1=C2N(CC)C(=CC(=O)C2=CC2=C1OC(=CC2=O)C(O)=O)C(O)=O,"Nedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D and leukotrienes c from different types of cells in the lumen and mucosa of the bronchial tree. These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-geneñrelated peptides. The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not posess any bronchodilator, antihistamine, or corticosteroid activity.TargetActionsOrganismACysteinyl leukotriene receptor antagonistHumansACysteinyl leukotriene receptor antagonistHumansUfMet-Leu-Phe receptorantagonistHumansUProstaglandin D receptorunknownHumansUHeat shock protein HSP -alphaNot AvailableHumans",[],"['4-Quinolones', 'Anti-Allergic Agents', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Antiallergic Agents, Excl. Corticosteroids', 'Decongestants and Antiallergics', 'Decreased Histamine Release', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Mast Cell Stabilizers', 'Nasal Preparations', 'Ophthalmologicals', 'Quinolines', 'Quinolones', 'Respiratory Agents, Miscellaneous', 'Respiratory System Agents', 'Sensory Organs']" +DB00901,Bitolterol,Bitolterol mesylate was used to treat bronchospasms in asthma and COPD. It is a beta-2-adrenergic receptor agonist. Bitolterol was withdrawn from the market by Elan Pharmaceuticals in 2001.,['P07550'],"Bitolterol, an adrenergic bronchodilator, is a prodrug that widens constricted airways in the lungs by relaxing the smooth muscles that surround the bronchial passages. Bitolterol probably does not affect the inflammation in the lung, such as in bronchitis. Bitolterol is unique in that it is a prodrug because it must first be metabolized by the body before it becomes active.",CC1=CC=C(C=C1)C(=O)OC1=C(OC(=O)C2=CC=C(C)C=C2)C=C(C=C1)C(O)CNC(C)(C)C,Bitolterol is an adrenergic beta- agonist. Asthma results from a narrowing of the bronchial tubes. This narrowing is caused by muscle spasm and inflammation within the bronchial tubes. Agonism of the beta- adrenergic receptors by bitolterol leads to a relaxation of the smooth muscles surrounding these airway tubes which then increases the diameter and ease of air flow through the tubes.TargetActionsOrganismABeta- adrenergic receptorNot AvailableHumans,[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Drugs for Obstructive Airway Diseases', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists']" +DB00549,Zafirlukast,Zafirlukastis a leukotriene receptor antagonist used for prophylaxis and chronic treatment of asthma.,['Q9Y271'],"Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4than nonasthmatic subjects.In vitrostudies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs.",COC1=CC(=CC=C1CC1=CN(C)C2=C1C=C(NC(=O)OC1CCCC1)C=C2)C(=O)NS(=O)(=O)C1=CC=CC=C1C,"Zafirlukast is a selective and competitive receptor antagonist of leukotriene D and E (LTDand LTE), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.TargetActionsOrganismACysteinyl leukotriene receptor antagonistHumans",[],"['Acids, Acyclic', 'Agents to Treat Airway Disease', 'Amides', 'Anti-Asthmatic Agents', 'Carbamates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Heterocyclic Compounds, Fused-Ring', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Leukotriene Antagonists', 'Leukotriene Modifiers', 'NTCP Inhibitors', 'Respiratory System Agents', 'Sulfones', 'Sulfur Compounds']" +DB01364,Ephedrine,"Ephedrineis an alpha and beta-adrenergic agonist indicated to treat hypotension under anesthesia, allergic conditions, bronchial asthma, and nasal congestion.","['P35348', 'P08588', 'P07550', 'P23975']","Ephedrine increases blood pressure by stimulating heart rate and cardiac output and variably increasing peripheral resistance.9It causes bronchodilation due to the activation of beta-adrenergic receptors in the lungs. By stimulating alpha-adrenergic receptors in bladder smooth muscle cells, ephedrine also increases the resistance to the outflow of urine.8,9The therapeutic window of ephedrine is wide, as patients can be given doses of 5mg up to 50mg.11Patients should be counselled regarding the pressor effects of sympathomimetic amines and the risk of tachyphylaxis.4Also, the use of ephedrine for hypotension prophylaxis is associated with a higher risk of hypertension, compared to when ephedrine is used to treat hypotension.9",CN[C@@H](C)[C@H](O)C1=CC=CC=C1,"Ephedrine is a direct and indirect sympathomimetic amine.As a direct effect, ephedrine activates alpha-adrenergic and beta-adrenergic receptors. As an indirect effect, it inhibits norepinephrine reuptake and increases the release of norepinephrine from vesicles in nerve cells.These actions combined lead to larger quantities of norepinephrine present in the synapse for more extended periods of time, increasing stimulation of the sympathetic nervous system.Ephedrine acts as an agonist of alpha-, beta- and beta--adrenergic receptors. The stimulation of alpha--adrenergic receptors causes the constriction of veins and a rise in blood pressure, the stimulation of beta--adrenergic receptors increases cardiac chronotropy and inotropy, and the stimulation of beta--adrenergic receptors causes vasodilation and bronchodilation.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansUSodium-dependent noradrenaline transporterinverse agonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Alimentary Tract and Metabolism', 'Alpha-and Beta-adrenergic Agonists', 'Amines', 'Amino Alcohols', 'Antiobesity Preparations, Excl. Diet Products', 'Autonomic Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Centrally Acting Antiobesity Products', 'Cholinesterase substrates', 'Drugs for Obstructive Airway Diseases', 'Epinephrine and similars', 'Ethylamines', 'Herbs and Natural Products', 'Increased Norepinephrine Activity', 'Mydriatics and Cycloplegics', 'Nasal Preparations', 'Neurotransmitter Agents', 'Norepinephrine Releasing Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Propanolamines', 'Propanols', 'Sensory Organs', 'Sympathomimetic (Adrenergic) Agents', 'Sympathomimetics', 'Sympathomimetics Excl. Antiglaucoma Preparations', 'Sympathomimetics, Plain', 'Vasoconstrictor Agents']" +DB01366,Procaterol,Procaterolis a beta-2 adrenergic receptor agonist and bronchodilator used for the treatment of asthma and chronic obstructive pulmonary disease (COPD).,['P07550'],Procaterol is a long-acting beta-2-adrenergic receptor agonist. It is a potent bronchodilator that may be administered orally or by aerosol inhalation.,CC[C@@H](NC(C)C)[C@@H](O)C1=CC=C(O)C2=C1C=CC(=O)N2,"Beta()-receptor stimulation in the lung causes relaxation of bronchial smooth muscle, bronchodilation, and increased bronchial airflow.TargetActionsOrganismABeta- adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Heterocyclic Compounds, Fused-Ring', 'Hydroxyquinolines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Quinolines', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetics']" +DB00764,Mometasone,Mometasoneis a corticosteroid with no indications.,"['P04150', 'P06401']","Mometasone is a medium-potency synthetic corticosteroid with antiinflammatory, antipruritic, and vasoconstrictive properties. Studies in asthmatic patients have demonstrated that mometasone provides a favorable ratio of topical to systemic activity due to its primary local effect along with the extensive hepatic metabolism and the lack of active metabolites. Though effective for the treatment of asthma, glucocorticoids do not affect asthma symptoms immediately. Maximum improvement in symptoms following inhaled administration of mometasone furoate may not be achieved for 1 to 2 weeks or longer after starting treatment. When glucocorticoids are discontinued, asthma stability may persist for several days or longer. Mometasone has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone. The clinical significance of these findings is unknown.",[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Unbound corticosteroids cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Inflammation is decreased by diminishing the release of leukocytic acid hydrolases, prevention of macrophage accumulation at inflamed sites, interference with leukocyte adhesion to the capillary wall, reduction of capillary membrane permeability, reduction of complement components, inhibition of histamine and kinin release, and interference with the formation of scar tissue. The antiinflammatory actions of corticosteroids are thought to involve phospholipase Ainhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately times that of dexamethasone, times that of triamcinolone acetonide, times that of budesonide, and . times that of fluticasone.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUProgesterone receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Anti-Allergic Agents', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs for Obstructive Airway Diseases', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Nasal Preparations', 'Pregnadienediols', 'Pregnadienes', 'Pregnanes', 'Steroids', 'Thyroxine-binding globulin inhibitors']" +DB01408,Bambuterol,Bambuterolis a long acting beta2-adrenoceptor agonist for the management of lung diseases associated with bronchospasm.,"['P07550', 'P06276']","Bambuterol is a long acting beta2-adrenoceptor agonist used in the treatment of asthma. It is a prodrug of terbutaline. Bambuterol causes smooth muscle relaxation, resulting in dilation of bronchial passages.",CN(C)C(=O)OC1=CC(=CC(OC(=O)N(C)C)=C1)C(O)CNC(C)(C)C,"The pharmacologic effects of bambuterol are at least in part attributable to stimulation through beta-adrenergic receptors (beta receptors) of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic AMP. Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUCholinesteraseinhibitorHumans",[],"['Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cholinesterase Inhibitors', 'Cholinesterase substrates', 'Delayed-Action Preparations', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Long-acting beta-adrenoceptor agonists', 'Peripheral Nervous System Agents', 'Prodrugs', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists']" +DB00920,Ketotifen,Ketotifenis a histamine H1 receptor blocker and mast cell stabilizer used to treat mild atopic asthma and allergic conjunctivitis.,"['P35367', 'P52209']","Ketotifen is a non-competitive histamine antagonist and mast cell stabilizer.6Administered orally, it functions as a non-bronchodilator antiasthmatic drug by inhibiting the effects of endogenous substances known to be inflammatory mediators.7While effects can take 6 to 12 weeks to become apparent,5the use of ketotifen has been demonstrated to reduce the frequency, severity, and duration of asthma symptoms, and may allow for a reduction in the use of other asthma therapies.7",CN1CCC(CC1)=C1C2=C(SC=C2)C(=O)CC2=CC=CC=C12,"The precise mechanism(s) through which ketotifen exerts its therapeutic effects are unclear. Ketotifen is a potent and non-competitive antagonist of H histamine receptors, which is likely to be a significant contributor to its anti-allergic activity.In addition, ketotifen stabilizes mast cells and has demonstratedin vitrothe ability to inhibit the release of allergic and inflammatory mediators such as histamine, leukotrienes Cand D(i.e. SRS-A), and platelet-activating factor (PAF).Otherin vivoobservations thought to contribute to ketotifen's efficacy in asthma include the inhibition of various PAF-mediated processes (e.g. airway hyperreactivity, eosinophil and platelet accumulation in the airways), prevention of leukotriene-induced bronchoconstriction, and suppression of eosinophil priming.TargetActionsOrganismAHistamine H receptorantagonistHumansU-phosphogluconate dehydrogenase, decarboxylatinginhibitorHumans",[],"['Anti-Allergic Agents', 'Anti-Asthmatic Agents', 'Antihistamine Drugs', 'Antihistamines for Systemic Use', 'Antipruritics', 'Decongestants and Antiallergics', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Inhibitors', 'Ophthalmologicals', 'Other Antihistamines', 'Piperidines', 'Sensory Organs', 'Sulfur Compounds', 'Thiophenes', 'UGT1A3 substrates', 'UGT1A4 substrates']" +DB00983,Formoterol,Formoterolis an inhaled long-acting beta2-adrenergic receptor agonist used as a bronchodilator in the management of asthma and COPD.,"['P07550', 'P08588', 'P13945']","Formoterol works locally in the lungs as a bronchodilator, relaxing smooth muscle and opening up the airways. It possesses both a rapid onset of action (approximately 2-3 minutes)8and a long duration of action (up to 12 hours).16The use of long-acting beta-agonists (LABAs), such as formoterol, without concomitant inhaled corticosteroids in asthmatic patients should be avoided, as LABA monotherapy has been associated with an increased risk of asthma-related death.16",COC1=CC=C(CC(C)NCC(O)C2=CC(NC=O)=C(O)C=C2)C=C1,"Formoterol is a relatively selective long-acting agonist of beta-adrenergic receptors,,although it does carry some degree of activity at betaand betareceptors.Betareceptors are found predominantly in bronchial smooth muscle (with a relatively minor amount found in cardiac tissue) whereas betareceptors are the predominant adrenergic receptors found in the heart - for this reason, selectivity for betareceptors is desirable in the treatment of pulmonary diseases such as COPD and asthma.Formoterol has demonstrated an approximately -fold greater activity at betareceptors over betareceptors.On a molecular level, activation of beta receptors by agonists like formoterol stimulates intracellular adenylyl cyclase, an enzyme responsible for the conversion of ATP to cyclic AMP (cAMP). The increased levels of cAMP in bronchial smooth muscle tissue result in relaxation of these muscles and subsequent dilation of the airways, as well as inhibition of the release of hypersensitivity mediators (e.g. histamine, leukotrienes) from culprit cells, especially mast cells.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumans",['Maintenance therapy'],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Long-acting beta-adrenoceptor agonists', 'OCT1 inhibitors', 'OCT1 substrates', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB09273,Doxofylline,"Doxofyllineis a methylxanthine derivative used in chronic obstructive pulmonary disease, asthma, and bronchospasms.","['P07550', 'P29274', 'O00408']","Doxofylline is a methylxanthine bronchodilator with potent bronchodilator activity comparable to that of theophylline. In animal studies, doxofylline demonstrated to attenuate bronchoconstriction, inflammatory actions and the release of thromboxane A2 (TXA2) when challenged with platelet-activating factor9.Doxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. The affinity for adenosine A1, A2A and A2B receptors are reported to be all higher than 100 µM6. It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations7. A study demonstrated that doxofylline interacts with β2-adrenoceptors to induce blood vessel relaxation and airway smooth muscle relaxation. In dog studies, doxofylline decreased airway responsiveness at a dose that did not affect heart rate and respiratory rate6.",CN1C2=C(N(CC3OCCO3)C=N2)C(=O)N(C)C1=O,"The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation.The interaction of doxofylline with beta- adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking. Serine and serine residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed. Via mediating the actions of beta- adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation.There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study. It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro.Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)- secretion in ASM cells.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUAdenosine receptor AaantagonistHumansAcGMP-dependent ','-cyclic phosphodiesteraseinhibitorHumans",[],"['Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alkaloids', 'Anti-Asthmatic Agents', 'Antitussive Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Central Nervous System Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Peripheral Nervous System Agents', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Purines', 'Purinones', 'Respiratory System Agents', 'Vasodilating Agents', 'Xanthine derivatives']" +DB00180,Flunisolide,Flunisolideis an inhaled corticosteroid used as a prophylactic therapy in the maintenance treatment of asthma.,['P04150'],"Flunisolide is a synthetic corticosteroid. It is administered either as an oral metered-dose inhaler for the treatment of asthma or as a nasal spray for treating allergic rhinitis. Corticosteroids are naturally occurring hormones that prevent or suppress inflammation and immune responses. When given as an intranasal spray, flunisolide reduces watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, sneezing, and itching oat the back of the throat that are common allergic symptoms.",[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)CO,"Flunisolide is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flunisolide binds to plasma transcortin, and it becomes active when it is not bound to transcortin.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Adrenals', 'Agents to Treat Airway Disease', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Fused-Ring Compounds', 'Immunosuppressive Agents', 'Nasal Preparations', 'Pregnadienes', 'Pregnanes', 'Respiratory System Agents', 'Steroids', 'Steroids, Fluorinated']" +DB00874,Guaifenesin,"Guaifenesinis an expectorant commonly found in OTC products for the symptomatic relief from congested chests and coughs associated with cold, bronchitis, and/or other breathing illnesses.","['Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391']","Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material9. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent9. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway9.",COC1=CC=CC=C1OCC(O)CO,"Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion. Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture. Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual.Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist.TargetActionsOrganismUNMDA receptorantagonistHumans","['Airway secretion clearance therapy', 'Expectorant']","['Benzene Derivatives', 'Catechols', 'Cough and Cold Preparations', 'Ethers', 'Expectorants', 'Methyl Ethers', 'Phenols', 'Phenyl Ethers', 'Respiratory System Agents']" +DB04576,Fleroxacin,Fleroxacin is a broad-spectrum antimicrobial fluoroquinolone. It strongly inhibits the DNA-supercoiling activity of DNA gyrase. Fleroxacin is not an inhibitor of CYP1A2.1,"['P43700', 'P43702', 'P11388']",Fleroxacin is a broad-spectrum antimicrobial fluoroquinolone. It strongly inhibits the DNA-supercoiling activity of DNA gyrase.,CN1CCN(CC1)C1=C(F)C=C2C(=O)C(=CN(CCF)C2=C1F)C(O)=O,"The inhibition of DNA gyrase and DNA topoisomerase leads ultimately to cell death as these enzymes are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase -alphainhibitorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Antineoplastic Agents', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01656,Roflumilast,Roflumilastis a selective phosphodiesterase-4 inhibitor indicated to decrease the risk of exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) and to treat plaque psoriasis.,"['P27815', 'Q07343', 'Q08493', 'Q08499']","Roflumilast and its active metabolite, roflumilast N-oxide, increase cyclic adenosine-3′, 5′-monophosphate (cAMP) in affected cells by inhibiting PDE4. They are highly selective for PDE4 and are effectively inactive against PDEs 1, 2, 3, 5, and 7.7",FC(F)OC1=C(OCC2CC2)C=C(C=C1)C(=O)NC1=C(Cl)C=NC=C1Cl,"Roflumilast and its active metabolite (roflumilast N-oxide) are inhibitors of PDE. Roflumilast and roflumilast N-oxide inhibition of PDE (a major cyclic ′,′-adenosine monophosphate (cyclic AMP) metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP. The specific mechanism(s) by which roflumilast exerts its therapeutic action is not well defined.TargetActionsOrganismAcAMP-specific ','-cyclic phosphodiesterase (PDE)inhibitorHumans",[],"['Acids, Carbocyclic', 'Agents to Treat Airway Disease', 'Amides', 'Amines', 'Benzene Derivatives', 'Benzoates', 'Cycloparaffins', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Phosphodiesterase 4 Inhibitors', 'Phosphodiesterase Inhibitors', 'Pyridines']" +DB01288,Fenoterol,Fenoterolis a beta-2 adrenergic agonist and bronchodilator used for the symptomatic treatment of asthma.,"['P07550', 'P08588', 'P13945']",Fenoterol is a beta agonist designed to open up the airways to the lungs by decreasing bronchconstriction.,CC(CC1=CC=C(O)C=C1)NCC(O)C1=CC(O)=CC(O)=C1,"Beta()-receptor stimulation in the lung causes relaxation of bronchial smooth muscle, bronchodilation, and increased bronchial airflow.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Anticholinergic Agents', 'Autonomic Agents', 'Benzene Derivatives', 'Bronchodilator Agents', 'Catechols', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Genito Urinary System and Sex Hormones', 'Metaproterenol', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenols', 'Reproductive Control Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetics', 'Sympathomimetics, Labour Repressants', 'Tocolytic Agents']" +DB00909,Zonisamide,Zonisamideis a sulfonamide anticonvulsant used to treat partial seizures.,"['P35498', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q15858', 'Q9UI33', 'Q07699', 'O60939', 'Q9NY72', 'Q8IWT1', 'O43497', 'O95180', 'Q9P0X4', 'P00915', 'P00918', 'P07451', 'P22748', 'P35218', 'Q9Y2D0', 'P23280', 'P43166', 'P35219', 'Q16790', 'Q9NS85', 'O75493', 'O43570', 'Q8N1Q1', 'Q9ULX7', 'P27338', 'P21397', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","By stopping the spread of seizure discharges, zonisamide prevents the extensor component of tonic convulsion, restricts the spread of focal seizures and prevents the propagation of seizures from the cortex to subcortical structures.4,5In animal models, zonisamide was effective against tonic extension seizures but ineffective against clonic seizures. It also increased the threshold for generalized seizures and reduced the duration of cortical focal seizures.7Aside from its antiepileptic effects, zonisamide is capable of activating neuroprotective mechanisms. It inhibits nitric oxide synthase and ​​reduces ischemia-induced memory impairment and lipid peroxidation.4The use of zonisamide may lead to potentially fatal reactions. Severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, and aplastic anemia have been reported in patients treated with sulfonamides such as zonisamide. Zonisamide may also lead to the development of serious hematological events, drug reaction with eosinophilia and systemic symptoms (DRESS) and multi-organ hypersensitivity, acute myopia and secondary angle closure glaucoma, as well as suicidal behaviour and ideation.7,8Zonisamide is a carbonic anhydrase inhibitor, which may lead to metabolic acidosis in patients treated with this drug. Its therapeutic effects due to this pharmacological action are unknown.7",NS(=O)(=O)CC1=NOC2=CC=CC=C12,"The mechanism of action by which zonisamide controls seizures has not been fully established. However, its antiepileptic properties may be due to its effects on sodium and calcium channels.,Zonisamide blocks sodium channels and reduces voltage-dependent, transient inward currents, stabilizing neuronal membranes and suppressing neuronal hypersynchronization.,It affects T-type calcium currents, but has no effect on L-type calcium currents.,,Zonisamide suppresses synaptically-driven electrical activity by altering the synthesis, release, and degradation of neurotransmitters, such as glutamate, gamma-aminobutyric acid (GABA), dopamine, serotonin (-hydroxytryptamine-HT), and acetylcholine.,Furthermore, it binds to the GABA/benzodiazepine receptor ionophore complex without producing changes in chloride flux.,In vitrostudies have suggested that zonisamide does not affect postsynaptic GABA or glutamate responses, nor the neuronal or glial uptake of [H]-GABA.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansASodium channel subunit beta-inhibitorHumansASodium channel subunit beta-inhibitorHumansASodium channel subunit beta-inhibitorHumansASodium channel subunit beta-inhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansAVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase A, mitochondrialinhibitorHumansUCarbonic anhydrase B, mitochondrialinhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase-related proteininhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase-related protein inhibitorHumansUCarbonic anhydrase-related protein inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUAmine oxidase [flavin-containing] BinhibitorHumansUAmine oxidase [flavin-containing] AinhibitorHumansUGABA(A) Receptor Benzodiazepine Binding SitebinderHumans",[],"['Agents causing hyperkalemia', 'Amides', 'Anti-epileptic Agent', 'Antiarrhythmic agents', 'Anticonvulsants', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Carbonic Anhydrase Inhibitors', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Diuretics', 'Drugs that are Mainly Renally Excreted', 'Isoxazoles', 'Membrane Transport Modulators', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Nervous System', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'UGT1A1 Substrates']" +DB03575,Phencyclidine,"A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-D-aspartate). As a drug of abuse, it is known as PCP and Angel Dust.","['Q8TCU5', 'Q99720']","Phencyclidine works primarily as an NMDA receptor antagonist, which blocks the activity of the NMDA Receptor.",C1CCN(CC1)C1(CCCCC1)C1=CC=CC=C1,"The N-methyl-D-Aspartate (NMDA) receptor, a type of ionotropic receptor, is found on the dendrites of neurons and receives signals in the form of neurotransmitters. It is a major excitatory receptor in the brain. Normal physiological function requires that the activated receptor fluxes positive ions through the channel part of the receptor. PCP enters the ion channel from the outside of the neuron and binds, reversibly, to a site in the channel pore, blocking the flux of positive ions into the cell. PCP therefore inhibits depolarization of neurons and interferes with cognitive and other functions of the nervous system.TargetActionsOrganismAGlutamate receptor ionotropic, NMDA AantagonistHumansUSigma non-opioid intracellular receptor Not AvailableHumans",[],"['Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Excitatory Amino Acid Agents', 'Excitatory Amino Acid Antagonists', 'Hallucinogens', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'Phencyclidine, antagonists & inhibitors', 'Piperidines', 'Psychotropic Drugs']" +DB01185,Fluoxymesterone,"Fluoxymesteroneis a synthetic androgenic anabolic steroid that used in the treatment of hypogonadism and delayed puberty in males, as well as breast neoplasms in women.","['P10275', 'P03372', 'P04150', 'P80365']","Fluoxymesterone is a synthetic androgen, or male hormone, similar to testosterone. Fluoxymesterone works by attaching itself to androgen receptors; this causes it to interact with the parts of the cell involved in the making of proteins. It may cause an increase in the synthesis of some proteins or a decrease in the synthesis of others. These proteins have a variety of effects, including blocking the growth of some types of breast cancer cells, stimulating cells that cause male sexual characteristics, and stimulating the production of red blood cells.",[H][C@@]12CC[C@](C)(O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"Fluoxymesterone is a synthetic androgenic anabolic steroid and is approximately times as potent as natural methyltestosterone. Like testosterone and other androgenic hormones, fluoxymesterone binds to the androgen receptor. It produces retention of nitrogen, sodium, potassium, and phosphorus; increases protein anabolism; decreases amino acid catabolism and decreased urinary excretion of calcium. The antitumour activity of fluoxymesterone appears related to reduction or competitive inhibition of prolactin receptors or estrogen receptors or production.TargetActionsOrganismAAndrogen receptoragonistHumansAEstrogen receptor alphaantagonistHumansUGlucocorticoid receptorantagonistHumansUCorticosteroid -beta-dehydrogenase isozyme inhibitorHumans",[],"['3-Oxoandrosten (4) Derivatives', 'Anabolic Agents', 'Androgens', 'Androstanes', 'Androstenediols', 'Androstenes', 'Androstenols', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Steroids, Fluorinated']" +DB01520,Tenocyclidine,"Tenocyclidine (TCP, thienyl cyclohexylpiperidine) is a dissociative anesthetic drug with stimulant and hallucinogenic effects. It is more potent than phencyclidine and hence, this drug was classified under the schedule 1 in 1970.","['Q8TCU5', 'O60391', 'Q12879', 'Q14957', 'Q13224', 'Q693P7', 'O15399']","When compared to phencyclidine, tenocyclidine presents more affinity for NMDA receptors and less affinity for sigma receptors.",C1CCN(CC1)C1(CCCCC1)C1=CC=CS1,"The primary interactions are as a non-competitive antagonist at the A-subunit of the NMDAR in Homo sapiens. TCP is known to bind, with relatively high affinity, to the D subunit of the human DAT, in addition to displaying a positive antagonistic effect at the α-subunit of the Nicotinic Acetylcholine Receptor (nAChR). It also binds to the mu-opioid receptor, which seems to be a central part of the mechanism of action of drugs in this class. (For example, Dizocilpine [MK-] shows little appreciable analgesic effect despite having a high specificity for the NMDA-A and NMDA-B subunits - this may well be mediated by the lack of related efficacy at the mu-opioid receptor, though the NMDAR certainly does play a role in transmission of pain signals).TargetActionsOrganismAGlutamate receptor ionotropic, NMDA AantagonistHumansAGlutamate receptor ionotropic, NMDA BantagonistHumansAGlutamate receptor ionotropic, NMDA AantagonistHumansAGlutamate receptor ionotropic, NMDA CantagonistHumansAGlutamate receptor ionotropic, NMDA BantagonistHumansUAlpha- nicotinic cholinergic receptor subunitantagonistHumansUGlutamate receptor ionotropic, NMDA DantagonistHumans",[],"['Central Nervous System Agents', 'Compounds used in a research, industrial, or household setting', 'Illicit Drugs', 'Neuroprotective Agents', 'NMDA Receptor Antagonists', 'Piperidines', 'Protective Agents', 'Street Drugs']" +DB00967,Desloratadine,"Desloratadineis a second generation tricyclic antihistamine used to treat seasonal and non seasonal allergic rhinitis, pruritus, and urticaria.",['P35367'],"Desloratadine is a long-acting second-generation H1-receptor antagonist which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be ""activated,"" releasing other chemicals which produce the effects that we associate with allergies. Desloratadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Desloratadine does not enter the brain from the blood and, therefore, does not cause drowsiness.",ClC1=CC2=C(C=C1)C(=C1CCNCC1)C1=C(CC2)C=CC=N1,"Like other H-blockers, Desloratadine competes with free histamine for binding at H-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",['Antihistamine'],"['Anticholinergic Agents', 'Antihistamines for Systemic Use', 'Benzocycloheptenes', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Dibenzocycloheptenes', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Loratadine and derivatives', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Piperidines', 'QTc Prolonging Agents']" +DB01497,Etorphine,"A narcotic analgesic morphinan used as a sedative in veterinary practice. In certain countries, etorphine is classified as a Schedule 1 drug and hence, in these countries, it can be used legally only by health professionals and for research purposes. Etorphine is only available to the patients under an official prescription. In the US, Etorphine is listed as a Schedule I drug, although Etorphine hydrochloride is classified as Schedule II.","['P35372', 'P41143', 'P41145', 'P41146', 'O60858', 'P01189']","Etorphine is a synthetic cousin of morphine and 40,000 times more powerful.",[H][C@]12CC3=C4C(OC5[C@@]4(CCN1C)[C@]21CC(C(C)(O)CCC)C5(OC)C=C1)=C(O)C=C3,"Etorphine is an agonist at mu, delta, and kappa opioid receptors. It also has a weak affinity for the ORL nociceptin/orphanin FQ receptor.TargetActionsOrganismAMu-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansAKappa-type opioid receptoragonistHumansUNociceptin receptoragonistHumansUE ubiquitin-protein ligase TRIMagonistHumansUPro-opiomelanocortinNot AvailableHumans",[],"['Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Narcotics', 'Opiate Alkaloids', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00341,Cetirizine,Cetirizineis a selective Histamine-1 antagonist drug used in allergic rhinitis and chronic urticaria.,['P35367'],"General effects and respiratory effectsCetirizine, the active metabolite of the piperazine H1-receptor antagonist hydroxyzine, minimizes or eliminates the symptoms of chronic idiopathic urticaria, perennial allergic rhinitis, seasonal allergic rhinitis, allergic asthma, physical urticaria, and atopic dermatitis. +The clinical efficacy of cetirizine for allergic respiratory diseases has been well established in numerous trialsLabel.Effects on urticaria/anti-inflammatory effectsIt has anti-inflammatory properties that may play a role in asthma management1. There is evidence that cetirizine improves symptoms of urticaria. Marked clinical inhibition of a wheal and flare response occurs in infants, children as well as adults within 20 minutes of one oral dose and lasts for 24 h1. Concomitant use of cetirizine reduces the duration and dose of topical anti-inflammatory formulas used for the treatment of atopic dermatitis1.",OC(=O)COCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1,"Cetirizine, a metabolite ofhydroxyzine, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models.In vivoandex vivoanimal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain.Ex vivostudies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H receptors significantlyLabel.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Central Nervous System Depressants', 'Decongestants and Antiallergics', 'Drugs that are Mainly Renally Excreted', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Ophthalmologicals', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Piperazine Derivatives', 'Piperazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sensory Organs']" +DB00134,Methionine,Methionineis an amino acid commonly found as a component in total parenteral nutrition.,"['Q9UBK8', 'Q99707', 'P50579', 'Q93088', 'Q9H2M3']","L-Methionine is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity.",CSCC[C@H](N)C(O)=O,"The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.TargetActionsOrganismUMethionine synthase reductaseproduct ofHumansUMethionine synthaseproduct ofHumansUMethionine aminopeptidase product ofHumansUBetaine--homocysteine S-methyltransferase product ofHumansUS-methylmethionine--homocysteine S-methyltransferase BHMTproduct ofHumans",['Amino acid supplementation'],"['Amino Acids', 'Amino Acids, Essential', 'Amino Acids, Neutral', 'Amino Acids, Peptides, and Proteins', 'Amino Acids, Sulfur', 'Antidotes', 'Dietary Supplements', 'Proteinogenic Amino Acids', 'Sulfur Compounds', 'Supplements']" +DB00979,Cyclopentolate,Cyclopentolateis an anticholinergic used to cause mydriasis and cycloplegia for diagnostic testing.,['P11229'],"Cyclopentolate is an anti-muscarinic in the same class as atropine and scopolamine. Cyclopentolate blocks the receptors in the muscles of the eye (muscarinic receptors). These receptors are involved controlling the pupil size and the shape of the lens. Cyclopentolate thus induces relaxation of the sphincter of the iris and the ciliary muscles. When applied topically to the eyes, it causes a rapid, intense cycloplegic and mydriatic effect that is maximal in 15 to 60 minutes; recovery usually occurs within 24 hours. The cycloplegic and mydriatic effects are slower in onset and longer in duration in patients who have dark pigmented irises.",CN(C)CCOC(=O)C(C1=CC=CC=C1)C1(O)CCCC1,"By blocking muscarinic receptors, cyclopentolate produces dilatation of the pupil (mydriasis) and prevents the eye from accommodating for near vision (cycloplegia).TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Acids, Carbocyclic', 'Anticholinergic Agents', 'Autonomic Agents', 'Cholinergic Agents', 'Cholinesterase substrates', 'Muscarinic Antagonists', 'Mydriatics', 'Mydriatics and Cycloplegics', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Phenylacetates', 'Sensory Organs']" +DB00555,Lamotrigine,Lamotrigineis a phenyltriazine antiepileptic used to treat some types of epilepsy and bipolar I disorder.,"['Q15878', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'P30542', 'P29274', 'P35348', 'P08913', 'P08588', 'P21728', 'P21918', 'P14416', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928', 'P35367', 'P41145', 'P02708', 'P28223', 'P46098', 'P42261']","Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity.10,14A note on cardiovascular effectsThe metabolite of lamotrigine, 2-N-methyl metabolite (formed by glucuronidation), is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and at higher doses, complete AV block. Although this harmful metabolite is only found in trace amounts in humans, plasma concentrations may increase in conditions that cause decreased drug glucuronidation, such as liver disease.7,14,15",NC1=NC(N)=C(N=N1)C1=C(Cl)C(Cl)=CC=C1,"The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters.,,Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states.Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin -HT receptor. Lamotrigine also weakly binds to Adenosine A/A receptors, α/α/β adrenergic receptors, dopamine D/D receptors, GABA A/B receptors, histamine H receptors, κ-opioid receptor (KOR), mACh receptors and serotonin -HT receptors with an IC> µM. Weak inhibitory effects were observed at sigma opioid receptors.An in vivo study revealed evidence that lamotrigine inhibits Cav. (R-type) calcium currents, which may also contribute to its anticonvulsant effects.TargetActionsOrganismAVoltage-dependent R-type calcium channel subunit alpha-E (CACNAE)inhibitorHumansAVoltage-gated sodium channel alpha subunitinhibitorHumansUAdenosine receptor AinhibitorHumansUAdenosine receptor AainhibitorHumansUAlpha-A adrenergic receptorinhibitorHumansUAlpha-A adrenergic receptorinhibitorHumansUBeta- adrenergic receptorinhibitorHumansUD() dopamine receptorinhibitorHumansUDopamine D receptoragonistinhibitorHumansUGABA(A) ReceptorantagonistinducerHumansUGABA(A) Receptor Benzodiazepine Binding SiteinhibitorHumansUHistamine H receptorantagonistHumansUKappa-type opioid receptorinhibitorHumansUAcetylcholine receptor subunit alphainhibitorHumansU-hydroxytryptamine receptor AinhibitorHumansU-hydroxytryptamine receptor AinhibitorHumansUGlutamate receptor inhibitorHumans",['Conversion to monotherapy'],"['Agents causing hyperkalemia', 'Agents producing tachycardia', 'Anti-epileptic Agent', 'Antiarrhythmic agents', 'Anticholinergic Agents', 'Anticonvulsants', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Membrane Transport Modulators', 'Miscellaneous Anticonvulsants', 'Mood Stabilizer', 'Muscarinic Antagonists', 'Nervous System', 'OCT1 substrates', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Sodium Channel Blockers', 'Tranquilizing Agents', 'Triazines', 'UGT1A1 Inducers', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A4 substrates']" +DB00577,Valaciclovir,Valacicloviris an guanine nucleoside antiviral used to treat herpes exacerbations.,"['Q9QNF7', 'P04293']","Antiviral effectsValacyclovir shows varying levels of inhibition towards herpes simplex virus types 1 (HSV-1), 2 (HSV-2), Varicella Zoster Virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The quantitative relationship between the cell culture susceptibility of herpesviruses to antivirals and the clinical response of humans to the same antiviral therapy has not yet been elucidated. Sensitivity testing results, described by the concentration of drug needed to inhibit the growth of the virus by 50% in cell culture (EC50), vary widely depending on various factorsLabel.Clinical study resultsFor the various conditions below, clinical study results are summarized as followsLabel:Cold soresImmunocompetent volunteers with cold sores were observed following the administration of a 1-day regimen (2 grams of valacyclovir twice a day for 1 day followed by one day of placebo) or a 2-day regimen (2 grams of valacyclovir twice daily for two days). The average duration of cold sore episodes was approximately 1 day shorter in treated subjects when compared to subjects treated with placebo. A 2-day drug administration regimen of valacyclovir did not provide superior benefit over the 1-day regimen. There was no clinically significant difference observed between subjects receiving valacyclovir or placebo in the prevention of progression of cold sore lesions after the papular stage, indicating that timing of valacyclovir administration is an important considerationLabel.Initial genital herpes episodes643 immunocompetent adults with first-episode genital herpes who presented within 72 hours of symptom onset were randomized in a double-blind trial to receive 10 days of valacyclovir 1 gram twice daily (n = 323) or oral acyclovir 200 mg 5 times a day (n = 320). In both groups, the median time to healing of herpetic lesions was measured to be 9 days, and the median time to cessation of pain was found to be 5 days, with the median time to cessation of viral shedding was approximately 3 days.Recurrent genital herpes episodesThe results of 3 separate studies of patients taking 3 to 5-day regimens of valacyclovir showed an average of 4 days to lesion healing, 2-3 days to resolution of pain associated with the lesions, with an average of 2 days until the cessation of viral sheddingLabel. These findings showed valacyclovir administration to show superior beneficial effects when compared to the findings associated with placebo administration.A note on resistanceThe resistance of Herpes Simplex Virus and Varicella Zoster Virus to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of VZV with decreased susceptibility to acyclovir have been isolated from patients diagnosed with AIDS. A total of 522 TK-deficient mutants of VZV have been identified in these casesLabel.",CC(C)[C@H](N)C(=O)OCCOCN1C=NC2=C1NC(N)=NC2=O,"Valacyclovir is the L-valine ester of aciclovir. It is classified as a nucleoside analog DNA polymerase enzyme inhibitor. Aciclovir is a purine (guanine) nucleoside analog is a metabolite that heavily contributes to the pharmacological actions of valacyclovir. In fact, most of valacyclovir's activity is attributed to acyclovir.Valacyclovir is rapidly and almost completely converted in man to aciclovir and valine, likely by the enzymevalacyclovir hydrolase. +Aciclovir is a selective inhibitor of the herpes viruses, possessing in vitro activity against herpes simplex viruses (HSV) type and type , varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr Virus (EBV), as well as human herpesvirus (HHV-). Aciclovir has been shown to inhibit herpes virus DNA synthesis after it has been phosphorylated to the active triphosphate form.The first stage of drug phosphorylation for acyclovir requires activation by a virus-specific enzyme. In the case of HSV, VZV and EBV this enzyme is the viralthymidine kinase(TK), which is only found in virus-infected cells. The process of phosphorylation is completed (conversion from mono- to triphosphate) by cellular kinases. Acyclovir triphosphate competitively inhibits the virus DNA polymerase and incorporation of this agent results in DNA chain termination, stopping virus DNA synthesis and blocking virus replication. The inhibitory capabilities of acyclovir are highly selective due to the drug's strong affinity forthymidine kinase(TK)Label.In summary, the antiviral effects of valacyclovir are achieved in waysLabel:) competitive inhibition of viral DNA polymerase) incorporation and termination of the growing viral DNA chain) inactivation of the viral DNA polymerase. The higher level of antiviral activity of acyclovir against HSV compared with VZV is attributed to its more efficient phosphorylation by viral thymidine kinase (TK).TargetActionsOrganismAThymidine kinasesubstrateHHV-ADNA polymerase catalytic subunitinhibitorHHV-",['Suppression of Recurrent Genital Herpes (RGH)'],"['Acyclovir and prodrug', 'Amino Acids', 'Amino Acids, Branched-Chain', 'Amino Acids, Peptides, and Proteins', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor', 'Herpes Zoster Virus Nucleoside Analog DNA Polymerase Inhibitor', 'Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'Nephrotoxic agents', 'Nucleic Acid Synthesis Inhibitors', 'Nucleosides and Nucleotides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'OAT3/SLC22A8 Substrates', 'Prodrugs', 'Purines', 'Purinones']" +DB00263,Sulfisoxazole,Sulfisoxazoleis a sulfonamide antibiotic used with other antibiotics to prevent and treat a variety of bacterial infections.,['P0AC13'],"Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors ofp-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.",CC1=NOC(NS(=O)(=O)C2=CC=C(N)C=C2)=C1C,"Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.TargetActionsOrganismADihydropteroate synthaseinhibitorEscherichia coli (strain K)",[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Moderate Risk QTc-Prolonging Agents', 'Ophthalmologicals', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Sensory Organs', 'Short-Acting Antibacterial Sulfonamides', 'Sulfanilamides', 'Sulfonamide Antibacterial', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds']" +DB00677,Isoflurophate,"An irreversible cholinesterase inhibitor with actions similar to those of echothiophate. It is a powerful miotic used mainly in the treatment of glaucoma. Its vapor is highly toxic and it is recommended that only solutions in arachis oil be used therapeutically. (From Martindale, The Extra Pharmacopoeia, 29th ed, p1330)","['P22303', 'P06276', 'P02787']","Isoflurophate is used as ocular drops in the treatment of chronic glaucoma. Isoflurophate is an organophosphorus compound that acts as an irreversible cholinesterase inhibitor. As such, it displays parasympathomimetic effects. Isoflurophate is used in the eye to treat certain types of glaucoma and other eye conditions, such as accommodative esotropia. They may also be used in the diagnosis of certain eye conditions, such as accommodative esotropia. Isoflurophate damages the acetylcholinesterase enzyme and is therefore irreversible, however, pralidoxime can displace organophosphates such as isoflurophate from acetylcholinesterase, but only if administered before isoflurophate damages (alkylates) the enzyme.",CC(C)OP(F)(=O)OC(C)C,The mechanism of isoflurophate's action involves the irreversible inhibition of cholinesterase.TargetActionsOrganismAAcetylcholinesteraseinhibitorHumansACholinesteraseinhibitorHumansUSerotransferrinNot AvailableHumans,[],"['Cholinergic Agents', 'Cholinesterase Inhibitors', 'Enzyme Inhibitors', 'Neurotransmitter Agents', 'Ophthalmics', 'Organofluorophosphonates', 'Organophosphonates', 'Organophosphorus Compounds', 'Protease Inhibitors']" +DB06283,Ziconotide,"Ziconotideis an N-type calcium channel antagonist used to manage patients with severe chronic pain who cannot tolerate, or who have not responded adequately to other treatments such as intrathecal morphine and systemic analgesics.","['Q00975', 'O00555']","Ziconotide inhibits N-type calcium channels involved in nociceptive signalling, primarily in the dorsal horn of the spinal cord.5,7,8,9,12,14,18Although binding is reversible, careful dosing is required to ensure therapeutic effects while minimizing adverse effects, and ziconotide has been described as possessing a narrow therapeutic window.13,18Patients taking ziconontide may experience cognitive and neuropsychiatric symptoms, reduced levels of consciousness, and elevated serum creatine kinase levels. In addition, ziconotide may increase the risk of infection, including serious cases of meningitis. Patients who withdraw from opiates for ziconotide initiation are advised to taper off the dose.18",[H][C@]12CSSC[C@]3([H])NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CSSC[C@]([H])(NC(=O)[C@]([H])(CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC1=O)C(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC3=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N2,"Nociceptive pain signalling is a complex processing pathway involving peripheral nociceptors, primary afferent nerve fibres, and downstream CNS neurons located in the spinal cord.,Voltage-gated calcium channels (VGCCs) are important regulatory components of neural signalling and include the N-type (Cav.) heteromultimeric high-voltage type calcium channels.Chronic pain conditions, including inflammatory and neuropathic pain, often involve the aberrant upregulation of VGCC activity through various cellular mechanisms, which can lead to allodynia and hyperalgesia.Specifically, N-type channel activation in lightly myelinated Aδ- and C-fibres is known to mediate the release of neurotransmitters substance P (SP), calcitonin gene-related peptide (CGRP), and glutamate, which influence downstream neural activation and pain perception.,,,,In addition, SP and CGRP induce inflammation, potentially exacerbating pre-existing inflammatory chronic pain.Ziconotide belongs to the ω-conotoxin class of neurotoxic peptides derived from the cone snailConus maguswhich are capable of inhibiting N-type VGCCs.,,,,Although the exact mechanism is yet to be elucidated, it is thought that ω-conotoxins function through direct occlusion of the ion pore to prevent calcium translocation across the membrane.Additional studies involving expression of chimeric subunits and molecular modelling suggest that insertion of the ziconotide Metresidue into a hydrophobic pocket formed by Ile, Phe, and Leuof Cav. increases binding and may be associated with toxic adverse effects.TargetActionsOrganismAVoltage-dependent N-type calcium channel subunit alpha-BinhibitorHumansNVoltage-dependent P/Q-type calcium channel subunit alpha-AinhibitorHumans",[],"['Analgesics', 'Analgesics, Non-Narcotic', 'Antiarrhythmic agents', 'Calcium Channel Blockers', 'Calcium Channels, N-Type', 'Calcium-Regulating Hormones and Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Complex Mixtures', 'Compounds used in a research, industrial, or household setting', 'Conotoxins', 'Fluids and Secretions', 'Marine Toxins', 'Membrane Transport Modulators', 'Mollusk Venoms', 'N-Calcium Channel Receptor Antagonists', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neuroprotective Agents', 'Peripheral Nervous System Agents', 'Protective Agents', 'Sensory System Agents', 'Toxins, Biological', 'Vasodilating Agents', 'Venoms']" +DB00387,Procyclidine,Procyclidineis an antispasmodic drug used to treat parkinsonism of various types and in the treatment of extrapyramidal symptoms.,"['P20309', 'P11229', 'P08172', 'P08173']","Procyclidine has an atropine-like action on parasympathetic-innervated peripheral structures including smooth muscle. It's antispasmodic effects are thought to be related to the blockage of central cholinergic receptors M1, M2 and M4. It is used to treat symptomatic Parkinsonism and extrapyramidal dysfunction caused by antipsychotic agents.",OC(CCN1CCCC1)(C1CCCCC1)C1=CC=CC=C1,"The mechanism of action is unknown. It is thought that Procyclidine acts by blocking central cholinergic receptors, and thus balancing cholinergic and dopaminergic activity in the basal ganglia. Many of its effects are due to its pharmacologic similarities with atropine. Procyclidine exerts an antispasmodic effect on smooth muscle, and may produce mydriasis and reduction in salivation.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Central Nervous System Agents', 'Cholinergic Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Pyrrolidines', 'Tertiary Amines']" +DB00906,Tiagabine,Tiagabineis an antiepileptic used to treat partial seizures.,['P30531'],"Tiagabine is used primarily as an anticonvulsant for the adjunctive treatment of epilepsy. The precise mechanism by which Tiagabine exerts its antiseizure effect is unknown, although it is believed to be related to its ability to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Tiagabine binds to recognition sites associated with the GABA uptake carrier. It is thought that, by this action, Tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells.",CC1=C(SC=C1)C(=CCCN1CCC[C@H](C1)C(O)=O)C1=C(C)C=CS1,"Though the exact mechanism by which Tiagabine exerts its effect on the human body is unknown, it does appear to operate as a selective GABA reuptake inhibitor.TargetActionsOrganismASodium- and chloride-dependent GABA transporter inhibitorHumans",[],"['Anti-epileptic Agent', 'Anticonvulsants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Fatty Acid Derivatives', 'GABA Agents', 'GABA Uptake Inhibitors', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Nipecotic Acid and Derivatives', 'Piperidines', 'UGT1A1 Substrates']" +DB00376,Trihexyphenidyl,Trihexyphenidylis an antispasmodic drug used as an adjunct drug in the management of parkinsonism and as a treatment for extrapyramidal symptoms caused by drugs affecting the central nervous system (CNS).,"['P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Trihexyphenidyl is an antimuscarinic indicated as an adjunct in the treatment of parkinsonism or as a treatment for drug-induced extrapyramidal symptoms.11,12It has a long duration of action as it does not need to be given every day.13It has a wide therapeutic window, with acute toxicity being non fatal in doses as high as 300 mg.13Patients should have their iridocorneal angle examined before and intraocular pressure monitored during therapy.13Patients should be counselled regarding the risk of anhidrosis and hyperthermia.13",OC(CCN1CCCCC1)(C1CCCCC1)C1=CC=CC=C1,"Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M subtype.In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally.,Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum.Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.,TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Central Nervous System Agents', 'Cholinergic Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Piperidines', 'Tertiary Amines']" +DB04844,Tetrabenazine,Tetrabenazineis a vesicular monoamine transporter 2 (VMAT) inhibitor used for the management of chorea associated with Huntington's Disease.,"['Q05940', 'P14416']","Prolongation of the QTc interval has been observed at doses of 50 mg. In rats, it has been observed that tetrabenazine or its metabolites bind to melanin-containing tissues such as the eyes and skin. After a single oral dose of radiolabeled tetrabenazine, radioactivity was still detected in eye and fur at 21 days post dosing.",COC1=C(OC)C=C2C3CC(=O)C(CC(C)C)CN3CCC2=C1,"Tetrabenazine is a reversible human vesicular monoamine transporter type inhibitor (Ki = nM). It acts within the basal ganglia and promotes depletion of monoamine neurotransmitters serotonin, norepinephrine, and dopamine from stores. It also decreases uptake into synaptic vesicles. Dopamine is required for fine motor movement, so the inhibition of its transmission is efficacious for hyperkinetic movement. Tetrabenazine exhibits weak in vitro binding affinity at the dopamine D receptor (Ki = nM).TargetActionsOrganismASynaptic vesicular amine transporterinhibitorHumansUDopamine D receptorinhibitorHumans",[],"['Adrenergic Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Membrane Transport Modulators', 'Miscellaneous Central Nervous System Agents', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'QTc Prolonging Agents', 'Quinolizines', 'Vesicular Monoamine Transporter 2 Inhibitor', 'Vesicular Monoamine Transporter 2 Inhibitors']" +DB00408,Loxapine,Loxapineis a antipsychotic used for the treatment of schizophrenia.,"['P28223', 'P14416', 'P28335', 'P08908', 'P28222', 'P28221', 'P28566', 'P46098', 'P47898', 'P50406', 'P34969', 'P35348', 'P35368', 'P08913', 'P18089', 'P18825', 'P08588', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P21728', 'P21918', 'P35462', 'P21917', 'P21918', 'P35367', 'P25021', 'Q9H3N8', 'P31645', 'P23975', 'Q01959', 'P21728']","Loxapine, a dibenzoxazepine compound, represents a subclass of tricyclic antipsychotic agents, chemically distinct from the thioxanthenes, butyrophenones, and phenothiazines. Pharmacologically, Loxapine is a tranquilizer for which the exact mode of action has not been established, however, it is believed that by antagonising dopamine and serotonin receptors, there is a marked cortical inhibition which can manifest as tranquilization and suppression of aggression.",CN1CCN(CC1)C1=NC2=CC=CC=C2OC2=C1C=C(Cl)C=C2,"Loxapine is a dopamine antagonist, and also a serotonin -HT blocker. The exact mode of action of Loxapine has not been established, however changes in the level of excitability of subcortical inhibitory areas have been observed in several animal species in association with such manifestations of tranquilization as calming effects and suppression of aggressive behavior.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor BbinderHumansU-hydroxytryptamine receptor DbinderHumansU-hydroxytryptamine receptor EbinderHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor binderHumansU-hydroxytryptamine receptor binderHumansUAlpha-A adrenergic receptorbinderHumansUAlpha-B adrenergic receptorbinderHumansUAlpha-A adrenergic receptorbinderHumansUAlpha-B adrenergic receptorbinderHumansUAlpha-C adrenergic receptorbinderHumansUBeta- adrenergic receptorbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUMuscarinic acetylcholine receptor MbinderHumansUD() dopamine receptorbinderHumansUDopamine D receptorbinderHumansUDopamine D receptorbinderHumansUDopamine D receptorbinderHumansUHistamine H receptorbinderHumansUHistamine H receptorbinderHumansUHistamine H receptorbinderHumansUSodium-dependent serotonin transporterbinderHumansUSodium-dependent noradrenaline transporterbinderHumansUSodium-dependent dopamine transporterbinderHumansUDopamine D receptorantagonistHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Diazepines, Oxazepines, Thiazepines and Oxepines', 'Dibenzoxazepines', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Miscellaneous Antipsychotics', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB00862,Vardenafil,Vardenafilis a phosphodiesterase 5 inhibitor used to treat erectile dysfunction.,"['O76074', 'P18545', 'Q13956']","Vardenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), an enzyme responsible for the degradation of cGMP in the corpus cavernosum. The presence of cGMP in the corpus cavernosum leads to smooth muscle relaxation, an increased inflow of blood and an erection. Therefore, in patients with erectile dysfunction given vardenafil, normal sexual stimulation will increase cGMP levels in the corpus cavernosum. Without sexual stimulation and no cGMP production, vardenafil should not cause an erection.5,6Vardenafil should not be used in men for whom sexual activity is not recommended due to their underlying cardiovascular status. There is also a risk of developing prolonged erections that last longer than 4 hours, as well as priapism. In the event of a sudden loss of vision in one or both eyes, patients should stop using vardenafil. Patients taking PDE5 inhibitors, such as vardenafil, may also develop sudden hearing loss and experience a prolonged QT interval.5,6",CCCC1=NC(C)=C2N1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(CC)CC1,"Vardenafil inhibits cyclic guanosine monophosphate (GMP) specific phosphodiesterase type (PDE), which is responsible for the degradation of cyclic GMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cyclic GMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The tissue concentration of cyclic GMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs), and the most abundant PDE in the human corpus cavernosum is PDE. Therefore, the inhibition of PDE by vardenafil enhances erectile function by increasing the amount of cyclic GMP.TargetActionsOrganismAcGMP-specific ','-cyclic phosphodiesteraseinhibitorHumansURetinal rod rhodopsin-sensitive cGMP ','-cyclic phosphodiesterase subunit gammainhibitorallosteric modulatorHumansURetinal cone rhodopsin-sensitive cGMP ','-cyclic phosphodiesterase subunit gammainhibitorallosteric modulatorHumans",[],"['Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs Used in Erectile Dysfunction', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Imidazoles', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Piperazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Urological Agents', 'Urologicals', 'Vasodilating Agents']" +DB01019,Bethanechol,Bethanecholis a muscarinic agonist used to treat postoperative and postpartum nonobstructive functional urinary retention and neurogenic atony of the bladder with retention.,"['P20309', 'P11229', 'P08172', 'P08173', 'P08912']",Bethanechol is selective for muscarinic receptors and has little to no impact on nicotinic receptors.1The charged quaternary amine in the structure of bethanechol prevents it from crossing the blood-brain barrier which minimizes central nervous system related adverse effects.1,CC(C[N+](C)(C)C)OC(N)=O,"Bethanechol is a direct muscarinic agonist and stimulates the parasympathetic nervous system by binding to postganglionic muscarinic receptors.,Though there are types of muscarinic receptors (M, M, M, M, M), binding of bethanechol to M is most clinically significant since M receptors are present in intestinal smooth muscle and the bladder.The cholinergic effects of bethanechol lead to increased detrusor muscle tone to promote bladder emptying and increased smooth muscle tone which restores gastrointestinal peristalsis and motility.As a result of selectivity for muscarinic receptors, bethanechol produces minimal to no nicotinic effects.TargetActionsOrganismAMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumansUMuscarinic acetylcholine receptor MagonistHumans",[],"['Acids, Acyclic', 'Amines', 'Ammonium Compounds', 'Autonomic Agents', 'Bethanechol Compounds', 'Carbamates', 'Choline Esters', 'Cholinergic Agents', 'Cholinergic Agonists', 'Muscarinic Agonists', 'Nervous System', 'Neurotransmitter Agents', 'Nitrogen Compounds', 'Onium Compounds', 'Parasympathomemetic (Cholinergic) Agents', 'Parasympathomimetics', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds', 'Trimethyl Ammonium Compounds']" +DB09232,Cilnidipine,Cilnidipineis a dihydropyridine calcium channel blocker with action on both N- and L-type calcium channels used to treat hypertension.,"['Q00975', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555']",Administration of cilnidipine has been shown to present an antisympathetic profile in vitro and in vivo. It decreases blood pressure safely and effectively without excessive blood pressure reduction or tachycardia.2,COCCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1,"Cilnidipine acts on the L-type calcium channels of blood vessels by blocking the incoming calcium and suppressing the contraction of blood vessels, thereby reducing blood pressure. Cilnidipine also works on the N-type calcium channel located at the end of the sympathetic nerve, inhibiting the emission of norepinephrine and suppressing the increase in stress blood pressure.TargetActionsOrganismAVoltage-dependent N-type calcium channel subunit alpha-BantagonistHumansAVoltage-dependent L-type calcium channelantagonistHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Pyridines', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB01203,Nadolol,"Nadololis a non-selective beta-adrenergic antagonist used for the management of arrhythmias, angina pectoris, and hypertension.","['P08588', 'P07550']","Nadolol is a nonselective beta adrenal receptor blocker that is used to lower blood pressure.8,9It has a long duration of action as it is usually taken once daily and a wide therapeutic index as patients start at doses of 40mg daily but may be increased to doses as high as 240mg daily.8,9Patients taking nadolol should not aburptly stop taking it as this may lead to exacerbation of ischemic heart disease.8,9",CC(C)(C)NCC(O)COC1=CC=CC2=C1C[C@H](O)[C@H](O)C2,"Although nadolol is described as a non selective beta blocker, it does not interact with beta adrenal receptors.Antagonism of beta- and beta- adrenoceptors in the heart inhibits cyclic AMP and its signalling pathway, decreasing the strength and speed of contractions as well as the speed of relaxation and conduction.Antagonism of beta- adrenoceptors in the smooth muscle cells of the vasculature inhibits their relaxation, leading to an increase in peripheral vascular resistance and reducing the risk of severe hypotension.The increase in peripheral vascular resistance may contribute to the decrease in insulin sensitivity associated with nadolol use.Antagonism of beta- adrenoceptors in the juxtaglomerular apparatus of the kidney inhibits the release of renin, and therefore angiotensin II mediated vasoconstriction, aldosterone mediated water retention, and the release of epinephrine.Antagonism of beta- adrenoceptors in the liver and skeletal muscle inhibits glycogenolysis, in the lungs prevents bronchodilation, and in the pancrease inhibits insulin release.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Autonomic Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Non-Selective', 'Beta Blocking Agents, Non-Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'Negative Inotrope', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Photosensitizing Agents', 'Propanolamines', 'Propanols', 'Sympatholytics']" +DB01173,Orphenadrine,Orphenadrineis a muscarinic antagonist used as an adjunct for the symptomatic relief of musculoskeletal pain and discomfort.,"['O15399', 'Q05586', 'O60391', 'Q8TCU5', 'P35367', 'P23975', 'Q9Y5Y9']","Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anaesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favourable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. The effect is somewhat less on bradykinesia.",CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1C,"Orphenadrine binds and inhibits both histamine H receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect.TargetActionsOrganismAGlutamate receptor ionotropic, NMDA DantagonistHumansAGlutamate receptor ionotropic, NMDA antagonistHumansAGlutamate receptor ionotropic, NMDA BantagonistHumansAGlutamate receptor ionotropic, NMDA AantagonistHumansAHistamine H receptorantagonistHumansASodium-dependent noradrenaline transporterinhibitorHumansUSodium channel protein type subunit alphainhibitorHumans",[],"['Agents producing tachycardia', 'Amines', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Autonomic Agents', 'Benzene Derivatives', 'Benzhydryl Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally-mediated Muscle Relaxation', 'Cholinergic Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Ethers, Chemically Close to Antihistamines', 'Ethylamines', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Miscellaneous Skeletal Muscle Relaxants', 'Muscarinic Antagonists', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Nervous System', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB13944,Testosterone enanthate,Testosterone enanthateis an androgen used to treat low or absent testosterone.,"['P10275', 'P03372', 'P08235']","Administration of ester derivatives of testosterone as testosterone enanthate generates an increase in serum testosterone to levels reaching 400% from the baseline within 24 hours of administration. These androgen levels remain elevated for 3-5 days after initial administration.5Continuous administration of testosterone enanthate shows a significant suppression of dihydrotestosterone, serum PSA, HDL and FSH, as well as a slight increase in serum estradiol. The levels of dihydrotestosterone and FSH can remain suppressed even 14 days after treatment termination. There are no changes in mood and sexual activity by the presence of testosterone enanthate.6",[H][C@@]12CC[C@H](OC(=O)CCCCCC)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to α-dihydrotestosterone (DHT) by the cytoplasmic enzyme α-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about . times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing androgen effects.Such activities are useful as endogenous androgens like testosterone and dihydrotestosterone are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution.Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).TargetActionsOrganismAAndrogen receptoragonistHumansUEstrogen receptor alphaNot AvailableHumansUMineralocorticoid receptorNot AvailableHumans",[],"['Adrenal Cortex Hormones', 'Androgens', 'Androstanes', 'Androstenes', 'Androstenols', 'BCRP/ABCG2 Substrates', 'Contraceptive Agents, Male', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OAT3/SLC22A8 Inducers', 'P-glycoprotein inhibitors', 'Steroids', 'Testosterone and derivatives', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors']" +DB06819,Phenylbutyric acid,"Phenylbutyric acidis an agent indicated for the adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in specific enzymes, including the neonatal-onset deficiency and late-onset disease with a history of hyperammonemic encephalopathy.","['P95468', 'Q13547', 'Q969S8', 'Q96DB2', 'Q92769', 'O15379', 'P56524', 'Q9UQL6', 'Q9UBN7', 'Q8WUI4', 'Q9BY41', 'Q9UKV0']","Phenylbutyric acid decreases elevated plasma ammonia glutamine levels in patients with urea cycle disorders. It increases waste nitrogen excretion in the form of phenylacetylglutamine.2In the intestines, phenylbutyric acid was shown to reduce mucosal inflammation, regulate transepithelial fluid transport, and improve oxidative status. Some studies report antineoplastic properties of phenylbutyric acid, showing that phenylbutyric acid can promote growth arrest and apoptosis of cancer cells. It is suggested that phenylbutyric acid can act as an ammonia scavenger, chemical chaperone, and histone deacetylase inhibitor.1",OC(=O)CCCC1=CC=CC=C1,"Sodium phenylbutyrate is the most commonly used salt used in drug products of phenylbutyric acid. Sodium phenylbutyrate is a pro-drug that rapidly metabolizes to phenylacetate.Phenylacetate is conjugated with phenylacetyl-CoA, which in turn combines with glutamine via acetylation to form phenylacetylglutamine. Phenylacetylglutamine is then excreted by the kidneys, thus providing an alternate mechanism of waste nitrogen excretion to the urea cycle.Phenylacetylglutamine is comparable to urea, as each molecule contains two moles of nitrogen.TargetActionsOrganismUAromatic-amino-acid aminotransferaseNot AvailableParacoccus denitrificansUHistone deacetylaseinhibitorHumans",[],"['Acids, Carbocyclic', 'Alimentary Tract and Metabolism', 'Ammonium Ion Binding Activity', 'Antineoplastic Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Nitrogen Binding Agent', 'Urea Cycle Disorder Agents', 'Various Alimentary Tract and Metabolism Products']" +DB00947,Fulvestrant,Fulvestrantis an estrogen receptor antagonist used to treat HR+ breast cancer that may also be HER2-.,['P03372'],Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects.,[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H],"Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines.TargetActionsOrganismAEstrogen receptor alphaantagonistHumans",[],"['Anti-Estrogens', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Estrogen Antagonists', 'Estrogen Receptor Antagonists', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Selective Estrogen Receptor Modulators', 'Steroids', 'UGT1A1 Substrates']" +DB01407,Clenbuterol,Clenbuterolis a decongestant and bronchodilator used in a variety of respiratory conditions.,"['P07550', 'P08588', 'P13945', 'P01138', 'P01375']","Clenbuterol is a substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. Although approved for use in some countries, as of fall, 2006, clenbuterol is not an ingredient of any therapeutic drug approved by the U.S. Food and Drug Administration.",CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(Cl)=C1,Clenbuterol is a Beta() agonist similar in some structural respects to salbutamol. Agonism of the beta() receptor stimulates adenylyl cyclase activity which ultimately leads to downstream effects of smooth muscle relaxation in the bronchioles.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumansUBeta-nerve growth factorstimulatorHumansUTumor necrosis factorother/unknownHumans,[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Drugs for Obstructive Airway Diseases', 'Ethanolamines', 'Long-acting beta-adrenoceptor agonists', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists', 'Sympathomimetics']" +DB01261,Sitagliptin,Sitagliptinis an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used for the management of type 2 diabetes mellitus.,['P27487'],"Sitagliptin inhibits DPP-4 which leads to increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), decreased levels of glucagon, and a stronger insulin response to glucoseLabel,4,1,2.",N[C@@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F,"Inhibition of DPP- by sitagliptin slows DPP- mediated inactivation of incretins like GLP- and GIPLabel,. Incretins are released throughout the day and upregulated in response to meals as part of glucose homeostasisLabel,. Reduced inhibition of incretins increase insulin synthesis and decrease glucagon release in a manner dependant on glucose concentrationsLabel,. These effects lead to an overall increase in blood glucose control which is demonstrated by reduced glycosylated hemoglobin (HbAc)Label,.TargetActionsOrganismADipeptidyl peptidase inhibitorHumans",[],"['Agents causing angioedema', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'DPP-IV Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypoglycemia-Associated Agents', 'Incretins', 'OAT3/SLC22A8 Substrates', 'Oral Hypoglycemics', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Triazoles']" +DB01435,Antipyrine,"Antipyrineis an antipyretic agent used for the symptomatic treatment of acute otitis media, most commonly in combination with benzocaine.","['P35354', 'P23219']","Antipyrine is an analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29)",CN1N(C(=O)C=C1C)C1=CC=CC=C1,"Antipyrine is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-, COX-, and COX- enzymes involved in prostaglandin (PG) synthesis.TargetActionsOrganismUProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",['Buccopharyngeal anesthesia'],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics and Anesthetics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Methemoglobinemia Associated Agents', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'Otologicals', 'Peripheral Nervous System Agents', 'Pyrazoles', 'Pyrazolones', 'Sensory Organs', 'Sensory System Agents']" +DB01130,Prednicarbate,Prednicarbateis a medium potency topical corticosteroid used to manage pruritus and inflammation associated with responsive skin conditions.,['P04150'],"Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocytes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids.",[H][C@@]12CC[C@](OC(=O)OCC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"In common with other topical corticosteroids, prednicarbate has anti-inflammatory, antipruritic, and vasoconstrictive properties. In general, the mechanism of the anti-inflammatory activity of topical steroids is unclear. However, corticosteroids are thought to act by the induction of phospholipase A inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Steroids']" +DB00146,Calcifediol,Calcifediolis an active metabolite of vitamin D used to treat hyperparathyroidism as well as to combat hypocalcemia in dialysis patients.,['P11473'],"Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma.",C[C@H](CCCC(C)(C)O)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C,"Calcidiol is transformed in the kidney by -hydroxyvitamin D--(alpha)-hydroxylase to calcitriol, the active form of vitamin D. Calcitriol binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.TargetActionsOrganismAVitamin D receptoragonistHumans",[],"['Alimentary Tract and Metabolism', 'Anti-Parathyroid Agents', 'Bone Density Conservation Agents', 'Calcium Homeostasis', 'Cholestanes', 'Cholestenes', 'Diet, Food, and Nutrition', 'Food', 'Fused-Ring Compounds', 'Lipids', 'Membrane Lipids', 'Micronutrients', 'Physiological Phenomena', 'Secosteroids', 'Steroids', 'Sterols', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB05458,Pozanicline,"ABT-089 is a neuronal nicotinic acetylcholine receptor agonist that may have therapeutic utility for the treatment of several neurological disorders including Alzheimer, Attention Deficit Hyperactivity Disorder and Schizophrenia/Schizoaffective disorders. In radioligand binding studies, ABT-089 has shown selectivity toward the alpha4beta2 nAChR subtype as compared to the alpha7 and alpha1beta1deltagamma nAChR subtypes. Neuronal nicotinic acetylcholine receptors (nAChRs) modulate the release of several important neurotransmitters, such as acetylcholine and dopamine.","['P43681', 'P17787']","ABT-089 is a neuronal nicotinic acetylcholine receptor agonist. Neuronal nicotinic acetylcholine receptors (nAChRs) modulate the release of several important neurotransmitters, such as acetylcholine and dopamine.",CC1=C(OC[C@@H]2CCCN2)C=CC=N1,"ABT- is a neuronal nicotinic acetylcholine receptor agonist. In radioligand binding studies, ABT- has shown selectivity toward the alphabeta nAChR subtype as compared to the alpha and alphabetadeltagamma nAChR subtypes.TargetActionsOrganismUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumans",[],[] +DB01037,Selegiline,Selegilineis a monoamine oxidase inhibitor used to treat major depressive disorder and Parkinson's.,"['P27338', 'P21397']",Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine. Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO-B. It also may prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells.,C[C@H](CC1=CC=CC=C1)N(C)CC#C,"Although the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. Selegiline binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Selegiline may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monozmine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.TargetActionsOrganismAAmine oxidase [flavin-containing] BinhibitorHumansNAmine oxidase [flavin-containing] AinhibitorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Amines', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Enzyme Inhibitors', 'Ethylamines', 'Hypotensive Agents', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase B Inhibitors', 'Monoamine Oxidase Inhibitors', 'Nervous System', 'Neuroprotective Agents', 'P-glycoprotein inhibitors', 'Phenethylamines', 'Protective Agents', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01018,Guanfacine,Guanfacineis an alpha-2A adrenergic receptor agonist used to treat ADHD.,"['P08913', 'P18089']","Guanfacine is a selective alpha-2A adrenergic receptor agonist but it is unclear how this translates to the treatment of ADHD.11It has a long duration of action as it is given once daily and a wide therapeutic window as fatal overdoses have not been described in literature.11Patients should be counselled regarding the risk of hypotension, bradycardia, and syncope.11",NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl,"Guanfacine is a selective alpha-A adrenergic receptor agonist, which reduces the effects of the sympathetic nervous system on the heart and circulatory system.The link between guanfacine’s molecular mechanism and it’s effect on the treatment of ADHD has not been determined.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansUAlpha-B adrenergic receptorbinderHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amidines', 'Antiadrenergic Agents, Centrally Acting', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Central alpha-2 Adrenergic Agonist', 'Central Alpha-agonists', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Guanidines', 'Hypotensive Agents', 'Imidazoline Receptor Agonists', 'MATE 1 Inhibitors', 'MATE inhibitors', 'Neurotransmitter Agents', 'OCT1 inhibitors', 'OCT1 substrates', 'OCT2 Substrates']" +DB00289,Atomoxetine,Atomoxetineis a selective norepinephrine reuptake inhibitor (SNRI) used in the management of Attention Deficit Hyperactivity Disorder (ADHD).,"['P23975', 'P31645', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391', 'P48549', 'P41145']","Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor used for the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine has been shown to specifically increase norepinephrine and dopamine within the prefrontal cortex, which results in improved ADHD symptoms.8,8,18Due to atomoxetine's noradrenergic activity, it also has effects on the cardiovascular system such as increased blood pressure and tachycardia.11Sudden deaths, stroke, and myocardial infarction have been reported in patients taking atomoxetine at usual doses for ADHD. Atomoxetine should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure or heart rate such as certain patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. It should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experienced clinically important increases in blood pressure or heart rate. Although the role of atomoxetine in these cases is unknown, consideration should be given to not treating patients with clinically significant cardiac abnormalities. Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac evaluation.18In general, particular care should be taken in treating ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in patients at risk for bipolar disorder. Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by atomoxetine at usual doses. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine, and discontinuation of treatment should be considered.18Atomoxetine capsules increased the risk of suicidal ideation in short-term studies in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). All pediatric patients being treated with atomoxetine should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.18Postmarketing reports indicate that atomoxetine can cause severe liver injury. Although no evidence of liver injury was detected in clinical trials of about 6000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to atomoxetine use in postmarketing experience. Rare cases of liver failure have also been reported, including a case that resulted in a liver transplant. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. Laboratory testing to determine liver enzyme levels should be done upon the first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained “flu like” symptoms).18",CNCC[C@@H](OC1=CC=CC=C1C)C1=CC=CC=C1,"Atomoxetine is known to be a potent and selective inhibitor of the norepinephrine transporter (NET),which prevents cellular reuptake of norepinephrine throughout the brain, which is thought to improve the symptoms of ADHD. More recently, positron emission tomography (PET) imaging studies in rhesus monkeys have shown that atomoxetine also binds to the serotonin transporter (SERT),and blocks the N-methyl-d-aspartate (NMDA) receptor,indicating a role for the glutamatergic system in the pathophysiology of ADHD.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent serotonin transporterbinderHumansUNMDA receptorblockerHumansUG protein-activated inward rectifier potassium channel inhibitorHumansUKappa-type opioid receptorpartial agonistHumans",[],"['Adrenergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Membrane Transport Modulators', 'Miscellaneous Central Nervous System Agents', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Reuptake Inhibitor', 'Norepinephrine Uptake Inhibitors', 'Potential QTc-Prolonging Agents', 'Propylamines', 'Psychostimulants, Agents Used for ADHD and Nootropics', 'QTc Prolonging Agents']" +DB00118,Ademetionine,"Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)","['P21964', 'Q8N1G2', 'Q9HBK9', 'Q14749', 'P17707', 'P31153', 'P35520', 'Q00266']","S-adenosylmethionine is an intermediate metabolite of methionine. Its involvement in methylation assists in cellular growth and repair, maintains the phospho-bilipid layer in cell membranes. It also helps in the maintenance of the action of several hormones and neurotransmitters that affect mood. Highest concentration are found in the brain and the liver.",C[S+](CC[C@H](N)C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2N,"S-Adenosylmethionine (SAMe) is a natural substance present in the cells of the body. It is a direct metabolite of the essential amino acid L-methionine. SAMe plays a crucial biochemical role in the body by donating a one-carbon methyl group in a process called transmethylation. SAMe, formed from the reaction of L-methionine and adenosine triphosphate catalyzed by the enzyme S-adenosylmethionine synthetase, is the methyl-group donor in the biosynthesis of both DNA and RNA nucleic acids, phospholipids, proteins, epinephrine, melatonin, creatine and other molecules.TargetActionsOrganismUCatechol O-methyltransferasecofactorHumansUCap-specific mRNA (nucleoside-'-O-)-methyltransferase Not AvailableHumansUArsenite methyltransferaseNot AvailableHumansUGlycine N-methyltransferasecofactorHumansUS-adenosylmethionine decarboxylase proenzymecofactorHumansUS-adenosylmethionine synthase isoform type-cofactorHumansUCystathionine beta-synthaseactivatorHumansUS-adenosylmethionine synthase isoform type-cofactorHumans",[],"['Alimentary Tract and Metabolism', 'Amino Acids', 'Amino Acids and Derivatives', 'Amino Acids, Peptides, and Proteins', 'Amino Acids, Sulfur', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dietary Supplements', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Purine Nucleosides', 'Purines', 'Ribonucleosides', 'Sulfur Compounds', 'Supplements']" +DB00151,Cysteine,Cysteineis an amino acid commonly found as a component of total parenteral nutrition and used as an antidote for acetaminophen overdose.,"['P48507', 'P48506', 'P17174', 'P00505', 'P32929', 'P35520', 'P49589', 'P16455', 'P48637', 'Q9HA77', 'Q9Y600', 'Q9Y697', 'Q16878']","Due to this ability to undergo redox reactions, cysteine has antioxidant properties. Cysteine is an important source of sulfur in human metabolism, and although it is classified as a non-essential amino acid, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes. Cysteine may at some point be recognized as an essential or conditionally essential amino acid.",N[C@@H](CS)C(O)=O,"Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available. Cysteine is typically synthesized in the human body when there is sufficient methionine available. Cysteine exhibits antioxidant properties and participates in redox reactions. Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms. Glutathione (GSH) typically requires biosynthesis from its constituent amino acids, cysteine, glycine, and glutamic acid, due to its limited systemic availability. Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate. In human metabolism, cysteine is also involved in the generation of sulfide present in iron-sulfur clusters and nitrogenase by acting as a precursor. In a report released by five top cigarette companies, cysteine is one of the additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).TargetActionsOrganismUGlutamate--cysteine ligase regulatory subunitNot AvailableHumansUGlutamate--cysteine ligase catalytic subunitNot AvailableHumansUAspartate aminotransferase, cytoplasmicsubstrateHumansUAspartate aminotransferase, mitochondrialsubstrateHumansUCystathionine gamma-lyaseNot AvailableHumansUCystathionine beta-synthaseNot AvailableHumansUCysteine--tRNA ligase, cytoplasmicsubstrateHumansUMethylated-DNA--protein-cysteine methyltransferaseNot AvailableHumansUGlutathione synthetaseNot AvailableHumansUProbable cysteine--tRNA ligase, mitochondrialsubstrateHumansUCysteine sulfinic acid decarboxylaseNot AvailableHumansUCysteine desulfurase, mitochondrialNot AvailableHumansUCysteine dioxygenase type Not AvailableHumans","['Total parenteral nutrition therapy', 'Amino acid supplementation']","['Amino Acids', 'Amino Acids, Neutral', 'Amino Acids, Peptides, and Proteins', 'Amino Acids, Sulfur', 'Caloric Agents', 'Cysteine', 'Dietary Supplements', 'Nutritional Support', 'Proteinogenic Amino Acids', 'Sulfhydryl Compounds', 'Sulfur Compounds', 'Supplements']" +DB03766,Propanoic acid,Propanoic acidis an antimicrobial food additive.,"['P10724', 'Q9NQX3', 'P96965']","As a naturally occurring carboxylic acid, propionic acid typically undergoes metabolism via conversion to propionyl coenzyme A (propionyl-CoA), which is part of the usual metabolic pathway that carboxylic acids participate within in the human body2,7. Most of propionic acid's antibacterial and preservative activities subsequently stem from this metabolic pathway as the metabolic fate of propionates varies in different microorganisms, resulting in antimicrobial mechanisms of action that may revolve around differing propionate metabolites causing competition, inhibition, and/or interference effects along other metabolic pathways in the various microorganisms affected7.In the human body, however, propionic acid is generally metabolized with little ill effect and ultimately becomes a chemical intermediate in the citric acid cycle7.",CCC(O)=O,"The metabolic fate of propionates varies in different microorganisms. Some have enzyme systems that can convert succinate to propionyl-coenzyme A and through various further steps to propionate, CO, or propionyl phoshpate. Still others can convert propionic acid to B-alanine or directly to CO. Whatever the case, the inhibiting effect for microbials is likely related to competition with acetate in the acetokinase system, to the blockage of pyruvate conversion to acetyl-coenzyme A and to interference with B-alanine in pantothenic acid syntheses.Moreover, other studies suggest the antimicrobial activity of propionic acid revolves around its ability to reduce the pH of its immediate environment to levels of acidity that are harmful to pathogenic microbes as well as its ability to dissociate such that its lipid soluble undissociated form is capable of entering microbial cells. Additionally, there are also studies that suggest that propionic acid's antifungal activity may be the result of propionyl-CoA inhibiting glucose metabolism in certain species of fungus via the accumulation of the CoA-derivative.TargetActionsOrganismUAlanine racemaseNot AvailableGeobacillus stearothermophilusUGephyrinNot AvailableHumansU-hydroxy--oxo--methylocta-,-dienoate hydrolaseNot AvailablePseudomonas fluorescens",[],"['Acids, Acyclic', 'Anti-Infective Agents', 'Fatty Acids', 'Fatty Acids, Volatile', 'Lipids', 'Ophthalmologicals', 'Sensory Organs']" +DB00360,Sapropterin,Sapropterinis a cofactor used as an adjunct to phenylalanine restriction in the treatment of phenylketonuria (PKU).,"['P00439', 'P29474', 'P07101', 'P17752']","Tetrahydrobiopterin (BH4) is used to convert several amino acids, including phenylalanine, to other essential molecules in the body including neurotransmitters. Tetrahydrobiopterin deficiency can be caused by mutations in GTP cyclohydrolase 1 (GCH1), 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (PCBD1), 6-pyruvoyltetrahydropterin synthase (PTS), and quinoid dihydropteridine reductase (QDPR) genes. These genes make the enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. High levels of phenylalanine can result in signs and symptoms ranging from temporary low muscle tone to mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.",[H][C@@]1(CNC2=C(N1)C(=O)NC(N)=N2)[C@@H](O)[C@H](C)O,"Tetrahydrobiopterin (BH) is a natural co-factor or co-enzyme for phenylalanine--hydroxylase (PAH),Tetrahydrobiopterine, and tryptophan--hydroxylase. Tetrahydrobiopterin is also a natural co-factor for nitrate oxide synthase. Therefore BH is required for the conversion of phenylalanine to tyrosine, for the production of epinephrine (adrenaline) and the synthesis of the monoamine neuro-transmitters, serotonin, dopamine, and norepinephrine (noradrenaline). It is also involved in apoptosis and other cellular events mediated by nitric oxide production. As a coenzyme, BH reacts with molecular oxygen to form an active oxygen intermediate that can hydroxylate substrates. In the hydroxylation process, the co-enzyme loses two electrons and is regenerated in vivo in an NADH-dependent reaction. As a co-factor for PAH, tetrahydrobiopterin allows the conversion of phenylalanine to tyrosine and reduces the level of phenylalanine in the bloodstream, thereby reducing the toxic effects of of this amino acid. Normal serum concentrations of phenylalanine are micomolar, while elevated (toxic) levels are typically > micromolar. Individuals with a deficiency in tetrahydrobiopterin are not able to efficiently convert phenylalanine to tyrosine. The excess levels provided by tetrahydrobiopterin supplementation help improve enzyme efficiency. As a co-factor for tyrosine hydroxylase, BH facilitates the conversion of tyrosine to L-dopa while as a co-factor for tryptophan hydroxylase, BH allows the conversion of tryptophan to -hydroxytryptophan, which is then converted to serotonin.TargetActionsOrganismAPhenylalanine--hydroxylasecofactorHumansANitric oxide synthase, endothelialcofactorHumansATyrosine -monooxygenasecofactorHumansATryptophan -hydroxylase cofactorHumans",[],"['Alimentary Tract and Metabolism', 'Amines', 'BCRP/ABCG2 Inhibitors', 'Coenzymes', 'Dietary Supplements', 'Enzymes and Coenzymes', 'Ethylamines', 'Heterocyclic Compounds, Fused-Ring', 'Nitric Oxide Synthase', 'Other Miscellaneous Therapeutic Agents', 'P-glycoprotein inhibitors', 'Phenethylamines', 'Phenylalanine Hydroxylase Activator', 'Phenylalanine Hydroxylase Activators', 'Pteridines', 'Pterins', 'Supplements', 'Various Alimentary Tract and Metabolism Products']" +DB00924,Cyclobenzaprine,Cyclobenzaprineis a skeletal muscle relaxant that works on the brainstem to treat muscle spasms of local origin.,"['P28223', 'P41595', 'P28335', 'P50406', 'P31645', 'P23975', 'P34969', 'O00206', 'Q06278']","Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear.15,16,10Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours.10Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications.15,16,5Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.15,16",CN(C)CCC=C1C2=CC=CC=C2C=CC2=CC=CC=C12,"The exact mechanism of action of cyclobenzaprine has not been fully elucidated in humans, and much of the information available regarding its mechanism has been ascertained from early animal studies. There is some evidence that cyclobenzaprine exerts its effects at the supraspinal level, specifically within the locus coeruleus of the brainstem, with little-to-no action at neuromuscular junctions or directly on skeletal musculature,. Action on the brainstem is thought to result in diminished activity of efferent alpha and gamma motor neurons, likely mediated by inhibition of coeruleus-spinal or reticulospinal pathways, and ultimately depressed spinal cord interneuron activity.More recently it has been suggested that inhibition of descending serotonergic pathways in the spinal cord via action on -HT receptors may contribute to cyclobenzaprine’s observed effects.,,TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor antagonistHumansUSodium-dependent serotonin transporterinhibitorHumansUSodium-dependent noradrenaline transporterinhibitorHumansU-hydroxytryptamine receptor antagonistHumansUToll-like receptor inhibitorHumansUAldehyde oxidaseinhibitorHumans",[],"['Agents that reduce seizure threshold', 'Antidepressive Agents', 'Benzocycloheptenes', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally-mediated Muscle Relaxation', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dibenzocycloheptenes', 'Drugs causing inadvertant photosensitivity', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Neurotoxic agents', 'Photosensitizing Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents', 'UGT1A4 substrates']" +DB00820,Tadalafil,"Tadalafilis a phosphodiesterase 5 inhibitor used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension.","['O76074', 'Q9HCR9', 'P18545']","Tadalafil exerts a therapeutic effect in ED by increasing sexual stimulation-dependant smooth muscle relaxation in the penis, allowing the corpus cavernosum to fill with blood to produce an erection.2,3Smooth muscle relaxation in the pulmonary vasculature helps to produce vasodilation in PAH which reduces blood pressure in the pulmonary arteries.3In BPH, tadalafil may contribute to decreased smooth muscle cell proliferation which may reduce the size of the prostate and relieve the anatomical obstruction which produces urinary symptoms of BPH.4The decreased affinity of tadalafil for PDE6 compared to other PDE5 inhibitors may explain the reduced incidence of visual side effects.8,9,2",[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C1,"Tadalafil is a selective phosphodiesterase- (PDE) inhibitor that produces several downstream effects with the most common therapeutic effect being smooth muscle relaxation.Patients may experience ED due to a variety of causes including psychogenic, neurogenic, vasculogenic, iatrogenic, or endocrine.These causes result in dysfunction of penile smooth muscle relaxation through either disrupted neuronal signaling or direct influence on smooth muscle cells. During sexual arousal, non-adrenergic non-cholinergic (NANC) neurons release nitric oxide (NO). Nitric oxide stimulates guanylate cyclase which converts guanosine triphosphate to cyclic guanosine monophosphate (cGMP).,cGMP activates the cGMP-dependent kinase (PKG) in a signal cascade which activates K+ channels leading to inhibition of Ca+ channels, inhibits platelet activation, and inhibits smooth muscle cell proliferation while inducing apoptosis. This signal cascade is attenuated by PDE which breaks the phosphodiester bond of cGMP, converting it to GMP. Inhibition of PDE by tadalafil increases signaling via the PKG cascade which supports penile smooth muscle relaxation during sexual arousal by decreasing Ca+ entry into smooth muscle cells. This smooth muscle relaxation allows blood to fill the corpus cavernosum thereby producing an erection.In PAH, blood pressure in the pulmonary arteries is raised due to a variety of mechanisms stemming from endothelial dysfunction.Decreased production of NO and prostacyclin reduce vasodilatory signaling while overproduction of endothelin- and thromboxane increase vasoconstriction. Inflammation, thromboses, and hypoxia later contribute to vascular remodeling which further reduces luminal size. The resultant increase in blood pressure reduces the capacity for gas exchange and increases afterload at the right ventricle, producing symptoms of dyspnea, fatigue, and dizziness as well as leading to right-sided heart failure. Tadalafil exerts its therapeutic effect in PAH through boosting NO-cGMP signaling to contribute to smooth muscle relaxation as with ED.Lastly, tadalafil is used to treat BPH.BPH produces urinary dysfunction through hyperproliferation of the epithelial and smooth muscle layers of the prostate.The increased size of the prostate blocks urine flow through the urethra resulting in higher residual volumes due to incomplete emptying. Tadalafil does not appear to exert its benefit via smooth muscle relaxation of the prostate. It may instead exert its effect through a mix of increased oxygenation and decreased inflammation, which decreases tissue remodeling, and inhibition of cell proliferation through the cGMP cascade.The decreased affinity for PDE compared to other PDE inhibitors may explain the decreased incidence of visual side effects as PDE is present in the eye and contributes to color vision.,,TargetActionsOrganismAcGMP-specific ','-cyclic phosphodiesteraseinhibitorHumansNDual ','-cyclic-AMP and -GMP phosphodiesterase AinhibitorHumansNRetinal rod rhodopsin-sensitive cGMP ','-cyclic phosphodiesterase subunit gammainhibitorHumans",[],"['5-alpha Reductase Inhibitors', 'Antihypertensive Agents', 'Antihypertensives for Pulmonary Arterial Hypertension', 'Carbolines', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Benign Prostatic Hypertrophy', 'Drugs Used in Erectile Dysfunction', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Pyridines', 'Urological Agents', 'Urologicals', 'Vasodilating Agents']" +DB00356,Chlorzoxazone,Chlorzoxazoneis a drug with muscle relaxant properties that is used as an adjunct to physical therapy and analgesics to treat stiffness and pain caused by a variety of musculoskeletal conditions.,['Q12791'],Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles.,ClC1=CC2=C(OC(=O)N2)C=C1,"Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasmTargetActionsOrganismACalcium-activated potassium channel subunit alpha-Not AvailableHumans",[],"['Benzoxazoles and derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally-mediated Muscle Relaxation', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Oxazol, Thiazine, and Triazine Derivatives', 'Peripheral Nervous System Agents']" +DB01250,Olsalazine,Olsalazineis an anti-inflammatory aminosalicylate used in the treatment of inflammatory bowel disease and ulcerative colitis.,"['P23219', 'P35354', 'P51580', 'P01579', 'P47989']","Olsalazine is an anti-inflammatory agent that blocks the production of cyclooxygenase (COX)-derived products of arachidonic acid metabolism.5It works to alleviate inflammation in ulcerative colitis.1Olsalazine was shown to decrease water and sodium absorption. While olsalazine is not expected to affect the motility and transit time of small intestines, it decreased small bowel transit time at high doses ranging from 60 to 120 mg/kg. In about 40% of the patients with ulcerative colitis, administration of olsalazine 1g daily was associated with a decrease in whole gut transit time.1",OC(=O)C1=CC(=CC=C1O)\N=N\C1=CC=C(O)C(=C1)C(O)=O,"Upon administration, the azo bond connecting two molecules of mesalamine (also known as -aminosalicylic acid or -ASA) is cleaved by azoreductase-containing bacteria in the colon. The two molecules of mesalamine are released to mediate therapeutic effects.The exact mechanism of action of olsalazine and its active moiety mesalamine in ulcerative colitis has not been elucidated; however, it is understood that mesalamine mediates an anti-inflammatory action on epithelial cells of the colon.The COX-derived (i.e., prostanoids such as prostaglandin E) and lipoxygenase-derived products (i.e., leukotrienes [LTs] and hydroxyeicosatetraenoic acids [HETEs]) of arachidonic acid metabolism have been implicated in the pathogenesis and maintenance of inflammatory disorders, including ulcerative colitis and inflammatory bowel disease.,Mesalamine may attenuate inflammation by blocking the COX enzyme and inhibiting prostaglandin production in the colon.,,Olsalazine was also shown to inhibit xanthine oxidase, an enzyme that generates oxygen-derived free radicals.Olsalazine may attenuate intestinal inflammation by limiting macrophage migration to inflamed intestinal mucosa: it was shown to inhibitin vitromigration of intestinal macrophages in response to leukotriene B. Olsalazine may also act as a free radical scavenger, and mesalazine may suppress fatty acid peroxidation.TargetActionsOrganismAHuman CyclooxygenasesinhibitorHumansAThiopurine S-methyltransferaseinhibitorHumansAInterferon gammaNot AvailableHumansUXanthine dehydrogenase/oxidaseinhibitorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Aminosalicylate', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Benzene Derivatives', 'Benzoates', 'Gastrointestinal Agents', 'Hydroxy Acids', 'Hydroxybenzoates', 'Intestinal Antiinflammatory Agents', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Phenols', 'Salicylates', 'Sensory System Agents']" +DB01161,Chloroprocaine,"Chloroprocaineis a local anesthetic agent indicated for intrathecal injection in adults for the production of subarachnoid block, spinal anesthesia, or ocular surface anesthesia.","['P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q01959']","Chloroprocaine is an ester local anesthetic agent indicated for the production of local or regional anesthesia with effects on the cardiovascular and central nervous systems. Compared with lidocaine and bupivacaine, chloroprocaine has shorter ambulation and discharge times.2Chloroprocaine has minimal effects on cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance at therapeutic doses.3,4However, at toxic blood concentrations, chloroprocaine may cause atrioventricular block and cardiac arrest, as well as decreased cardiac output and arterial blood pressure. A high concentration of chloroprocaine in plasma can also lead to central nervous system stimulation, depression, or both. Some signs of central stimulation include restlessness, tremors and shivering, which may progress to convulsions. Depression, coma and respiratory arrest may also occur. As with other local anesthetics, patients may experience depression of the central nervous system without a prior stage of stimulation.3,4",CCN(CC)CCOC(=O)C1=C(Cl)C=C(N)C=C1,"Chloroprocaine acts mainly by binding to the alpha subunit on the cytoplasmic region of voltage-gated sodium channels and inhibiting sodium influx in neuronal cell membranes.This lowers the nerve membrane permeability to sodium and decreases the rate of rise of the action potential.,Therefore, chloroprocaine inhibits signal conduction and leads to a reversible nerve conduction blockade.The progression of anesthesia depends on the diameter, myelination and conduction velocity of nerve fibers, and the order of loss of nerve function is the following: ) pain, ) temperature, ) touch, ) proprioception, and ) skeletal muscle tone.,TargetActionsOrganismAVoltage-gated sodium channel alpha subunitinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumans","['Infiltration anesthesia therapy', 'Local Anaesthesia therapy', 'Ocular surface anesthesia', 'Peripheral Nerve Blocks', 'Spinal Anesthesia therapy', 'Caudal epidural block therapy', 'Lumbar epidural anesthesia therapy']","['Acids, Carbocyclic', 'Aminobenzoates', 'Anesthetics', 'Anesthetics, Local', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase substrates', 'Esters of Aminobenzoic Acid', 'Local Anesthesia', 'Local Anesthetics (Ester)', 'Nervous System', 'para-Aminobenzoates', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB01106,Levocabastine,Levocabastineis a selective histamine H1 receptor antagonist indicated for the management of seasonal allergic conjunctivitis symptoms.,"['P35367', 'O95665']",Levocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis can be inhibited by levocabastine. Levocabastine can also reduce symptoms of allergic rhinitis by preventing an increase in vascular permeability of nasal mucosa.,C[C@@H]1CN(CC[C@]1(C(O)=O)C1=CC=CC=C1)[C@H]1CC[C@](CC1)(C#N)C1=CC=C(F)C=C1,"Levocabastine is a potent, selective histamine H-receptor antagonist. It works by competing with histamine for H-receptor sites on effector cells. It thereby prevents, but does not reverse, responses mediated by histamine alone. Levocabastine does not block histamine release but, rather, prevents histamine binding and activity. Levocabastine also binds neurotensin receptors and serves as a neurotensin agonist. This can induce some degree of analgesia.TargetActionsOrganismAHistamine H receptorantagonistHumansANeurotensin receptor type partial antagonistHumans",[],"['Anti-Allergic Agents', 'Antiallergic Agents, Excl. Corticosteroids', 'Central Nervous System Depressants', 'Decongestants and Antiallergics', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Nasal Preparations', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sensory Organs']" +DB01079,Tegaserod,Tegaserodis a serotonin-4 (5-HT4) receptor agonist indicated for the treatment of constipation predominant irritable bowel syndrome (IBS-C) specifically in women under the age of 65. There is currently no safety or efficacy data for use of tegaserol in men.,"['Q13639', 'P28335', 'P28223', 'P41595']","In general, it has been determined that tegaserod is an agonist of serotonin type-4 (5-HT(4)) receptors, an antagonist at 5-HT(2B) receptors, but is expected to possess minimal binding to 5-HT(1) receptors, and virtually no affinity for 5-HT(3) or dopamine receptors1,3,6.In clinical trials with tegaserod, centrally analyzed ECGs were recorded in 4,605 male and female patients receiving tegaserod 6 mg twice daily or placebo for IBS-C and other related motility disorders6,8. No subject receiving the agent had an absolute QTcF above 480 ms6,8. An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving tegaserod and 8% receiving placebo6,8. An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively6,8. The effects of tegaserod on the QTcF interval were ultimately not considered to be clinically meaningful6,8.Furthermore, it was determined that there is a potential for tegaserod and its main metabolite (the M29 metabolite) to increase platelet aggregation in vitro6,8. In one in vitro study, at concentrations up to 10-times the maximum plasma concentration (Cmax) at the recommended dose, tegaserod significantly increased platelet aggregation in a concentration-dependent manner up to 74% (range 11% to 74%) compared to a control vehicle (with potentiation by various agonists)6,8. In another in vitro study, the M29 metabolite, at concentrations up to 0.6-times the Cmax of M29 also showed a 5% to 16% increase in platelet aggregation compared to the control vehicle6,8. The clinical implications of these in vitro platelet aggregation results remain unclear6,8.",CCCCCNC(=N)N\N=C\C1=CNC2=C1C=C(OC)C=C2,"Irritable bowel syndrome (IBS) is a complex functional disorder comprised of various abnormal and discomforting effects on the gastrointestinal tract and bowel function,,,. Although the cause of IBS has yet to be formally elucidated, patient experience has demonstrated that the disorder is typically associated with abdominal pain, abdominal distension, cramping or bloating, variations in urgency for bowel movements, feelings of incomplete evacuation, gastroesophageal reflux, and various other effects,,,. In particular, IBS that features constipation as a predominant effect is categorized as constipation-predominant IBS, or IBS-C,.Concurrently, -Hydroxytryptamine (-HT, or serotonin) has demonstrated the ability to elicit significant regulatory actions on gastrointestinal motility. Specifically, it has been shown that the activation of -HT() receptors located on motor neurons and interneurons in the gastrointestinal wall can cause the release of acetylcholine, substance P, and calcitonin gene-related peptide that can all facilitate the propulsion of material through the gut. Moreover, when -HT() receptors located in smooth muscle cells are also activated, activities that may alleviate symptoms of IBS-C like esophageal relaxation and the inhibition of human colonic circular muscle contraction can also occur. Additionally, activating -HT() on enteric neurons and enterocytes also cause natural fluid secretion in the gut - an action which also strongly assists in promoting the movement of content along the gastrointestinal tract.Alternatively, it has also been observed that -HT may participate in generating visceral hyperalgesia in IBS, an observation supported in part by the finding of increased amounts of -HT and its metabolites in the plasma of patients experiencing IBSIt has therefore also been proposed that antagonism of -HT(B) receptors can lead to inhibition of both -HT mediated gastrointestinal motility and visceral hypersensitivity.Subsequently, because tegaserod is considered to be an agonist of the -HT() receptor and an antagonist of the -HT(B) receptor at clinically relevant levels, it is believed that tegaserod may elicit its mechanism of action by facilitating activities associated with the activation and antagonism of the -HT() and -HT(B) receptors, like stimulating peristaltic gastrointestinal reflexes and intestinal secretion, inhibiting visceral sensitivity, enhancing basal motor activity, and normalizing impaired motility throughout the gastrointestinal tract, among other actions,,,,.TargetActionsOrganismA-hydroxytryptamine receptor antagonistpartial agonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'BCRP/ABCG2 Substrates', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Constipation', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Laxatives', 'P-glycoprotein substrates', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 4 Receptor Agonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Serotonin-4 Receptor Agonist']" +DB09216,Tolfenamic acid,"Tolfenamic acid, with the formula N-(2-methyl-3-chlorphenyl)-anthranilic acid, is a nonsteroidal anti-inflammatory agent.2It was discovered by scientists at Medica Pharmaceutical Company in Finland. It is used in the UK as a treatment for migraine under the name of Clotam.10In the US, it presents a Status class I by the FDA. By the European Medicine Agency, it was granted in 2016 with the status of orphan for the treatment of supranuclear palsy.9","['P23219', 'P35354']","Studies have shown that tolfenamic acid presents a non-dose dependent partial inhibition of irritant-induced temperature rise as well as a dose-dependent inhibition of skin edema. By studying its NSAID properties more closely, it was noted a dose-related inhibition of serum thromboxane which indicated the inhibition of COX-1. In the same line, there was noted a inhibition of prostaglandin E2 synthesis which marks a related COX-2 inhibition.3The maximal inhibition of thromboxane was greater than 80% as well as is proven to be a potent prostaglandin E inhibitor.4",CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O,"Tolfenamic acid inhibits the biosynthesis of prostaglandins, and it also presents inhibitory actions on the prostaglandin receptors.As commonly thought, the mechanism of action of tolfenamic acid is based on the major mechanism of NSAIDs which consists of the inhibition of COX- and COX- pathways to inhibit prostaglandin secretion and action and thus, to exert its anti-inflammatory and pain-blocking action. Nonetheless, some report currently indicates that tolfenamic acid inhibits leukotriene B chemotaxis of human polymorphonuclear leukocytes leading to an inhibition of even % of the chemotactic response. This activity is a not ligand specific additional anti-inflammatory mechanism of tolfenamic acid.TargetActionsOrganismAProstaglandin G/H synthase antagonistHumansAProstaglandin G/H synthase antagonistHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Aminobenzoates', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzoates', 'Bradycardia-Causing Agents', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fenamates', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Membrane Transport Modulators', 'Migraine Disorders, drug therapy', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Neurotransmitter Agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Prostaglandin Antagonists', 'Sensory System Agents']" +DB00809,Tropicamide,Tropicamideis a muscarinic receptor antagonist used to induce mydriasis and cycloplegia for diagnostic procedures.,"['P08173', 'P11229', 'P08172', 'P20309']","Tropicamide is an anticholinergic drug and that works by non‐selectively blocking muscarinic receptors to cause mydriasis and cycloplegia. It relaxes the pupillary sphincter to dilate the pupil.1The onset of tropicamide‐induced mydriasis is about 10 to 15 minutes,3with optimal effect occurring 25 to 30 minutes post-administration. Mydriasis caused by tropicamide wears off within four to eight hours, but it was seen up to 24 hours in some individuals. Tropicamide hinders accommodation by causing the contraction of the ciliary muscle. The cycloplegic effect occurs within 20 to minutes following administration, with a duration of action of four to 10 hours. Tropicamide can elevate intraocular pressure.1The ophthalmic use of tropicamide is not typically associated with serious systemic adverse events.5One randomized pilot study showed that oral tropicamide alleviated perceived symptoms of sialorrhea in patients with Parkinson's Disease: anticholinergics are believed to restore the dopaminergic to cholinergic activity imbalance in neurodegenerative diseases.1Similarly in one case report, tropicamide administered via ophthalmic solution relieved clozapine-induced sialorrhea.2Interestingly, in rodent models, tropicamide suppressed drug-induced tremulous jaw movements which are often used as a model of parkinsonian tremor: the significance of this finding requires further investigations.4",CCN(CC1=CC=NC=C1)C(=O)C(CO)C1=CC=CC=C1,"Muscarinic acetylcholine receptors are involved in numerous ocular functions. The Msubtype is predominantly expressed by smooth muscle cells of the sphincter pupillae, which is a circular muscle of the iris, and ciliary muscles. In response to light or binding of acetylcholine, Mreceptor signalling leads to contraction of the sphincter pupillae and pupil constriction. Contraction of the ciliary muscle via Mreceptor signalling also leads to accommodation, adjusting the lens for near vision.The eye is also innervated by parasympathetic nerves: ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction.Tropicamide is a non-selective muscarinic antagonist that binds to all subtypes of muscarinic receptors. By binding to muscarinic receptors, tropicamide relaxes the pupillary sphincter muscle and causes pupil dilation.By blocking the muscarinic receptors of the ciliary body, tropicamide also prevents accommodation.Like other muscarinic antagonists, tropicamide inhibits the parasympathetic drive, allowing the sympathetic nervous system responses to dominate.Tropicamide is thought to ameliorate sialorrhea by blocking Mreceptors expressed on salivary glands and reducing hypersalivation.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",['Diagnostic procedures'],"['Anticholinergic Agents', 'Autonomic Agents', 'Cholinergic Agents', 'Muscarinic Antagonists', 'Mydriatics', 'Mydriatics and Cycloplegics', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Pyridines', 'Sensory Organs']" +DB00935,Oxymetazoline,"Oxymetazolineis an alpha-1A adrenoceptor agonist used to treat nasal congestion, allergic reactions of the eye, and facial erythema associated with rosacea.","['P35348', 'P08913', 'P18089', 'P18825', 'P35368', 'P25100', 'P08908', 'P28222', 'P28221', 'P08909']","Oxymetazoline is an adrenergic α1- and α2-agonist and a direct-acting sympathomimetic drug. By stimulating adrenergic receptors, oxymetazoline causes vasoconstriction of dilated arterioles and reduces blood flow.16In a radioligand competition study, oxymetazoline displayed higher affinity at α1A-adrenoceptors compared to α2B-adrenoceptors, but with higher potency at α2B-adrenoceptors.5When sprayed intranasally, oxymetazoline relieved relief nasal congestion and improved nasal airflow in patients with acute coryzal rhinitis for up to 12 hours following a single dose.10An earlyin vitrostudy demonstrated oxymetazoline to exert anti-oxidant actions, where it inhibited microsomal lipid peroxidation and mediated hydroxyl radical scavenging activity. This suggests that oxymetazoline has a beneficial effect against oxidants, which play a role in tissue damage in inflammation.11",CC1=CC(=C(O)C(C)=C1CC1=NCCN1)C(C)(C)C,"Oxymetazoline binds to α- and α-adrenoceptors, which are Gq- and Gi-protein-coupled receptors respectively. α-adrenoceptors agonism promotes vascular smooth muscle contraction by increasing intracellular calcium levels through activating phospholipase C, while α-adrenoceptors agonism, specifically the αB-adrenoceptors, can also elicit vasoconstriction through the inhibition of adenyl cyclase.,,,Rosacea is a condition characterized by transient and persistent facial erythema. By stimulating αA-adrenoceptors and causing vasoconstriction, oxymetazoline is believed to diminish the symptoms of erythema.In blepharoptosis, it is hypothesized that oxymetazoline works by stimulating α-adrenergic receptors on the Müller muscle that elevates the upper eyelid, causing muscle contraction.Oxymetazoline is used in combination with tetracaine for local anesthesia in dentistry. Such combination use adds beneficial effects: the vasoconstrictor counteracts the local anesthetic agent's vasodilatory action, thereby constricting dilated arterioles and reducing blood flow to the application area.,Oxymetazoline relieves nasal congestion by vasoconstricting the respiratory microvasculature, in both resistance and capacitance blood vessels on the human nasal mucosa, leading to decreased nasal mucosal blood flow, edema, and airflow resistance.,TargetActionsOrganismAAlpha-A adrenergic receptorpartial agonistHumansAAlpha-A adrenergic receptoragonistpartial agonistHumansAAlpha-B adrenergic receptoragonistHumansUAlpha-C adrenergic receptoragonistHumansUAlpha-B adrenergic receptoragonistHumansUAlpha-D adrenergic receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor BagonistHumansU-hydroxytryptamine receptor DagonistHumansU-hydroxytryptamine receptor Cpartial agonistRat",['Airway visualization'],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Autonomic Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 Substrates', 'Decongestants and Antiallergics', 'Dermatologicals', 'Imidazoles', 'Increased Sympathetic Activity', 'Nasal Decongestants', 'Nasal Preparations', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Sensory Organs', 'Sympathomimetics', 'Sympathomimetics Used as Decongestants', 'Sympathomimetics, Plain', 'UGT1A9 Substrates', 'Vasoconstriction', 'Vasoconstrictor Agents']" +DB00991,Oxaprozin,"Oxaprozinis an NSAID used to treat osteoarthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis.","['P23219', 'P35354']","Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain.",OC(=O)CCC1=NC(=C(O1)C1=CC=CC=C1)C1=CC=CC=C1,"Anti-inflammatory effects of Oxaprozin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Oxaprozin is a non-selective NSAID, with a cell assay system showing lower COX- selectivity implying higher COX- selectivity.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Acyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Cyclooxygenase Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Other Nonsteroidal Anti-inflammatory Agents', 'Oxazoles', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Propionates', 'Sensory System Agents']" +DB00720,Clodronic acid,"Clodronic acidis a bisphosphonate used to treat osteoporosis in postmenopausal women, hypercalcemia of malignancy, and osteolysis.","['P12235', 'P05141', 'P12236']","Clodronic acid is a first generation bisphosphonate that inhibits osteoclast mediated bone resorption.8It has a wide therapeutic index as a large overdose is required for significant toxicity and a long duration of action due to the slow release from bone.8Patients should be counselled regarding the risk of hypocalcemia, hypovolemia, renal insufficiency, transient hyperphosphatemia, and transient hyperparathyroidism.8",OP(O)(=O)C(Cl)(Cl)P(O)(O)=O,"Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis.Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.Osteoclasts mediate resorption of bone.When osteoclasts bind to bone they form podosomes, ring structures of F-actin.Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.First generation bisphosphonates closely mimic the structure of pyrophosphate, which can be incorporated into ATP anologues that cannot be hydrolyzed, disrupting all ATP mediated actions of osteoclasts.TargetActionsOrganismAHydroxylapatiteantagonistHumansAADP/ATP translocase inhibitorHumansAADP/ATP translocase inhibitorHumansAADP/ATP translocase inhibitorHumans",[],"['Bisphosphonates', 'Bone Density Conservation Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Musculo-Skeletal System', 'Organophosphonates', 'Organophosphorus Compounds']" +DB01137,Levofloxacin,"Levofloxacinis a fluoroquinolone antibiotic used to treat infections caused by susceptible bacteria of the upper respiratory tract, skin and skin structures, urinary tract, and prostate, as well as for post-exposure treatment of inhaled anthrax and the plague.","['P43700', 'P43702']","Levofloxacin is bactericidal and exerts its antimicrobial effects via inhibition of bacterial DNA replication.9It has a relatively long duration of action in comparison with other antibiotics that allows for once or twice daily dosing. Levofloxacin is associated with QTc-interval prolongation and should be used with caution in patients with other risk factors for prolongation (e.g. hypokalemia, concomitant medications).9Levofloxacin has demonstratedin vitroactivity against a number of aerobic gram-positive and gram-negative bacteria and may carry some activity against certain species of anaerobic bacteria9and other pathogens such asChlamydiaandLegionella.1Resistance to levofloxacin may develop, and is generally due to mutations in DNA gyrase or topoisomerase IV, or via alterations to drug efflux.9,7Cross-resistance may occur between levofloxacin and other fluoroquinolones, but is unlikely to develop between levofloxacin and other antibiotic classes (e.g. macrolides) due to significant differences in chemical structure and mechanism of action.9As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.",C[C@H]1COC2=C3N1C=C(C(O)=O)C(=O)C3=CC(F)=C2N1CCN(C)CC1,"Levofloxacin, like other fluoroquinolone antibiotics, exerts its antimicrobial activity via the inhibition of two key bacterial enzymes: DNA gyrase and topoisomerase IV.Both targets are type II topoisomerases, but have unique functions within the bacterial cell. DNA gyrase is an enzyme found only in bacteria that introduces negative supercoils into DNA during replication - this helps to relieve torsional strain caused by the introduction of positive supercoils during replication, and these negative supercoils are essential for chromosome condensation and the promotion of transcription initiation.It is comprised of four subunits (two A subunits and two B subunits) of which the A subunits appear to be the target of fluoroquinolone antibiotics.Bacterial topoisomerase IV, in addition to contributing to the relaxation of positive supercoils, is essential at the terminal stages of DNA replication and functions to “unlink” newly replicated chromosomes to allow for the completion of cell division.Inhibition of these enzymes by levofloxacin likely occurs via complexation with the topoisomerase enzymes.The end result is a blockade of DNA replication, thus inhibiting cell division and resulting in cell death.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)",[],"['Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Fluoroquinolone Antibacterial', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 2 Inhibitors', 'MATE inhibitors', 'MATE substrates', 'Moderate Risk QTc-Prolonging Agents', 'OAT1/SLC22A6 Substrates', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Ophthalmologicals', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Renal Agents', 'Sensory Organs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01616,Alverine,"Alverineis a smooth muscle relaxant used to relieve abdominal pain associated with gastrointestinal conditions like heartburn, flatulence, and Irritable Bowel Syndrome.",['P08908'],"Alverine is a smooth muscle relaxant. Smooth muscle is a type of muscle that is not under voluntary control; it is the muscle present in places such as the gut and uterus. Alverine acts directly on the muscle in the gut, causing it to relax. This prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. Diverticular disease is a condition in which small pouches form in the gut lining. These pouches can trap particles of food and become inflamed and painful. In irritable bowel syndrome the normal activity of the gut muscle is lost. The muscle spasms result in symptoms such as heartburn, abdominal pain and bloating, constipation or diarrhoea. By relaxing the gut muscle, alverine citrate relieves the symptoms of this condition. Alverine also relaxes the smooth muscle in the womb (uterus). It is therefore also used to treat painful menstruation, which is caused by muscle spasms in the uterus (dysmenorrhea).",CCN(CCCC1=CC=CC=C1)CCCC1=CC=CC=C1,TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumans,[],"['Alimentary Tract and Metabolism', 'Amines', 'Antidepressive Agents', 'Autonomic Agents', 'Central Nervous System Depressants', 'Drugs for Functional Gastrointestinal Disorders', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB01084,Emedastine,Emedastineis a selective H1-receptor antagonist used topically to manage symptoms of allergic conjunctivitis.,['P35367'],Emedastine is a relatively selective H1-receptor antagonist.,CCOCCN1C(=NC2=CC=CC=C12)N1CCCN(C)CC1,"Emedastine is a relatively selective, histamine Hantagonist. In vitro examinations of emedastine's affinity for histamine receptors demonstrate relative selectivity for the Hhistamine receptor. In vivo studies have shown concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration. Emedastine appears exert negligible effects on adrenergic, dopaminergic and serotonin receptors.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Anti-Allergic Agents', 'Decongestants and Antiallergics', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Inhibitors', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'Ophthalmologicals', 'QTc Prolonging Agents', 'Sensory Organs']" +DB01015,Sulfamethoxazole,"Sulfamethoxazoleis an oral sulfonamide antibiotic, given in combination with trimethoprim, used to treat a variety of infections of the urinary tract, respiratory system, and gastrointestinal tract.",['P0AC13'],"Sulfamethoxazole is a bacteriostatic sulfonamide antibiotic that inhibits a critical step in bacterial folate synthesis. It is generally given in combination withtrimethoprim, a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid.9Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either trimethoprim or sulfamethoxazole alone, as together they inhibit sequential steps in the bacterial folate synthesis pathway.9Sulfonamides, including sulfamethoxazole, have been implicated in hypersensitivity reactions - these agents should be discontinued at the first sign of a developing rash, as this may signal the start of a more severe reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Sulfamethoxazole treatment may contribute to folate deficiency and should therefore be used with caution in patients at a higher risk of developing a deficiency. Hemolysis has been observed in patients with glucose-6-phosphate dehydrogenase deficiency who are using sulfamethoxazole/trimethoprim.9",CC1=CC(NS(=O)(=O)C2=CC=C(N)C=C2)=NO1,"Sulfamethoxazole is a sulfonamide that inhibits bacterial dihydrofolic acid synthesis due to its structural similarity to an endogenous substrate, para-aminobenzoic acid (PABA).,Most bacteria meet their need for folic acid by synthesizing it from PABA, as opposed to Animalia that require exogenous folic acid sources.Sulfamethoxazole competitively inhibits dihydropteroate synthase, the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid.Inhibition of this pathway prevents the synthesis of tetrahydrofolate and, ultimately, the synthesis of bacterial purines and DNA, resulting in a bacteriostatic effect.TargetActionsOrganismADihydropteroate synthaseantagonistEscherichia coli (strain K)",[],"['Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Amines', 'Aniline Compounds', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Pneumocystis Pneumonia', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs for Treatment of Tuberculosis', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Intermediate-Acting Antibacterial Sulfonamides', 'Methemoglobinemia Associated Agents', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfanilamides', 'Sulfonamide Antibacterial', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds']" +DB00213,Pantoprazole,"Pantoprazoleis a proton pump inhibitor used to treat erosive esophagitis, gastric acid hypersecretion, and to promote healing of tissue damage caused by gastric acid.","['P20648', 'O94760']","This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion.16General EffectsPantoprazole has been shown to reduce acid reflux-related symptoms, heal inflammation of the esophagus, and improve patient quality of life more effectively than histamine-2 receptor antagonists (H2 blockers). This drug has an excellent safety profile and a low incidence of drug interactions. It can be used safely in various high-risk patient populations, including the elderly and those with renal failure or moderate hepatic dysfunction.1Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinalC. difficile), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.12PPIs such as pantoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes14,15.A note on laboratory testing abnormalitiesDuring treatment with antisecretory medicinal products such as pantoprazole, serum gastrin (a peptide hormone that stimulates secretion of gastric acid) increases in response to the decreased acid secretion caused by proton pump inhibition. The increased gastrin level may interfere with investigations for neuroendocrine tumors. Published evidence suggests that proton pump inhibitors should be stopped 14 days before chromogranin A (CgA) measurements. This permits chromogranin A levels, that might be falsely elevated after proton pump inhibitor treatment, to return to the normal reference range.21Reports have been made of false-positive results in urine screening tests for tetrahydrocannabinol (THC) in patients receiving the majority of proton pump inhibitors, including pantoprazole. A confirmatory method should be used.21",COC1=C(OC)C(CS(=O)C2=NC3=C(N2)C=C(OC(F)F)C=C3)=NC=C1,"Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach.ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid).Proton pump inhibitors such as pantoprazole are substitutedbenzimidazolederivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in thecanaliculi(small canal) of the gastric parietal cell, an acidic environment, to activesulfenamidederivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function.Specifically, pantoprazole binds to thesulfhydryl groupof H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion.The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H() antagonists.TargetActionsOrganismAPotassium-transporting ATPase alpha chain inhibitorHumansNN(G),N(G)-dimethylarginine dimethylaminohydrolase inhibitorHumans",[],"['2-Pyridinylmethylsulfinylbenzimidazoles', 'Acid Reducers', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Benzimidazoles', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Proton Pump Inhibitors', 'Proton-pump Inhibitors', 'Pyridines', 'Sulfoxides', 'Sulfur Compounds']" +DB06144,Sertindole,Sertindoleis an atypical antipsychotic indicated in the treatment of schizophrenia.,"['P14416', 'P28223', 'P28335', 'P50406', 'Q12809', 'P35348', 'P35368', 'P25100']","Sertindole is an atypical antipsychotic at least as effective as haloperidol and risperidone in the treatment of neuroleptic-responsive schizophrenia. Sertindole improves negative symptoms, and is also effective for the treatment of neuroleptic-resistant schizophrenia. Sertindole is generally well tolerated and is associated with a low rate of extrapyramidal symptoms (EPS).",FC1=CC=C(C=C1)N1C=C(C2CCN(CCN3CCNC3=O)CC2)C2=C1C=CC(Cl)=C2,"Sertindole is an antipsychotic drug with affinity for dopamine D, serotonin -HTA and -HTC, and alpha-adrenoreceptors. Preclinical studies suggest that sertindole acts preferentially on limbic and cortical dopaminergic neurons and clinical trials have confirmed that sertindole is effective at a low dopamine D occupancy level.TargetActionsOrganismADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor CantagonistHumansA-hydroxytryptamine receptor antagonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUAlpha-A adrenergic receptorNot AvailableHumansUAlpha-B adrenergic receptorNot AvailableHumansUAlpha-D adrenergic receptorNot AvailableHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Indole Derivatives', 'Nervous System', 'Neurotoxic agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB01267,Paliperidone,Paliperidoneis an atypical antipsychotic used in the treatment of schizophrenia and other schizoaffective or delusional disorders.,"['P28223', 'P14416', 'P21917', 'P35462', 'P28335', 'P35367', 'P35348', 'P35368', 'P28221', 'P08913', 'P18089', 'P18825', 'P08908', 'P21728', 'P34969']","Paliperidone is an atypical antipsychotic developed by Janssen Pharmaceutica. Chemically, paliperidone is primary active metabolite of the older antipsychotic risperidone (paliperidone is 9-hydroxyrisperidone). The mechanism of action is unknown but it is likely to act via a similar pathway to risperidone.",CC1=C(CCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C(=O)N2CCCC(O)C2=N1,"Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown, but it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of central dopamine Type (D) and serotonin Type (HTA) receptor antagonism.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor CantagonistHumansUHistamine H receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansU-hydroxytryptamine receptor DantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptoragonistHumansU-hydroxytryptamine receptor AantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor Not AvailableHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Highest Risk QTc-Prolonging Agents', 'Hyperglycemia-Associated Agents', 'Isoxazoles', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Psycholeptics', 'Psychotropic Drugs', 'Pyrimidines', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT1D Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB11757,Istradefylline,Istradefyllineis a selective adenoside A2A receptor antagonist indicated in adjunct to levodopa and carbidopa for the treatment of Parkinson's Disease.,"['P29274', 'P30542']","Istradefylline is a selective adenosine A2Areceptor inhibitor.1,2It has a long duration of action as it is given once daily and has a half life of 64-69 hours.1,2,8Patients taking this medication should be monitored for dyskinesia, hallucinations, and lack of impulse control.8Consider dose reductions for these patients.8",[H]\C(=C(\[H])C1=CC(OC)=C(OC)C=C1)C1=NC2=C(N1C)C(=O)N(CC)C(=O)N2CC,"Istradefylline is a selective adenosine AAreceptor inhibitor.,These receptors are found in the basal ganglia, a region of the brain that suffers degeneration in Parkinson's disease, and is also significantly involved in motor control.AAreceptors are also expressed on GABAergic medium spiny neurons within the indirect striato-pallidal pathway.The GABAergic action of this pathway is thereby reduced.Istradefylline has times the affinity for AAreceptors than Areceptors.TargetActionsOrganismAAdenosine receptor AaantagonistHumansNAdenosine receptor AantagonistHumans",[],"['Adenosine A2 Receptor Antagonists', 'Anti-Parkinson Drugs', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'MATE 1 Inhibitors', 'MATE 2 Inhibitors', 'MATE inhibitors', 'Nervous System', 'Neurotransmitter Agents', 'OAT1/SLC22A6 inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'P-glycoprotein inhibitors', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P1 Receptor Antagonists']" +DB09225,Zotepine,"Zotepine, with the formula (2-chloro-11-(2-dimethyl-amino-ethoxy)-dibenzo thiepin, is a neuroleptic drug. It was designed and synthesized by Fujisawa Pharmaceutical Co Ltd.1It has been used as an antipsychotic in Japan, India and some places in Europe like UK and Germany since 1980's.2Zotepine was never approved by the FDA. In 1993, it was classified as inactive drug substance (Status I, Type II) and in 1995 the FDA studied the manufacturing procedures of Zotepine tablets in Germany, but the status remained inactive.9When the analysis of antipsychotics was retaken in 2016 by the FDA, zotepine did not reach the threshold effect to be further studied.10. In the EMA, by 2015 it was under pharmacovigilance studies for the potential treatment of acute renal failure.11","['P21728', 'P21918', 'P14416', 'P28223', 'P34969', 'P23975', 'P31645', 'P50406']","In preclinical studies, zotepine is characterized by the presence of a strong antiserotonergic activity when compared with other neuroleptic drugs. It has also been reported to present elevations in the seizure threshold in the amygdaloid nucleus.1When zotepine's effects were analyzed by electroencephalography, it was noted a typical response of a low-potency neuroleptics of the sedative type. Administration of zotepine has shown improvements in numerical movements and complex reaction. These effects tend to be accompanied by increases in pulse rate, increase in prolactin levels and some typical neuroleptic side effects.3,4",CN(C)CCOC1=CC2=CC=CC=C2SC2=CC=C(Cl)C=C12,"Zotepine is a dopamine antagonist that has a high affinity for D- and D-like receptors. It presents a strong antagonism for several serotonin receptors, such as -HTa, -HTc, -HT and -HT. Zotepine activities are also related to the inhibition of noradrenaline reuptake and serotonergic activity. All these effects allow zotepine to improve the negative and cognitive symptoms of schizophrenia.TargetActionsOrganismAD() dopamine receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor antagonistHumansASodium-dependent noradrenaline transporterantagonistHumansASodium-dependent serotonin transporterantagonistHumansU-hydroxytryptamine receptor antagonistHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Psycholeptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thiepins', 'Tranquilizing Agents']" +DB06216,Asenapine,Asenapineis an atypical antipsychotic used to treat patients with bipolar I disorder and patients with schizophrenia.,"['P28223', 'P14416', 'P08908', 'P28222', 'P41595', 'P28335', 'P47898', 'P50406', 'P34969', 'P35462', 'P21917', 'P21728', 'P35348', 'P08913', 'P18089', 'P18825', 'P35367', 'P25021', 'P08588', 'P07550']","Asenapine is a serotonin, dopamine, noradrenaline, and histamine antagonist in which asenapine possess more potent activity with serotonin receptors than dopamine. Sedation in patients is associated with asenapine's antagonist activity at histamine receptors. Its lower incidence of extrapyramidal effects are associated with the upregulation of D1 receptors. This upregulation occurs due to asenapine's dose-dependent effects on glutamate transmission in the brain. It does not have any significant activity with muscarinic, cholinergic receptors therefore symptoms associated with anticholinergic drug activity like dry mouth or constipation are not expected to be observed. Asenapine has a higher affinity for all aforementioned receptors compared to first-generation and second-generation antipsychotics except for 5-HT1A and 5-HT1B receptors.",CN1CC2C(C1)C1=C(OC3=CC=C(Cl)C=C23)C=CC=C1,"Asenapine is an atypical antipsychotic multireceptor neuroleptic drug which shows strong HTA (serotonin) and D (dopamine) receptor antagonism, which has been shown to enhance dopamine (DA) and acetylcholine (Ach) efflux in rat brains. Asenapine may improve cognitive function and negative symptoms in patients with schizophrenia.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansADopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor antagonistHumansU-hydroxytryptamine receptor antagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumansUHistamine H receptorantagonistHumansUHistamine H receptorantagonistHumansUBeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumans",['Maintenance therapy'],"['Acid Reducers', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Benzocycloheptenes', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diazepines, Oxazepines, Thiazepines and Oxepines', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H2 Antagonists', 'Hyperglycemia-Associated Agents', 'Nervous System', 'Neurotoxic agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents', 'UGT1A4 substrates']" +DB09286,Pipamperone,"Pipamperone is a typical antipsychotic of thebutyrophenonefamily used in the treatment of schizophrenia. It was developed by Janssen Pharmaceutica in 1961 and started its first round of clinical trials in 196311,15.","['P14416', 'P28223', 'P35348', 'P35368', 'P25100', 'P21917', 'P21728', 'P35462', 'P41595', 'P08913']","Pipamperone is an antipsychotic medication that has sedative effects, which may be beneficial in the management of agitation and disordered sleep8. Pipamperone, showing antidopaminergic and anti-serotonergic properties, has been noted for its anti- +agitation effects and for its ability to normalize sleep rhythms in psychiatric patients5. One study showed that pipamperone increased the expression of D4 (dopaminergic) receptors, explaining its helpfulness in decreasing positive psychotic symptoms, such as delusions and hallucinations19.",NC(=O)C1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)N1CCCCC1,"Pipamperone binds mainly to -HTA receptors, with a nearly equal affinity to D receptors and a moderate affinity for -HTC, D, D, - and B-adrenoceptors.This drug is a selective -HTA, D and D antagonist,. Extrapyramidal adverse effects also appear to be limited in pipamperone treatment compared to traditional antipsychotic medications due to its high receptor selectivity.Pipamperone has a -fold higher affinity for D than D receptors. It has been suggested that D receptors may play a role in the modulation of GABAergic neuronal activity by dopamine.TargetActionsOrganismUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor AagonistHumansUAlpha- adrenergic receptorsantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorNot AvailableHumansU-hydroxytryptamine receptor BNot AvailableHumansUAlpha-A adrenergic receptorantagonistHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Butyrophenone Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Hypotensive Agents', 'Ketones', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB01184,Domperidone,"Domperidoneis a dopamine receptor antagonist used as a peristaltic stimulant and anti-emetic agent for dyspepsia, indigestion, epigastric pain, nausea, and vomiting.","['P35462', 'P14416']","Domperidone is a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.",ClC1=CC2=C(C=C1)N(C1CCN(CCCN3C(=O)NC4=CC=CC=C34)CC1)C(=O)N2,"Domperidone acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant. The gastroprokinetic properties of domperidone are related to its peripheral dopamine receptor blocking properties. Domperidone facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure. Antiemetic: The antiemetic properties of domperidone are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level. It has strong affinities for the D and D dopamine receptors, which are found in the chemoreceptor trigger zone, located just outside the blood brain barrier, which - among others - regulates nausea and vomitingTargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antiemetics', 'Autonomic Agents', 'Benzimidazoles', 'Central Nervous System Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs for Functional Gastrointestinal Disorders', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Piperidines', 'Prokinetic Agents', 'Propulsives', 'QTc Prolonging Agents']" +DB00508,Triflupromazine,A phenothiazine used as an antipsychotic agent and as an antiemetic.,"['P14416', 'P21728', 'P41595', 'P11229', 'P08172']","Triflupromazine is a member of a class of drugs called phenthiazines, which are dopamine D1/D2 receptor antagonists. Phenothiazines are used to treat serious mental and emotional disorders, including schizophrenia and other psychotic disorders. It reduces anxiety, emotional withdrawal, hallucinations, disorganized thoughts, blunted mood, and suspiciousness. Triflupromazine is used particularly to control violent behavior during acute episodes of psychotic disorders. It can also be used to control severe nausea and vomiting, severe hiccups, and moderate to severe pain in some hospitalized patients. Triflupromazine acts on the central nervous system.",CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(C=C2)C(F)(F)F,Triflupromazine binds to the dopamine D and dopamine D receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D neurotransmitter receptors in the chemoreceptor trigger zone (CTZ) and vomiting centre. Triflupromazine blocks the neurotransmitter dopamine and the vagus nerve in the gastrointestinal tract. Triflupromazine also binds the muscarinic acetylcholine receptors (M and M) and the tryptamine D receptors (HTB).TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor BantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans,[],"['Agents producing tachycardia', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antiemetics', 'Antipsychotic Agents', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Peripheral Nervous System Agents', 'Phenothiazines', 'Phenothiazines With Aliphatic Side-Chain', 'Psycholeptics', 'Psychotropic Drugs', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB08922,Perospirone,"Perospirone is an atypical or second-generation antipsychotic of the azapirone family that antagonizes serotonin 5HT2A receptors and dopamine D2 receptors. It also displays affinity towards 5HT1A receptors as a partial agonist. Dainippon Sumitomo Pharma developed perospirone in Japan in 2001 for the treatment of acute schizophrenia and bipolar mania as well as chronic schizophrenia. It is commonly present as the hydrated hydrochloride salt form. Classified as a neuroleptic agent, perospirone is shown to be effective against positive, negative and general symptoms in patients with schizophrenia1. It is also shown to be less associated with extrapyramidal symptoms as a side effect compared toHaloperidol.","['P28223', 'P14416', 'P08908', 'P35367', 'P21917', 'P35348', 'P35368', 'P25100']","Perospirone is a serotonin 5-HT2 receptor inverse agonist and dopamine D2 receptor antagonist based on receptor binding experiments3,4that binds to both receptors with high affinity. Perospirone is also a partial agonist at 5-HT1A receptors which are autoreceptors that stimulate the uptake of 5-HT and inhibit 5-HT release7. It also interacts with D4 receptors and α₁-adrenergic receptors as an antagonist, as well as histamine H1 receptor an inverse agonist. Binding to these receptors may explain sedative and hypotensive actions. Perospirone binds to D1 receptors with low affinity and minimal clinical significance4.",[H][C@@]12CCCC[C@]1([H])C(=O)N(CCCCN1CCN(CC1)C1=NSC3=CC=CC=C13)C2=O,"Antagonism at D receptors is believed to relieve the positive symptoms of schizophrenia such as delusions, hallucinations, and thought disorders. Perospirone targets the mesolimbic patway to reverse the overactivity of the dopaminergic signalling via D receptors. -HTA antagonism is thought to allevaite the negative symptoms and cognitive impairments of schizophrenia. These receptors are Gi/Go coupled receptors that lead to decreased neurotransmitter release and neuronal inhibition when activated, thus play a role in dopamine release regulation. Perospirone targets these receptors in the nigrostriatal pathway to reduce dopamine release and function. In contrast, -HTA receptor antagonism may improve the negative symptoms by enhancing dopamine and glutamate release in the mesocortical pathway. -HTA receptor activation further inhibits the release of -HT into the synaptic cleft.TargetActionsOrganismA-hydroxytryptamine receptor Ainverse agonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor Apartial agonistHumansUHistamine H receptorinverse agonistHumansUDopamine D receptorantagonistHumansUAlpha- adrenergic receptorsantagonistHumans",[],"['Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Neurotoxic agents', 'Psychotropic Drugs', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB00392,Profenamine,Profenamineis an antidyskinetic phenothiazine used to treat the symptoms of Parkinson's disease.,"['P11229', 'Q8TCU5', 'P08172']","Profenamine, a phenothiazine and antidyskinetic, is used in the treatment of Parkinson's disease. By improving muscle control and reducing stiffness, this drug permits more normal movements of the body as the disease symptoms are reduced. It is also used to control severe reactions to certain medicines such as reserpine, phenothiazines, chlorprothixene, thiothixene, loxapine, and haloperidol. Unlike other NMDA antagonists, profenamine — because of its anticholinergic action — is largely devoid of neurotoxic side effects. Profenamine also has a slight antihistaminic and local anesthetic effect.",CCN(CC)C(C)CN1C2=CC=CC=C2SC2=CC=CC=C12,"Profenamine's anti-Parkinson action can be attributed to its anticholinergic properties. Profenamine partially blocks central (striatal) cholinergic receptors, thereby helping to balance cholinergic and dopaminergic activity in the basal ganglia; salivation may be decreased, and smooth muscle may be relaxed. Drug-induced extrapyramidal symptoms and those due to parkinsonism may be relieved, but tardive dyskinesia is not alleviated and may be aggravated by anticholinergic effects. Profenamine's local anesthetic effect is due to its antagonism of the NMDA glutamate receptor. Glutamate is recognized as an important transmitter in nociceptive pathways, and the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, in particular, has been implicated in the mediation of neuropathic pain. Excessive release of glutamate at NMDA receptors on dorsal horn neurons of the spinal cord results in hyperactivation and hypersensitivity of these receptors (perceived as hyperalgesia), thought to be an integral feature of neuropathic pain.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAGlutamate receptor ionotropic, NMDA AantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'NMDA Receptor Antagonists', 'Sulfur Compounds', 'Tertiary Amines']" +DB01624,Zuclopenthixol,"Zuclopenthixolis an antipsychotic indicated for the management of schizophrenia. The acuphase formulation is indicated for initial treatment of acute psychosis or exacerbation of psychosis, while the depot formulation is best for maintenance.","['P21728', 'P21918', 'P14416', 'P35348', 'P08913', 'P28223', 'P35367']",Zuclopenthixol is a thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors.,OCCN1CCN(CC\C=C2\C3=C(SC4=C2C=C(Cl)C=C4)C=CC=C3)CC1,"Zuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene class. It mainly acts by antagonism of D and D dopamine receptors. Zuclopenthixol also has high affinity for alpha-adrenergic and -HT receptors. It has weaker histamine H receptor blocking activity, and even lower affinity for muscarinic cholinergic and alpha-adrenergic receptors.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansUHistamine H receptorantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thioxanthene Derivatives', 'Thioxanthenes', 'Tranquilizing Agents', 'Xanthenes']" +DB00810,Biperiden,Biperidenis a muscarinic receptor antagonist used to treat parkinsonism and control extrapyramidal side effects of neuroleptic drugs.,['P11229'],"Biperiden is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, biperiden possesses nicotinolytic activity. The parenteral form of biperiden is an effective and reliable agent for the treatment of acute episodes of extrapyramidal disturbances sometimes seen during treatment with neuroleptic agents. Akathisia, akinesia, dyskinetic tremors, rigor, oculogyric crisis, spasmodic torticollis, and profuse sweating are markedly reduced or eliminated. With parenteral biperiden, these drug-induced disturbances are rapidly brought under control.",OC(CCN1CCCCC1)(C1CC2CC1C=C2)C1=CC=CC=C1,"Parkinsonism is thought to result from an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the corpus striatum. The mechanism of action of centrally active anticholinergic drugs such as biperiden is considered to relate to competitive antagonism of acetylcholine at cholinergic receptors in the corpus striatum, which then restores the balance.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Bridged-Ring Compounds', 'Central Nervous System Agents', 'Cholinergic Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Piperidines', 'Tertiary Amines']" +DB00875,Flupentixol,Flupentixolis a thioxanthene neuroleptic used to treat schizophrenia and depression.,"['P14416', 'P21728', 'P28223', 'P35348', 'P35462', 'P21917', 'P28335', 'P11229']","Flupentixol is an antipsychotic agent with anxiolytic and mild sedative actions. It exerts weak anticholinergic and adrenergic effects. It possesses antiemetic actions. As flupentixol works by antagonizing dopamine actions, it can cause extrapyramidal effects,11mostly at doses greater than 10 mg. In clinical trials, flupentixol-induced extrapyramidal effects have been managed with anti-Parkinsonian drugs.3Drug esterification in the intramuscular formulation of the drug results in slow release of the drug from the injection site and a prolonged duration of action.11Flupentixol has been investigated for use in mild to moderate depression: compared to other antidepressant agents, flupentixol has a rapid onset of action, where antidepressive effects were observed within the first two to three days after administration.3As with other antipsychotic agents, flupentixol can cause QTc prolongation and increase the risk of arrhythmias. In clinical trials, flupentixol was associated with the risk of cardiovascular disease, cerebrovascular adverse events, stroke, and venous thromboembolism. Flupentixol can elevate the levels of prolactin; however, the clinical significance of hyperprolactinemia caused by neuroleptic drugs is unclear. Long-term hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone mineral density in both female and male subjects.11Interestingly, recent studies show that flupentixol exhibits anti-tumour properties alone or synergistically with other anticancer drugs like gefitinib. One study demonstrated thatin vitro, flupentixol docks to the ATP binding pocket of phosphatidylinositol 3-kinase (PI3K), a lipid kinase that activates signalling pathways that are often hyperactivated in some cancers. Flupentixol inhibited the PI3K/AKT pathway and survival of lung cancer cellsin vitroandin vivo.5",[H]\C(CCN1CCN(CCO)CC1)=C1/C2=CC=CC=C2SC2=C1C=C(C=C2)C(F)(F)F,"The mechanism of action of flupentixol is not completely understood. The antipsychotic actions are mainly thought to arise from cis(Z)-flupentixol, the active stereoisomer, acting as an antagonist at both dopamine Dand Dreceptors with equal affinities.Schizophrenia is a mental illness characterized by positive (such as hallucinations and delusions) and negative (such as affect flattening and apathy) symptoms. While several neurotransmitter systems are implicated in the pathophysiologic processes leading to the development of symptoms, the dopamine and glutamate systems have been extensively studied. It is generally understood that positive symptoms of schizophrenia arise from a dysregulated striatal dopamine pathway, leading to hyperstimulation of Dreceptors. Many antipsychotic agents work by blocking Dreceptors as antagonists;similarly, cis(Z)-flupentixol, the active stereoisomer, is an antagonist at Dreceptors.However, there is now evidence that antipsychotic agents can work by blocking other dopamine receptor subtypes, such as D, D, or Dreceptors.,,One study showed that cis(Z)-flupentixol is an antagonist at both dopamine Dand Dreceptors with equal affinities,and binds to D and D receptors with lower affinities. It also binds to alpha- adrenoceptors.Antidepressant effects of flupentixol are understood to be mediated by antagonism at -HTAreceptors, which are commonly downregulated following repeated antidepressant treatment.Flupentixol also binds to -HTCreceptors.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'P-glycoprotein inhibitors', 'Photosensitizing Agents', 'Piperazines', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thioxanthene Derivatives', 'Thioxanthenes', 'Tranquilizing Agents', 'Xanthenes']" +DB00737,Meclizine,"Meclizineis a histamine H1 antagonist used to treat nausea, vomiting, and dizziness associated with motion sickness.","['P35367', 'Q14994']","Meclizine works on the higher centres of the brain to reduce nausea, vomiting, or vertigo. It is effective against nausea and vomiting arising from many causes, including motion sickness and disorders affecting the vestibular system. The onset of action of meclizine is about 1 hour, with effects lasting between 8 to 24 hours.4Meclizine is reported to cause drowsiness due to its anticholinergic actions.5",CC1=CC(CN2CCN(CC2)C(C2=CC=CC=C2)C2=CC=C(Cl)C=C2)=CC=C1,"Vomiting is a centrally regulated reflex mechanism that initiates from the vomiting center and the chemoreceptor trigger zone (CTZ) located in the medulla. Motion sickness is also regulated by CTZ. The blood-brain barrier near the CTZ is relatively permeable to circulating mediators and CTZ can transmit impulses to vomiting center located in the brainstem. Different receptors responding to different factors, including histamine, -HT, enkephalins, substance P, and dopamine, are expressed along the brainstem to activate respective pathways and contribute to the control of vomiting. Histamine H receptors are expressed on the vestibular nuclei and nucleus of the solitary tract (NTS) that are activated by motion sickness and stimuli from the pharynx and stomach. When activated, H receptor signaling from these nuclei is transmitted to the CTZ and vomiting centre.Through its antagonistic action on the H receptors, meclizine primarily works by inhibiting signaling pathway transduction through histaminergic neurotransmission from the vestibular nuclei and NTS to the CTZ and medullary vomiting center.Meclizine may also decrease the labyrinth excitability and vestibular stimulation.TargetActionsOrganismAHistamine H receptorantagonistHumansUNuclear receptor subfamily group I member inverse agonistHumans",[],"['Anti-Allergic Agents', 'Anticholinergic Agents', 'Antiemetics', 'Antihistamines for Systemic Use', 'Antivertigo Preparations', 'Autonomic Agents', 'Benzene Derivatives', 'Benzhydryl Compounds', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinergic Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Emesis Suppression', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Piperazine Derivatives', 'Piperazines']" +DB01623,Thiothixene,Thiothixeneis an antipsychotic indicated for the management of schizophrenia.,"['P14416', 'P21728', 'P28223']","Thiothixene is an antipsychotic of the thioxanthene series. Navane possesses certain chemical and pharmacological similarities to the piperazine phenothiazines and differences from the aliphatic group of phenothiazines. Although widely used in the treatment of schizophrenia for several decades, thiothixene is seldom used today in favor of atypical antipsychotics such as risperidone.",CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3\C2=C\CCN2CCN(C)CC2)C=C1,"Thiothixene acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D, D, D and D - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (-HT and -HT, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha/alpha-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M/M-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thioxanthene Derivatives', 'Thioxanthenes', 'Tranquilizing Agents', 'Xanthenes']" +DB00621,Oxandrolone,Oxandroloneis an androgenic hormone used to treat muscle loss from prolonged corticosteroid treatment and to treat bone pain associated with osteoporosis.,['P10275'],"Oxandrolone is an anabolic steroids indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis. Anabolic steroids are synthetic derivatives of testosterone.",[H][C@@]12CC[C@](C)(O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])CC(=O)OC[C@]12C,Oxandrolones interact with androgen receptors in target tissues.TargetActionsOrganismAAndrogen receptoragonistHumans,['Weight Gain'],"['Alimentary Tract and Metabolism', 'Anabolic Agents', 'Anabolic Agents for Systemic Use', 'Anabolic Steroids', 'Androgens', 'Androstan Derivatives', 'Androstanes', 'Androstanols', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Steroids', 'Thyroxine-binding globulin inhibitors']" +DB00609,Ethionamide,Ethionamideis a second line antitubercular agent used to treat tuberculosis when other treatments have failed.,"['P9WGR1', 'P9WIE5']","Ethinamate is bacteriostatic againstM. tuberculosis. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturableMycobacterium tuberculosisorganisms from the lungs of H37Rv infected mice. Drug resistance developed with continued ethionamide monotherapy, but did not occur when mice received ethionamide in combination with streptomycin or isoniazid.",CCC1=NC=CC(=C1)C(N)=S,"Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Ethionamide, like prothionamide and pyrazinamide, is a nicotinic acid derivative related to isoniazid. It is thought that ethionamide undergoes intracellular modification and acts in a similar fashion to isoniazid. Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. Specifically isoniazid inhibits InhA, the enoyl reductase fromMycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.TargetActionsOrganismAEnoyl-[acyl-carrier-protein] reductase [NADH]inhibitorMycobacterium tuberculosisUCatalase-peroxidaseother/unknownMycobacterium tuberculosis",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Drugs causing inadvertant photosensitivity', 'Drugs for Treatment of Tuberculosis', 'Fatty Acid Synthesis Inhibitors', 'Hypolipidemic Agents', 'Isonicotinic Acids', 'Photosensitizing Agents', 'Pyridines', 'Thiocarbamide Derivatives']" +DB00726,Trimipramine,Trimipramineis a tricyclic antidepressant used to treat depression.,"['P31645', 'P23975', 'Q01959', 'P28223', 'P08908', 'P35348', 'P35368', 'P14416', 'P18089', 'P35367', 'P28335', 'P46098', 'P28221', 'P08913', 'P21728', 'P21918', 'P08588', 'P07550', 'P13945', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P08909']","Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.",CC(CN(C)C)CN1C2=CC=CC=C2CCC2=CC=CC=C12,Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (-HT).TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansASodium-dependent noradrenaline transporterinhibitorHumansUSodium-dependent dopamine transporterinhibitorHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor AantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUDopamine D receptorother/unknownHumansUAlpha-B adrenergic receptorother/unknownHumansUHistamine H receptorantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor AbinderHumansU-hydroxytryptamine receptor DbinderHumansUAlpha-A adrenergic receptorantagonistHumansUD() dopamine receptorbinderHumansUBeta adrenergic receptorbinderHumansUMuscarinic acetylcholine receptorbinderHumansU-hydroxytryptamine receptor CbinderRat,[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic Uptake Inhibitors', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Dibenzazepines', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists', 'Tertiary amine tricyclic antidepressants', 'Tricyclics and Other Norepinephrine-reuptake Inhibitors']" +DB01403,Methotrimeprazine,"Methotrimeprazineis a phenothiazine used in the management of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder.","['P14416', 'P21728', 'P21918', 'P35462', 'P21917', 'P28223', 'P28335', 'P35367', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Methotrimeprazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)",COC1=CC2=C(SC3=C(C=CC=C3)N2C[C@H](C)CN(C)C)C=C1,"Methotrimeprazine's antipsychotic effect is largely due to its antagonism of dopamine receptors in the brain. In addition, its binding to HT receptors may also play a role.TargetActionsOrganismADopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansUDopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor CantagonistHumansUHistamine H receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumans",['Perioperative analgesia'],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs causing inadvertant photosensitivity', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Hyperglycemia-Associated Agents', 'Muscarinic Antagonists', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenothiazines', 'Phenothiazines With Aliphatic Side-Chain', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB01171,Moclobemide,Moclobemideis a monoamine oxidase inhibitor used in the treatment of major depressive disorder and bipolar disorder.,"['P21397', 'P21397', 'P27338', 'P27338']","A selective, reversible inhibitor of monoamine oxidase (MAO) which increases the1. Besides its presence in sympathetic nerves, there is an abundant evidence that MAO-A is localized in noradrenergic neurons in the locus coeruleus and MAO-B is closely associated with serotonergic neurons of the raphe nucleus1.",ClC1=CC=C(C=C1)C(=O)NCCN1CCOCC1,"The mechanism of action of moclobemide involves the selective, reversible inhibition of MAO-A. This inhibition leads to a decrease in the metabolism and destruction of monoamines in the neurotransmitters. This results in an increase in the monoamines, relieving depressive symptoms,.TargetActionsOrganismAAmine oxidase [flavin-containing] AantagonistinhibitorHumansUMonoamine oxidaseantagonistHumansUAmine oxidase [flavin-containing] BantagonistHumans",[],"['Acids, Carbocyclic', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Amides', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Chlorobenzoates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Monoamine Oxidase A Inhibitors', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Nervous System', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB09185,Viloxazine,Viloxazineis a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults in children.,"['P23975', 'P41595', 'P28335', 'P35368', 'P07550', 'P35367', 'P25021', 'P11229', 'P08172', 'P20309', 'P08173', 'P21397', 'P27338']","Viloxazine is a serotonin-norepinephrine modulating agent that has been used as a treatment for depression and Attention Deficit Hyperactivity Disorder (ADHD).6Although it is not a stimulant agent, viloxazine produces amphetamine-like CNS stimulant effects without a risk for drug abuse or dependence.4Viloxazine does not produce sedative anticholinergic or adrenergic effects.1,4",CCOC1=CC=CC=C1OCC1CNCCO1,"Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children characterized by inattention and hyperactivity. In current literature, the pathophysiology of ADHD is understood to involve the imbalance of neurotransmitters, especially dopamine (DA) and norepinephrine (NE).The mechanism of action of viloxazine has not been fully elucidated; however, viloxazine is believed to work by modulating the monoaminergic neurotransmitter systems. Viloxazine is a selective and moderate norepinephrine reuptake inhibitor that binds to the norepinephrine transporter and inhibits the reuptake of norepinephrine.,It thereby increases extracellular norepinephrine levels across several brain regions.Viloxazine potentiates serotonergic effects: it was shown to enhance neuronal sensitivity to serotonin and increase serotonin levels in the brain.,In vitro, viloxazine is an antagonist at -HTBreceptors and an agonist -HTCreceptors.,-HTBreceptors expressed on GABAergic interneurons are involved in tonic inhibitory control of serotonin neurons that innervate the medial prefrontal context; thus, antagonism of -HTBreceptors may result in disinhibition and enhanced serotonin release in the brain region.There is conflicting evidence in the literature that viloxazine increases dopamine levels in the brain via direct or indirect effects. For example, the norepinephrine transporter is also involved in the reuptake of dopamine in the prefrontal cortexand stimulation of -HTCreceptors facilitates DA release and enhances dopaminergic transmission in the brain.As dopamine dysregulation in the prefrontal cortex and amygdala is implicated in ADHD pathophysiology, the impact of viloxazine on dopamine levels may contribute to its mechanism of action. However, there is insufficient evidence to conclude this. Viloxazine has a negligible impact on dopamine in the nucleus accumbens and is not associated with an abuse risk.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansA-hydroxytryptamine receptor BantagonistHumansA-hydroxytryptamine receptor CagonistHumansUAlpha-B adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumansUHistamine H receptorantagonistHumansUHistamine H receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUAmine oxidase [flavin-containing] AinhibitorHumansUAmine oxidase [flavin-containing] BinhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Adrenergic Uptake Inhibitors', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antidepressive Agents, Second-Generation', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H2 Antagonists', 'Histamine H3 Antagonists', 'MATE 1 Inhibitors', 'MATE inhibitors', 'Membrane Transport Modulators', 'Monoamine Oxidase A Inhibitors', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase B Inhibitors', 'Monoamine Oxidase Inhibitors', 'Morpholines', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Norepinephrine Reuptake Inhibitor', 'Norepinephrine Uptake Inhibitors', 'Oxazines', 'Psychoanaleptics', 'Psychotropic Drugs', 'UGT1A9 Substrates']" +DB00234,Reboxetine,Reboxetineis a drug used for the acute treatment of major depression and for maintenance therapy of depression.,['P23975'],"Reboxetine is a selective noradrenaline reuptake inhibitor (NaRI), the first drug of new antidepressant class. Reboxetine is an a-ariloxybenzyl derivative of morpholine. Reboxetine is primarily used to treat depression but has also been found useful in the treatment of narcolepsy and panic disorders.",[H][C@@]1(CNCCO1)[C@H](OC1=CC=CC=C1OCC)C1=CC=CC=C1,"Reboxetine is a selective inhibitor of noradrenaline reuptake. It inhibits noradrenaline reuptakein vitroto a similar extent to the tricyclic antidepressant desmethylimipramine. Reboxetine does not affect dopamine or serotonin reuptake and it has lowin vivoandin vitroaffinity for adrenergic, cholinergic, histaminergic, dopaminergic and serotonergic receptors.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumans",['Maintenances'],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Membrane Transport Modulators', 'Morpholines', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Oxazines', 'P-glycoprotein inhibitors', 'Psychoanaleptics', 'Psychotropic Drugs']" +DB00830,Phenmetrazine,A sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine.,"['P23975', 'Q01959']","Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden.",CC1NCCOC1C1=CC=CC=C1,"Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent dopamine transporterinhibitorHumans",[],"['Agents producing tachycardia', 'Agents that produce hypertension', 'Anti-Obesity Agents', 'Appetite Depressants', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Morpholines', 'Oxazines', 'Peripheral Nervous System Agents', 'Sympathomimetics']" +DB00535,Cefdinir,Cefdiniris a third generation cephalosporin used to treat susceptible Gram negative and Gram positive bacterial infections.,"['P08149', 'Q60FT7', 'P05164']","Cefdinir is a bactericidal agent that treats bacterial infections by interfering with cell wall synthesis.14Cefdinir exerts broad-spectrum activity against a variety of gram-positive and gram-negative bacterial infections. It is effective against several beta-lactamase enzyme producing bacteria. As a result, many organisms that are resistant to other cephalosporins may be susceptible to cefdinir.3,4,17",[H][C@]12SCC(C=C)=C(N1C(=O)[C@H]2NC(=O)C(=N/O)\C1=CSC(N)=N1)C(O)=O,"Five-member thiazolidine rings that make up penicillins are replaced in cephalosporins by a six-member dihydrothiazine ring, conferring greater bactericidal activity. This This -member ring enables cefdinir and other cephalosporins to resist inactivation by certain bacterial enzymes.With a mechanism similar to other beta-lactam antibiotics, the bactericidal activity of cefdinir is caused by the inhibition of cell wall synthesis via binding to penicillin-binding proteins (PBPs). Cefdinir, like other cephalosporins, penetrates the bacterial cell wall, combats inactivation by beta-lactamase enzymes, and inactivates penicillin-binding proteins.This interferes with the final step of transpeptidation in cell walls, eventually leading to cell lysis, which eventually leads to the death of bacteria that are susceptible to this drug.Cefdinir has shown affinity to penicillin protein binding proteins and .,,It has also been shown to inhibit transpeptidase enzymes of various bacteria, which may play a role in its bactericidal action.,One in vitro study suggests that cefdinir inhibits myeloperoxidase release extracellularly.The impact of this potential drug target in relation to its mechanism of action is unknown.TargetActionsOrganismAPenicillin-binding protein inhibitorNeisseria gonorrhoeaeAPBPinhibitorHaemophilus influenzaeNMyeloperoxidaseinhibitorHumansUPeptidoglycan transpeptidaseinhibitor",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Aza Compounds', 'Azabicyclo Compounds', 'beta Lactam Antibiotics', 'beta-Lactams', 'Cephalosporins', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Substrates', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00218,Moxifloxacin,Moxifloxacinis a fluoroquinolone antibiotic used to treat various bacterial infections.,"['P43700', 'P43702', 'P11388', 'P27169']","Moxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms:Corynebacteriumspecies,Micrococcus luteus,Staphylococcus aureus,Staphylococcus epidermidis,Staphylococcus haemolyticus,Staphylococcus hominis,Staphylococcus warneri,Streptococcus pneumoniae, andStreptococcus viridansgroup. Aerobic Gram-negative microorganisms:Acinetobacter lwoffii,Haemophilus influenzae, andHaemophilus parainfluenzae. Other microorganisms:Chlamydia trachomatis. Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.",[H][C@]12CN(C[C@@]1([H])NCCC2)C1=C(F)C=C2C(=O)C(=CN(C3CC3)C2=C1OC)C(O)=O,"The bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumansUSerum paraoxonase/arylesterase inhibitorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolone Antibacterial', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'Ophthalmologicals', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Sensory Organs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00207,Azithromycin,Azithromycinis a macrolide antibiotic used to treat a variety of bacterial infections.,['Q9UM07'],"Macrolides stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections4. +Azithromycin has additional immunomodulatory effects and has been used in chronic respiratory inflammatory diseases for this purpose3.",CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)CN(C)[C@H](C)[C@@H](O)[C@]1(C)O,"In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Azithromycin binds to the S rRNA of the bacterial S ribosomal subunit. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the S ribosomal subunitLabel,. This results in the control of various bacterial infections,Label. The strong affinity of macrolides, including azithromycin, for bacterial ribosomes, is consistent with their broad‐spectrum antibacterial activities.Azithromycin is highly stable at a low pH, giving it a longer serum half-life and increasing its concentrations in tissues compared to erythromycin.TargetActionsOrganismAS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaUProtein-arginine deiminase type-inhibitorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Experimental Unapproved Treatments for COVID-19', 'Lactones', 'Macrolide Antimicrobial', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'Moderate Risk QTc-Prolonging Agents', 'Ophthalmologicals', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Polyketides', 'QTc Prolonging Agents']" +DB08995,Diosmin,Diosminis a citrus flavonoid medication used to support vascular health.,['P35869'],"Diosmin is a venoactive drug supporting circulatory health through various actions on blood vessels; it supports lymphatic drainage and improves microcirculation while increasing venous tone and elasticity. For these reasons, diosmin is frequently taken by individuals with chronic venous disease to support vascular health and has been demonstrated to improve quality of life.3,17In addition to the above effects, diosmin exerts antioxidant activity and scavenges oxygen free radicals, reducing levels of oxidative stress normally detected through biomarkers such as prostaglandins isoprostane precursors.1In one clinical study, mean content of TNF alpha, VEGF-C, VEGF-A IL-6, in addition to FGF2 were decreased by after the therapy with diosmin; findings were statistically significant. Additionally, a decrease in edema and mean leg circumference of patients taking diosmin for three months was observed in a clinical study.3Diosmin has been demonstrated to enhance the metabolism of glucose in diabetic disorders.14",COC1=C(O)C=C(C=C1)C1=CC(=O)C2=C(O)C=C(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)C=C2O1,"Diosmin helps to maintain circulatory system structure and function, particularly vein strength and competence.The molecular mechanism of action of diosmin has not been established.Several resources indicate that diosmin binds to the aryl hydrocarbon receptor, however clinical relevance to vascular function is unknown.,,One study demonstrates that oral diosmin exerts effects on the in vitro metabolism of noradrenaline by varicose veins, potentially benefitting vascular health.TargetActionsOrganismUAryl hydrocarbon receptoragonistHumans",[],"['Benzopyrans', 'Capillary Stabilizing Agents', 'Chromones', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Flavones', 'Flavonoids', 'Heterocyclic Compounds, Fused-Ring', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'Pyrans', 'Vasoprotectives']" +DB00344,Protriptyline,Protriptylineis a tricyclic antidepressant that is indicated in the treatment of depression only under close clinical supervision.,"['P23975', 'P31645']","Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. The effectiveness of antidepressants appear after approximately two weeks following recommended adminsitration schedule. Gradual changes are thought to occur in the cerebral cortex and hippocampus, involved in emotion regulation as part of the limbic system, as receptor sensitivity is enhanced. While α1and β1receptors are sensitized, α2receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also reported to alter the perceptions of pain, including neuropathic or neuralgic pain, so they may exhibit analgesic properties. The mechanism of action behind this analgesic property is not fully understood; however, it is thought to involve modulation of endogenous opioid systems in the CNS via an indirect serotonergic route. Tricyclic antidepressants are also effective in relieving migraine prophylaxis, but not in abortion of acute migraine attack, potentially via their serotonergic effects.",CNCCCC1C2=CC=CC=C2C=CC2=CC=CC=C12,Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (-HT).TargetActionsOrganismASodium-dependent noradrenaline transporterinhibitorHumansASodium-dependent serotonin transporterinhibitorHumans,[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Antidepressive Agents, Tricyclic', 'Benzocycloheptenes', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Dibenzocycloheptenes', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Non-Selective Monoamine Reuptake Inhibitors', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01215,Estazolam,Estazolamis a benzodiazepine used for the short-term management of insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam.",ClC1=CC2=C(C=C1)N1C=NN=C1CN=C2C1=CC=CC=C1,"Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Anticonvulsants', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Photosensitizing Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents', 'Triazolobenzodiazepines']" +DB06756,Betaine,Betaineis a methyl group donor used for the treatment of homocystinuria to decrease elevated homocysteine blood levels.,['Q93088'],"Betaine decreases plasma homocysteine concentrations in homocystinuria cases caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl).5The decrease of homocysteine is estimated to be 20-30% of pre-treatment levels. Betaine supplementation in patients with homocystinuria also improves metabolic abnormalities in cerebrospinal fluid.6Reports have shown that depending on the type of homocystinuria, the therapeutic effectiveness of betaine alone may be limited, insufficient to decrease total homocysteine levels and prevent clinical symptoms. In patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency, betaine should be used when serum total homocysteine levels remain high despite dietary therapy.1Patients taking betaine for several years do not show evidence of tolerance. Also, betaine concentrations are not correlated with homocysteine concentrations.5In patients with MTHFR deficiency and cbl defects, betaine may increase methionine and S-adenosyl methionine (SAM) plasma levels. Patients with CBS deficiency without a dietary restriction of methionine may accumulate excessive amounts of methionine. Clinical data shows that in patients with CBS deficiency, increased plasma methionine levels were associated with cerebral edema.5,6",C[N+](C)(C)CC([O-])=O,"Homocystinuria is a hereditary disorder characterized by high levels of the amino acid homocysteine. This condition can be caused by deficiencies or defects in cystathionine beta-synthase (CBS), ,-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl).CBS converts homocysteine to cystathionine, and a deficiency in this enzyme can lead to an accumulation of homocysteine. MTHFR is responsible for producing -methyltetrahydrofolate, a methyl donor that participates in the conversion of homocysteine back to methionine; therefore, an MTHFR deficiency can also lead to homocystinuria.Additionally, a defect in cobalamin (vitamin B) cofactor metabolism can lead to homocystinuria, since a metabolite of cobalamin (methylcobalamin) promotes the conversion of homocysteine to methionine.Betaine transfers a methyl group via the enzyme betaine homocysteine methyl transferase (BHMT), converting homocysteine back into methionine and dimethylglycine (DMG).,In patients with homocystinuria, betaine reduces homocysteine levels and improves health outcomes.TargetActionsOrganismABetaine--homocysteine S-methyltransferase substrateHumans",[],"['Acid Preparations', 'Alimentary Tract and Metabolism', 'Amines', 'Amino Acids and Derivatives', 'Cholinesterase Inhibitors', 'Digestives, Incl. Enzymes', 'Gastrointestinal Agents', 'Lipid Regulating Agents', 'Lipotropic Agents', 'Methylating Activity', 'Methylating Agent', 'Onium Compounds', 'Other Miscellaneous Therapeutic Agents', 'Quaternary Ammonium Compounds', 'Trimethyl Ammonium Compounds']" +DB01428,Oxybenzone,Oxybenzoneis a sunscreen agent found in sunscreens that absorbs UV rays.,"['P06401', 'P10275', 'P03372', 'Q92731']",Oxybenzone is an organic compound used in sunscreens. It is a derivative of benzophenone.,COC1=CC(O)=C(C=C1)C(=O)C1=CC=CC=C1,"Oxybenzone absorbs UV-A ultraviolet rays, preventing them from reaching the skin.TargetActionsOrganismUProgesterone receptorantagonistHumansUAndrogen receptorantagonistHumansUEstrogen receptor alphaNot AvailableHumansUEstrogen receptor betaNot AvailableHumans",[],"['Benzene Derivatives', 'Compounds used in a research, industrial, or household setting', 'Cosmetics', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Ketones', 'Protective Agents', 'Radiation-Protective Agents', 'Sunscreen Agents']" +DB01419,Antrafenine,Antrafenine is a piperazine derivative drug that acts as an analgesic and anti-inflammatory drug with similar efficacy to naproxen. It is not widely used as it has largely been replaced by newer drugs.,"['P23219', 'P35354']","Its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.",FC(F)(F)C1=CC(=CC=C1)N1CCN(CCOC(=O)C2=CC=CC=C2NC2=C3C=CC(=CC3=NC=C2)C(F)(F)F)CC1,"Antrafenine is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-, generates prostaglandins involved in inflammation. Inhibition of COX- is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX- provides anti-inflammatory activity.TargetActionsOrganismUProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS']" +DB00179,Masoprocol,"A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils. [PubChem]","['P09917', 'P04278', 'Q96QT4']",Masoprocol is a novel antineoplastic agent. It is not known exactly how masoprocol works. Laboratory experiments have shown that masoprocol prevents cells similar to the ones found in actinic keratoses from multiplying. Masoprocol was withdrawn from the U.S. market in June 1996.,C[C@@H](CC1=CC(O)=C(O)C=C1)[C@H](C)CC1=CC(O)=C(O)C=C1,"Although the exact mechanism of action is not known, studies have shown that masoprocol is a potent -lipoxygenase inhibitor and has antiproliferative activity against keratinocytes in tissue culture, but the relationship between this activity and its effectiveness in actinic keratoses is unknown. Masoprocol also inhibits prostaglandins but the significance of this action is not yet known.TargetActionsOrganismAArachidonate -lipoxygenaseinhibitorHumansUSex hormone-binding globulinNot AvailableHumansATransient receptor potential cation channel subfamily M member inhibitorHumans",[],"['Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Antioxidants', 'Benzene Derivatives', 'Benzyl Compounds', 'Biological Factors', 'Catechols', 'Compounds used in a research, industrial, or household setting', 'Cyclooxygenase Inhibitors', 'Enzyme Inhibitors', 'Lignans', 'Lipoxygenase Inhibitors', 'Peripheral Nervous System Agents', 'Phenols', 'Protective Agents', 'Sensory System Agents']" +DB00429,Carboprost tromethamine,Carboprost tromethamineis a prostaglandin used to treat postpartum uterine hemorrhage due to atony when other methods of management have not been effective.,['P34995'],"Carboprost tromethamine administered intramuscularly stimulates in the gravid uterus myometrial contractions similar to labor contractions at the end of a full term pregnancy. Whether or not these contractions result from a direct effect of carboprost on the myome-trium has not been determined. Nonetheless, they evacuate the products of conception from the uterus in most cases. Postpartum, the resultant myometrial contractions provide hemostasis at the site of placentation. Carboprost tromethamine also stimulates the smooth muscle of the human gastrointestinal tract. This activity may produce the vomiting or diarrhea or both that is common when carbo-prost tromethamine is used to terminate pregnancy and for use postpartum. In laboratory animals and also in humans carboprost tromethamine can elevate body temperature. With the clinical doses of carboprost trometh-amine used for the termination of pregnancy, and for use postpartum, some patients do experience transient temperature increases. In laboratory animals and in humans large doses of carboprost tromethamine can raise blood pressure, probably by contracting the vascular smooth muscle. With the doses of carboprost tromethamine used for terminating pregnancy, this effect has not been clinically significant. In laboratory animals and also in humans carboprost tromethamine can elevate body temperature. With the clinical doses of carboprost tromethamine used for the termination of pregnancy, some patients do experience temperature increases. In some patients, carboprost tromethamine may cause transient bronchoconstriction.",NC(CO)(CO)CO.CCCCC[C@](C)(O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O,"Carboprost is a synthetic prostaglandin. It binds the prostaglandin E receptor, causing myometrial contractions, casuing the induction of labour or the expulsion of the placenta. Prostaglandins occur naturally in the body and act at several sites in the body including the womb (uterus). They act on the muscles of the womb, causing them to contract.TargetActionsOrganismAProstaglandin E receptor EP subtypeagonistHumans",['Pregnancy termination therapy'],"['Abortifacient Agents', 'Abortifacient Agents, Nonsteroidal', 'Alcohols', 'Autacoids', 'Biological Factors', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Genito Urinary System and Sex Hormones', 'Glycols', 'Inflammation Mediators', 'Lipids', 'Pharmaceutical Preparations', 'Propylene Glycols', 'Prostaglandins', 'Prostaglandins F, Synthetic', 'Prostaglandins, Synthetic', 'Reproductive Control Agents', 'Uterotonic agents']" +DB06196,Icatibant,Icatibantis a bradykinin B2 receptor antagonist used to treat acute episodes of swelling and inflammation associated with hereditary angioedema (HAE).,"['P30411', 'P15144']","Icatibant is a potent, specific, competitive, and selective peptidomimetic bradykinin beta2-receptor antagonist (pA2 = 9.04). It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. It also inhibits aminopeptidase N (Ki = 9.1 μM). If an IV dose of 0.4 and 0.8 mg/kg was infused over 4 hours, one may observe an inhibited response to bradykinin challenge for 6 - 8 hours following completion of infusion.",[H][C@]12C[C@]([H])(N(C(=O)[C@@]3([H])CC4=C(CN3C(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CS3)NC(=O)CNC(=O)[C@]3([H])C[C@@H](O)CN3C(=O)[C@@H]3CCCN3C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](N)CCCNC(N)=N)C=CC=C4)[C@@]1([H])CCCC2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O,"Bradykinin is a peptide-based hormone that is formed locally in tissues in response to a trauma and acts to increases vessel permeability, dilates blood vessels and causes smooth muscle cells to contract. Bradykinin plays an important role in the mediation of pain as surplus bradykinin is partly responsible for producing signs of inflammation by activating bradykinin B receptors. In patients with HAE, they have an absent or dysfunctional C-esterase inhibitor. This inhibitor is responsible for the production of bradykinin in which displacement of bradykinin from B receptors by icatibant has an inhibitory effect on the receptor for a relatively long time.TargetActionsOrganismAB bradykinin receptorantagonistHumansUAminopeptidase NinhibitorHumans",[],"['Agents causing angioedema', 'Amino Acids, Peptides, and Proteins', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Antirheumatic Agents', 'Autacoids', 'Biological Factors', 'Blood and Blood Forming Organs', 'Bradykinin B2 Receptor Antagonists', 'Bradykinin Receptor Antagonists', 'Complement Inactivating Agents', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Hereditary Angioedema', 'Immunologic Factors', 'Inflammation Mediators', 'Intercellular Signaling Peptides and Proteins', 'Kinins', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptides', 'Peripheral Nervous System Agents', 'Proteins', 'Sensory System Agents']" +DB01036,Tolterodine,"Tolterodineis a muscarinic receptor antagonist used to treat overactive bladder with urinary incontinence, urgency, and frequency.","['P20309', 'P08172', 'P08912', 'P11229', 'P08173']","Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function. The main effects of tolterodine are an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, consistent with an antimuscarinic action on the lower urinary tract.",CC(C)N(CC[C@H](C1=CC=CC=C1)C1=C(O)C=CC(C)=C1)C(C)C,"Both tolterodine and its active metabolite, -hydroxymethyltolterodine, act as competitive antagonists at muscarinic receptors. This antagonism results in inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anticholinergic Agents', 'Benzene Derivatives', 'Benzhydryl Compounds', 'Cholinergic Agents', 'Cresols', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Urinary Frequency and Incontinence', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Genitourinary Smooth Muscle Relaxants', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Phenols', 'Potential QTc-Prolonging Agents', 'Propanolamines', 'Propanols', 'QTc Prolonging Agents', 'Urological Agents', 'Urologicals']" +DB00170,Menadione,"A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.","['P38435', 'Q9BQB6', 'Q8N0U8', 'P00734', 'P00740', 'P04070', 'P07225', 'P16083', 'P15559', 'P02818']","Menadione (Vitamin K3) is a fat-soluble vitamin precursor that is converted into menaquinone in the liver. Vitamin K1 and K2 are the naturally occurring types of vitamin K. The former, which is also known as phylloquinone, is synthesized by plants and can be found in such foods as spinach, broccoli, lettuce, and soybeans. The latter, sometimes alternatively referred to as menaquinone, is primarily produced by bacteria in the anterior part of the gut and the intestines. Vitamin K3, on the other hand, is one of the many manmade versions of vitamin K. Also called menadione, this yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin inside of the animal body. While a vitamin K deficiency can be dangerous, especially to infants that may easily suffer from extensive hemorrhaging, an overdose can be as equally detrimental. Newborns that are administered too great a dosage of vitamin K3 can suffer from kernicterus, a form of severe brain damage that may produce decreased movement, loss of appetite, seizures, deafness, mental retardation, and even death. This condition is associated with an abnormally high concentration of bilirubin, a bile pigment, in the tissues of the brain, which can be caused by the presence of K3. For this reason, K3 is less often utilized medically than it was in former times.",CC1=CC(=O)C2=CC=CC=C2C1=O,"Menadione (vitamin K) is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein S serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone Ga (gamma-carboxyglutamate) protein or BGP, and the matrix Ga protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. The reduced form of vitamin K, vitamin K hydroquinone, is the actual cofactor for the gamma-carboxylases. Proteins containing gamma-carboxyglutamate are called Ga proteins.TargetActionsOrganismAVitamin K-dependent gamma-carboxylasecofactorHumansAVitamin K epoxide reductase complex subunit cofactorHumansAVitamin K epoxide reductase complex subunit -like protein cofactorHumansUProthrombinactivatorHumansUCoagulation factor IXactivatorHumansUVitamin K-dependent protein CactivatorHumansUVitamin K-dependent protein SactivatorHumansURibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHumansUNAD(P)H dehydrogenase [quinone] Not AvailableHumansUOsteocalcinagonistHumans",[],"['Antifibrinolytic Agents', 'Blood and Blood Forming Organs', 'Coagulants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Diet, Food, and Nutrition', 'Dietary Supplements', 'Diterpenes', 'Fibrin Modulating Agents', 'Food', 'Hematologic Agents', 'Hemostatics', 'Micronutrients', 'Naphthalenes', 'Naphthoquinones', 'Physiological Phenomena', 'Phytol', 'Quinones', 'Supplements', 'Terpenes', 'Vitamin K', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB12001,Abemaciclib,Abemaciclibis a medication used to treat HR+ HER2- advanced or metastatic breast cancer.,"['P11802', 'Q00534']","In combination with fulvestrant, the progression-free survival for patients with HR-positive, HER2-negative breast cancer was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant. As a monotherapy, 19.7% of patients taking abemaciclib achieved complete or partial shrinkage of their tumors for a median 8.6 months after treatment5. Abemaciclib induces cell cycle arrest and exerts an antitumor activity in human tumor xenograft models1.In patient investigations and a healthy volunteer study, abemaciclib is not shown to induce any clinically significant changes in the QTc intervalLabel.",CCN1CCN(CC2=CC=C(NC3=NC=C(F)C(=N3)C3=CC(F)=C4N=C(C)N(C(C)C)C4=C3)N=C2)CC1,"Regulation of cell cycle is crucial in maintaining proper cell growth; dysregulated cell cycle signalling pathway is a key component in inducing hyperproliferation of cells and tumor formation in various cancers. G to S phase cell cycle progression, or transition through the G restriction point (R), is promoted by the retinoblastoma tumor suppressor protein (Rb)-mediated pathway. Activation of Rb-mediated pathway requires the interaction of Cyclin-dependent kinases (CDK) and with D-type cyclins, which drives the formation of active CDK/CDK and subsequent phosphorylation of Rb,.Rb is a tumor suppressant protein that inhibits proliferation through binding to and suppressing the activity of the EF family of transcription factors. However, phosphorylation of Rb relieves suppression of EF to allow expression of genes required for passage through the restriction point. This leads to increased expression of downstream signalling molecules and activity of protein kinases that promote the cell cycle progression and initiation of DNA replication. Phosphorylation of Rb and other proteins by CDK/ additionally leads to transcription of genes involved in cell cycle-independent activities including signal transduction, DNA repair transcriptional control, and mRNA processing.Abemaciclib selectively inhibits CDK and CDK with low nanomolar potency, inhibits Rb phosphorylation resulting in a G arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells. Unlike other CDK inhibitors such asPalbociclibandRibociclib, abemaciclib exhibits greater selectivity for CDK compared to CDK.TargetActionsOrganismACyclin-dependent kinase inhibitorHumansACyclin-dependent kinase inhibitorHumans",[],"['Amines', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cyclin-dependent kinase (CDK) inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Kinase Inhibitor', 'MATE 1 Inhibitors', 'MATE 1 Substrates', 'MATE 1 Substrates with a Narrow Therapeutic Index', 'MATE 2 Inhibitors', 'MATE inhibitors', 'MATE substrates', 'Narrow Therapeutic Index Drugs', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Protein Kinase Inhibitors', 'Pyridines']" +DB01214,Metipranolol,Metipranololis a beta-adrenergic antagonist used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.,"['P08588', 'P07550']","Metipranolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Metipranolol is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Metipranolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Metipranolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce.",CC(C)NCC(O)COC1=C(C)C(C)=C(OC(C)=O)C(C)=C1,"Although it is known that metipranolol binds the beta and beta adrenergic receptors, the mechanism of metipranolol's action is not known. It has no significant intrinsic sympathomimetic activity, and has only weak local anesthetic (membrane-stabilizing) and myocardial depressant activity. It appears that the ophthalmic beta-adrenergic blocking agents reduce aqueous humor production, as demonstrated by tonography and fluorophotometry. A slight increase in aqueous humor outflow may be an additional mechanism.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Autonomic Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Non-Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'Sensory Organs', 'Sympatholytics']" +DB00805,Minaprine,"Minaprine is a psychotropic drug which has proved to be effective in the treatment of various depressive states. Like most antidepressants minaprine antagonizes behavioral despair. Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain.","['P21397', 'P41595', 'P28223', 'P28335', 'P22303', 'P31645', 'P21728', 'P14416', 'P11229']","Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. Similar to other antidepressant treatments, minaprine attenuates the beta-adrenergic receptor function. Studies have also shown that minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of minaprine on memory consolidation are related to its dopaminergic action.",CC1=CC(=NN=C1NCCN1CCOCC1)C1=CC=CC=C1,"Minaprine binds to serotonin type receptors and to dopamine D and D type receptors. It also binds to the serotonin reuptake pump. Therefore, minaprine blocks the reuptake of both dopamine and serotonin. It is also, to a slight degree, cholinomimetic. Thus it may exhibit both mood-brightening and nootropic properties. It also acts as a reversible inhibitor of MAO-A (RIMA).It has also been found to inhibit acetylcholinesterase.TargetActionsOrganismAAmine oxidase [flavin-containing] AinhibitorHumansA-hydroxytryptamine receptor BantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor CantagonistHumansAAcetylcholinesteraseinhibitorHumansUSodium-dependent serotonin transporterinhibitorHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansUMuscarinic acetylcholine receptor MagonistHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Central Nervous System Stimulants', 'Cholinesterase Inhibitors', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Nervous System', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB01010,Edrophonium,Edrophoniumis a cholinesterase inhibitor used to diagnose and evaluate myasthenia gravis.,"['P06276', 'P22303']","Edrophonium is a short and rapid-acting anticholinesterase drug. Its effect is manifest within 30 to 60 seconds after injection and lasts an average of 10 minutes. Edrophonium's pharmacologic action is due primarily to the inhibition or inactivation of acetylcholinesterase at sites of cholinergic transmission. Nicotinic acetylcholine (nAChR)receptors are found throughout the body, especially on muscle. Stimulation of these receptors causes to muscle contraction. In myasthenia gravis the body's immune system destroys many of the nicotinic acetylcholine receptors, so that the muscle becomes less responsive to nervous stimulation. Edrophonium chloride increases the amount of acetylcholine at the nerve endings. Increased levels of acetylcholine allow the remaining receptors to function more efficiently.",CC[N+](C)(C)C1=CC(O)=CC=C1,"Edrophonium works by prolonging the action acetylcholine, which is found naturally in the body. It does this by inhibiting the action of the enzyme acetylcholinesterase. Acetylcholine stimulates nicotinic and muscarinic receptors. When stimulated, these receptors have a range of effects.TargetActionsOrganismACholinesteraseinhibitorHumansAAcetylcholinesteraseinhibitorHumans",[],"['Amines', 'Antidotes', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Compounds used in a research, industrial, or household setting', 'Diagnostic Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Neurotransmitter Agents', 'Onium Compounds', 'Phenylammonium Compounds', 'Protective Agents', 'Quaternary Ammonium Compounds']" +DB09166,Etizolam,Etizolamis a thienodiazepine derivative used to treat anxiety and insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928', 'P25105']","Etizolam is a CNS depressant with anxiolytic, anticonvulsant, sedative-hypnotic and muscle relaxant effects. It acts on the benzodiazepine site of the GABA-A receptor as an agonist to increase inhibitory GABAergic transmission throughout the central nervous system. Studies indicate that etizolam mediates its pharmacological actions with 6 to 10 times more potency than that of diazepam. Clinical human studies performed in Italy showed clinical effectiveness of etizolam in relieving symptoms in patients with generalized anxiety disorders with depressive symptoms2,3,4. Etizolam also mediates imipramine-like neuropharmacological and behavioral effects, as well as minor effects on cognitive functioning. It is shown to substitute the actions of a short-acting barbiturate, pentobarbitol, in a drug discrimination study8. +Etizolam is an antagonist at platelet-activating-factor (PAF) receptor and attenuates the recurrence of chronic subdural hematoma after neurosurgery in clinical studies9. It is shown to inhibit PAF-induced bronchoconstriction and hypotension5.",CCC1=CC2=C(S1)N1C(C)=NN=C1CN=C2C1=CC=CC=C1Cl,"Etizolam is selectively a full agonist at GABA-A receptors to increase GABAergic transmission and enhance GABA-induced Cl- currents. It is reported to bind to the benzodiazepine binding site which is located across the interface between the alpha and gamma subunits. Benzodiazapines are reported to only bind to receptors that contain gamma and alpha /// subunits. Alpha--containing receptors mediate the sedative effects of etizolam whereas alpha- and alpha- subunit-containing receptors mediate the anxiolytic effect. Etizolam shows high potency and affinity towards GABA-A receptor with alpha beta gamma S subunit combination. By binding to the regulatory site of the receptor, etizolam potentiates GABA transmission by facilitating the opening of GABA-induced chloride channels. +Etizolam is a specific antagonist at PAFR. It inhibits PAF-induced platelet aggregation by inhibiting PAF binding to the receptors located on the surface of platelets with an IC of nM.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumansUPlatelet-activating factor receptorantagonistHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00266,Dicoumarol,"Dicoumarol is an oral anticoagulant agent that works by interfering with the metabolism of vitamin K. In addition to its clinical use, it is also used in biochemical experiments as an inhibitor of reductases.","['Q9BQB6', 'P15559', 'Q08257']","Dicumarol is an coumarin-like compound found in sweet clover. It is used as an oral anticoagulant and acts by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X).",OC1=C(CC2=C(O)C3=C(OC2=O)C=CC=C3)C(=O)OC2=C1C=CC=C2,"Dicumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.TargetActionsOrganismAVitamin K epoxide reductase complex subunit inhibitorHumansUNAD(P)H dehydrogenase [quinone] inhibitorHumansUQuinone oxidoreductaseinhibitorHumans",[],"['4-Hydroxycoumarins', 'Anticoagulants', 'Benzopyrans', 'Blood and Blood Forming Organs', 'Coumarins', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Fibrinolytic Agents', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Pyrans', 'Uncoupling Agents', 'Vitamin K Antagonists']" +DB01062,Oxybutynin,"Oxybutyninis an antimuscarinic agent that reduces detrusor muscle activity, relaxing the bladder and preventing the urge to void.","['P20309', 'P08172', 'P11229']","Oxybutynin exerts antispasmodic actions on the bladder, relieving the uncomfortable symptoms of overactive bladder, including urinary urgency and frequency. These actions occur through the inhibition of muscarinic receptors.A note on angioedema and anticholinergic effectsSymptoms of angioedema may occur with oxybutynin therapy. If angioedema is suspected, discontinue oxybutynin immediately and provide appropriate medical treatment.14In addition, anticholinergic effects may occur with the administration of this drug. Some symptoms may include hallucinations, confusion, agitation, and drowsiness. It is advisable to avoid operating heavy machinery before the response to oxybutynin has been monitored. Dose adjustments may be required.14",CCN(CC)CC#CCOC(=O)C(O)(C1CCCCC1)C1=CC=CC=C1,"Oxybutynin acts to relax the bladder by inhibiting the muscarinic action of acetylcholine on smooth muscle, and not skeletal muscle.The active of oxybutynin is metabolite is N-desethyloxybutynin. It competitively inhibits the postganglionic type , and muscarinic receptors. The above actions lead to increased urine capacity in the bladder, decreasing urinary urgency and frequency. In addition, oxybutynin delays the initial desire to void.,TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Acids, Carbocyclic', 'Agents producing tachycardia', 'Anticholinergic Agents', 'Autonomic Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Urinary Frequency and Incontinence', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Hydroxy Acids', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Urological Agents', 'Urologicals']" +DB04838,Cyclandelate,"Cyclandelateis a vasodilator used for the treatment of various blood vessel diseases, such as claudication and arteriosclerosis.","['P54289', 'P23141']","Cyclandelate is in a class of drugs called vasodilators. Cyclandelate relaxes veins and arteries, which makes them wider and allows blood to pass through them more easily.",CC1CC(CC(C)(C)C1)OC(=O)C(O)C1=CC=CC=C1,Cyclandelate produces peripheral vasodilation by a direct effect on vascular smooth muscle. Pharmacological action may be due to calcium-channel antagonism.TargetActionsOrganismUVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansULiver carboxylesterase Not AvailableHumans,[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Hydroxy Acids', 'Mandelic Acids', 'Peripheral Vasodilators', 'Vasodilating Agents']" +DB12328,Cantharidin,Cantharidinis a natured product indicated to treat molluscum contagiosum,['P35869'],"Cantharidin is a natural toxin produced by the blistering beetle that possesses both vesicant (blistering) and keratolytic effects.1,2The substance elicits these effects by inducing acantholysis (loss of intercellular connections) through the targeting of the desmosomal dense plaque, resulting in the detachment of the desmosomes from the tonofilaments.1,2Cantharidin's effectiveness against warts is proposed to be a result of the exfoliation of the wart body as a consequence of the compound's acantholytic action.11This acantholytic action generally does not go beyond the epidermal cells so that the basal layer remains intact and minimal effect occurs on the corium. There is consequently no scarring from the topical application of cantharidin.11",[H][C@]12CC[C@]([H])(O1)[C@]1(C)C(=O)OC(=O)[C@]21C,"Cantharidin is specifically absorbed by lipids in the membrane of epidermal keratinocytes, where it activates the release of neutral serine proteases.,These enzymes subsequently break the peptide bonds in surrounding proteins, leading to the progressive degeneration of desmosomal dense plaques, which are important cellular structures that participate in cell-to-cell adhesion.,Such degeneration results in the detachment of the tonofilaments that hold cells together. This process as a whole leads to selective acantholysis (loss of cellular connections) and blistering of the skin when the cantharidin topical application is applied upon specific topical developments like warts.,A blister(s) at the application site develops within to hours of application and typically resolves within to days.,Factors that can modify this proposed time frame include the volume or concentration of cantharidin used, physical contact time of the applied compound (usually between to hours), the presence of any occlusive dressings, or even patient sensitivity to cantharidin.,The blistered lesions ultimately heal without scarring.,Finally, there are some studies that suggest cantharidin's chemical profile as a potent and selective inhibitor of protein phosphatase A confers upon it an oxidative stress-independent growth inhibition of pancreatic cancer cells through cancer cell-cycle arrest and apoptosis.Nevertheless, the fact that little data regarding the pharmacodynamics and pharmacokinetics of cantharidin in the human body existsand certain toxic effects of cantharidin that have been observed following oral ingestion in humans like ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbanceare strong reasons as to why the compound currently lacks FDA approval is used fairly limitedly for formal therapeutic indications.TargetActionsOrganismUAryl hydrocarbon receptoragonistHumans",[],"['Benzofurans', 'Compounds used in a research, industrial, or household setting', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Irritants', 'Noxae', 'Toxic Actions']" +DB12442,Alvespimycin,"Alvespimycin is a derivative of geldanamycin and heat shock protein (HSP) 90 inhibitor. It has been used in trials studying the treatment of solid tumor in various cancer as an antitumor agent. In comparison to the first HSP90 inhibitor tanespimycin, it exhibits some pharmacologically desirable properties such as reduced metabolic liability, lower plasma protein binding, increased water solubility, higher oral bioavailability, reduced hepatotoxicity and superior antitumor activity1.",['P07900'],"Alvespimycin mediates an antitumor activity through HSP90 inhibition that targets client proteins for proteasomal destruction, including oncogenic kinases such as BRAF. The administration of the drug is shown to result in the depletion of client proteins that have oncogenic activity and potential induction of HSP70 (HSP72)1. It is more selective for tumors over normal tissue. A study also reports that alvespimycin enhances the potency of telomerase inhibition by imetelstat in pre-clinical models of human osteosarcoma3.",CO[C@H]1C[C@H](C)CC2=C(NCCN(C)C)C(=O)C=C(NC(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)C2=O,"Alvespimycin inhibits HSP and its regulation of correct folding and function of many cellular signalling proteins, which are referred to as Hsp client proteins. These client proteins are also referred to as oncoproteins and include Her-, EGFR, Akt, Raf-, p, Bcr-Abl, Cdk, Cdk and steroid receptors that are involved in cellular signalling pathways that drive cellular proliferation and counteract apoptosis. They are often over-expressed or mutated in tumors, and contribute to cancer progression and therapy resistance. Alvespimycin promotes an anticancer activity by disrupting Hsp's chaperone function and inducing the proteasomal degradation of oncoproteins. It is shown to reduce the levels of CDK and ERBB.TargetActionsOrganismAHeat shock protein HSP -alphainhibitorHumans",[],"['Amides', 'HSP90 Heat-Shock Proteins', 'Lactams', 'Quinones']" +DB00035,Desmopressin,Desmopressinis a synthetic analog of vasopressin used to reduce renal excretion of water in central diabetes insipidus and nocturia.,"['P30518', 'P37288', 'P47901']","By mimicking the actions of endogenous ADH, desmopressin acts as a selective agonist of V2 receptors expressed in the renal collecting duct (CD) to increase water re-absorption and reduce urine production. Desmopressin has been shown to be more potent than ADH in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I8. Desmopressin demonstrates markedly diminished pressor activity. Desmopressin administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection7.",NC(=O)CC[C@@H]1NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)CCSSC[C@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](CCCNC(N)=N)C(=O)NCC(N)=O,"Upon binding of desmopressin to V receptors in the basolateral membrane of the cells of the distal tubule and collecting ducts of the nephron, adenylyl cyclase is stimulated. The resulting intracellular cascades in the collecting duct lead to increased rate of insertion of water channels, called aquaporins, into the lumenal membrane and enhanced the permeability of the membrane to water.TargetActionsOrganismAVasopressin V receptoragonistHumansAVasopressin Va receptorNot AvailableHumansAVasopressin Vb receptorNot AvailableHumans",[],"['Agents that produce hypertension', 'Amino Acids, Peptides, and Proteins', 'Antidiuretic Agents', 'Arginine Vasopressin', 'Cardiovascular Agents', 'Coagulants', 'Drugs that are Mainly Renally Excreted', 'Factor VIII Activator', 'Hematologic Agents', 'Hemostatics', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Increased Coagulation Factor VIII Activity', 'Increased Coagulation Factor VIII Concentration', 'Natriuretic Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormones', 'Pituitary Hormones, Posterior', 'Posterior Pituitary Lobe Hormones', 'Proteins', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Vasopressin Analog', 'Vasopressin and Analogues', 'Vasopressins']" +DB13125,Lusutrombopag,Lusutrombopagis a medication used to treat thrombocytopenia in patients with chronic liver disease scheduled to have a procedure.,['P40238'],"The AUC of lusutrombopag was found to correlate the increased platelet counts. Following administration of 3 mg daily dose in patients with chronic liver disease and thrombocytopenia, the mean (standard deviation) maximum platelet count in patients (N=74) without platelet transfusion was 86.9 (27.2) × 10^9/L, and the median time to reach the maximum platelet count was 12.0 (5 to 35) daysLabel. Lusutrombopag was not shown to induce any clinically significant QTc prolongation at a dose 8 times the recommended dosageLabel.",CCCCCCO[C@@H](C)C1=C(OC)C(=CC=C1)C1=CSC(NC(=O)C2=CC(Cl)=C(\C=C(/C)C(O)=O)C(Cl)=C2)=N1,"Lusutrombopag mimics the biological actions of endogenous thrombopoietin (TPO) by acting as an agonist for the thrombopoietin receptor (TPOR) expressed on megakaryocytes. It binds to the transmembrane domain of the receptor and induces thrombocytopoiesis by targeting the same signal transduction system as that of endogenous TPO, which involves the activation of JAK and STAT pathways. It stimulates the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, which undergoes maturation to act as precursor cells for platelets. A single megakaryocyte produces and releases thousands of platelets upon maturation and series of remodeling events. Lusutrombopag displays high specificity towards human TPORs when compared to murine TPORs. Lusutrombopag may affect other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages. One case of increased leukocyte and erythrocyte counts that prolonged for over days was reported following administration in a patient with liver cirrhosis (LC) due to hepatitis C virus.TargetActionsOrganismAThrombopoietin receptoragonistHumans",[],"['Acids, Carbocyclic', 'BCRP/ABCG2 Substrates', 'Blood and Blood Forming Organs', 'Hemostatics', 'P-glycoprotein substrates', 'Sulfur Compounds', 'Thrombopoietin Receptor Agonist']" +DB00884,Risedronic acid,Risedronic acidis a bisphosphonate used to treat osteoporosis and Paget's disease.,['P14324'],Risedronate is a pyridine-based bisphosphonate that inhibits bone resorption caused by osteoclastsLabel.,OC(CC1=CN=CC=C1)(P(O)(O)=O)P(O)(O)=O,"Risedronatic acid binds to bone hydroxyapatiteLabel. Bone resorption causes local acidification, releasing risedronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing risedronic acid to the cytosol of osteoclasts where they induce apoptosis through inhbition of farnesyl pyrophosphate synthase. Inhibition of osteoclasts results in decreased bone resorption.TargetActionsOrganismAHydroxylapatiteantagonistHumansAFarnesyl pyrophosphate synthaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Bisphosphonates', 'Bone Density Conservation Agents', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Membrane Transport Modulators', 'Musculo-Skeletal System', 'Organophosphonates', 'Organophosphorus Compounds', 'Pyridines']" +DB06789,Hydroxyprogesterone caproate,Hydroxyprogesterone caproateis a synthetic progestin used for the prevention of spontaneous preterm births in singleton pregnancies in women who have previously had a spontaneous preterm birth.,['P06401'],"No specific pharmacodynamic studies have been performed to assess hydroxyprogesterone caproate injections. However, the mechanism of action is likely related to increased interaction between progesterone and progesterone receptors.",[H][C@@]12CC[C@](OC(=O)CCCCC)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The mechanism by which progesterone prevents preterm birth is not well understood, but many pathways are likely involved. Progesterone plays a vital role in regulation of the female reproductive system and is important for successful implantation of the embryo and maintenance of pregnancy. It acts by binding to progesterone receptors in the uterus, ovaries, breasts and in the central nervous system. These receptors exist in isoforms, PR-A and PR-B. Progesterone binding to these receptors ultimately leads to regulation of gene transcription. This results in an anti-inflammatory effect which blunts the proinflammatory state that occurs with initiation of labor, and maintains uterine queiscence by stabilizing progesterone acting on the myometrium.TargetActionsOrganismUProgesterone receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Antineoplastic Agents', 'Combination Contraceptives (with Estrogen and derivatives)', 'Contraceptive Agents, Female', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Estrogen Antagonists', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormone Antagonists', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydroxyprogesterones', 'Hyperglycemia-Associated Agents', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Progesterone and Derivatives', 'Progesterone Congeners', 'Progestin Contraceptives', 'Progestins', 'Steroids']" +DB06263,Amrubicin,"Amrubicin is a third-generation synthetic anthracycline currently in development for the treatment of small cell lung cancer. Pharmion licensed the rights to Amrubicin in November 2006. In 2002, Amrubicin was approved and launched for sale in Japan based on Phase 2 efficacy data in both SCLC and NSCLC. Since January 2005, Amrubicin has been marketed by Nippon Kayaku, a Japanese pharmaceutical firm focused on oncology, which licensed Japanese marketing rights from Dainippon Sumitomo, the original developer of Amrubicin13,15.",['P11388'],"Theanthracycline glycosidegroup of antibiotics, which includes amrubicin, represent a group of potent anticancer agents with potent activity against both solid tumors and hematological malignancies. They are the principal subjects of a large number of studies for the treatment of adult and childhood neoplastic diseases5.Amrubicin is a 9-aminoanthracycline derivative and promotes cell growth inhibition by stabilizing protein – DNA complexes followed by double-stranded DNA breaks, which are mediated by topoisomerase-II enzyme7.Anthracyclines have been observed to have a variety molecular effects (for example, DNA intercalation, inhibition of topoisomerase II, and stabilization of topoisomerase IIα cleavable complexes). Amrubicin shows decreased DNA intercalation when compared with doxorubicin. The decreased DNA interaction likely influences the intracellular distribution because amrubicin and its metabolite,amrubicinol. Amrubicin showed 20% distribution into the nucleus of P388 cells compared with the 80% nuclear distribution shown by doxorubicin (another anthracycline drug). The cell growth inhibitory effects of amrubicin appear to be mainly due to the inhibition of topoisomerase II11.",[H][C@@]1(C[C@@](N)(CC2=C1C(O)=C1C(=O)C3=CC=CC=C3C(=O)C1=C2O)C(C)=O)O[C@H]1C[C@H](O)[C@H](O)CO1,"As an anthracycline, amrubicin has antimitotic and cytotoxic activity through a variety of mechanisms of action. Amrubicin is found to form complexes with DNA via intercalation between base pairs, and it inhibits topoisomerase II enzyme activity by stabilizing the DNA-topoisomerase II complex, which prevents the re-ligation portion of the ligation-religation reaction that topoisomerase II normally catalyzes.Topoisomerase II is an enzyme located in the nucleus that regulates DNA structure through double-strand breakage and re-ligation, therefore modulating DNA replication and transcription. Inhibition of the enzyme leads to inhibition of DNA replication and halt cell growth with an arrest of the cell cycle occurring at the G/M phase. The mechanism by which amrubicin inhibits DNA topoisomerase II is believed to be through stabilization of the cleavable DNA–topo II complex, ending in re-ligation failure and DNA strand breakage,.DNA damage triggers activation of caspase- and - and cleavage of the enzyme PARP (Poly ADP ribose polymerase), leading to apoptosis and a loss of mitochondrial membrane potential. Amrubicin, like all anthracyclines, intercalates into DNA and produces reactive oxygen free radicals via interaction with NADPH, which causes cell damage.Compared with doxorubicin, another member of the anthracycline drug class, amrubicin binds DNA with a -fold lower affinity and therefore, higher concentrations of amrubicin are necessary to promote DNA unwinding.TargetActionsOrganismUDNA topoisomerase -alphaNot AvailableHumansUDNANot AvailableHumans",[],"['Anthracyclines and Related Substances', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cytotoxic Antibiotics and Related Substances', 'Glycosides', 'Naphthacenes']" +DB06693,Mevastatin,"Mevastatin or compactin is a cholesterol-lowering agent isolated fromPenicillium citinium. It was the first discovered agent belonging to the class of cholesterol-lowering medications known as statins. During a search for antibiotic compounds produced by fungi in 1971, Akira Endo at Sankyo Co. (Japan) discovered a class of compounds that appeared to lower plasma cholesterol levels. Two years later, the research group isolated a compound structurally similar to hydroxymethylglutarate (HMG) that inhibited the incorporation of acetate. The compound was proposed to bind to the reductase enzyme and was named compactin. Mevastatin is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the HMG-CoA substrate itself. Mevastatin is a pro-drug that is activated byin vivohydrolysis of the lactone ring. It has served as one of the lead compounds for the development of the synthetic compounds used today.",['P04035'],The primary cause of cardiovascular disease is atherosclerotic plaque formation. Mevastatin lowers hepatic production of cholesterol to reduce the risk of cardiovascular disease. Mevastatin competitively inhibits HMG-CoA reductase. This inhibition prevents the rate limiting step in cholesterol synthesis. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation.,[H][C@]12[C@H](CCC=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC,"Mevastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Mevastatin is a prodrug that is activatedin vivovia hydrolysis of the lactone ring. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with , times greater affinity than its natural substrate. The bicyclic portion of mevastatin binds to the coenzyme A portion of the active site.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Anti-Infective Agents', 'Anticholesteremic Agents', 'Antifungal Agents', 'Enzyme Inhibitors', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Regulating Agents', 'Naphthalenes']" +DB01588,Prazepam,Prazepamis a benzodiazepine used to manage more severe forms of anxiety disorders.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Prazepam is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant activity. Benzodiazepines may be habit-forming (causing mental or physical dependence), especially when taken for a long time or in high doses.",ClC1=CC2=C(C=C1)N(CC1CC1)C(=O)CN=C2C1=CC=CC=C1,"Prazepam is believed to stimulate GABA receptors in the ascending reticular activating system. Since GABA is inhibitory, receptor stimulation increases inhibition and blocks both cortical and limbic arousal following stimulation of the brain stem reticular formation.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Modulators', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00724,Imiquimod,"Imiquimodis a toll-like receptor 7 agonist used to treat non hyperkeratotic, non hypertrophic actinic keratosis, basal cell carcinoma, genital or perianal warts, and condyloma acuminata.","['Q9NYK1', 'Q9NR97']","Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratoses. Imiquimod can also be used to treat certain types of skin cancer called superficial basal cell carcinoma. Imiquimod is particularly useful on areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs.",CC(C)CN1C=NC2=C1C1=C(C=CC=C1)N=C2N,"Imiquimod's mechanism of action is via stimulation of innate and acquired immune responses, which ultimately leads to inflammatory cell infiltration within the field of drug application followed by apoptosis of diseased tissue. Imiquimod does not have direct antiviral activity. Studies of mice show that imiquimod may induce cytokines, including interferon-alpha (IFNA) as well as several IFNA genes (IFNA, IFNA, IFNA, IFNA, and IFNA) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-, IL-, and tumor necrosis factor alpha genes. In the treatment of basal cell carcinoma, Imiquimod appears to act as a toll-like receptor- agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. In treating basal cell carcinoma it may increase the infiltration of lymphocytes, dendritic cells, and macrophages into the tumor lesion.TargetActionsOrganismAToll-like receptor agonistHumansUToll-like receptor agonistHumans",[],"['Adjuvants, Immunologic', 'Aminoquinolines', 'Antineoplastic Agents', 'Cancer immunotherapy', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Heterocyclic Compounds, Fused-Ring', 'Immune Response Modifiers', 'Immunologic Factors', 'Immunomodulatory Agents', 'Immunosuppressive Agents', 'Immunotherapy', 'Increased Cytokine Activity', 'Increased Cytokine Production', 'Interferon Inducers', 'Misc. Skin and Mucous Membrane Agents', 'Quinolines', 'Toll-Like Receptor Agonists']" +DB06707,Levonordefrin,Levonordefrinis a topical sympathomimetic amine found in local anesthetic products that is used for nasal decongestion or vasoconstriction during dental procedures.,"['P08913', 'P18089', 'P18825']","Levonordefrin is a sympathomimetic amine used as a vasoconstrictor in local anesthetic solutions. It has pharmacologic activity similar to that of Epinephrine but it is more stable than Epinephrine. In equal concentrations, Levonordefrin is less potent than Epinephrine in raising blood pressure, and as a vasoconstrictor.",C[C@H](N)[C@H](O)C1=CC(O)=C(O)C=C1,"It is designed to mimic the molecular shape of adrenaline. It binds to alpha-adrenergic receptors in the nasal mucosa. Here it can, therefore, cause vasoconstriction.TargetActionsOrganismAAlpha- adrenergic receptorsagonistHumans",[],"['Adrenergic Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Benzene Derivatives', 'Cardiovascular Agents', 'Catecholamines', 'Catechols', 'Epinephrine and similars', 'Phenols', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB08868,Fingolimod,Fingolimodis a sphingosine 1-phosphate receptor modulator used to treat patients with the relapsing-remitting form of multiple sclerosis (MS) and studied to manage lung complications of COVID-19.,"['Q9H228', 'P21453', 'Q99500', 'Q13547', 'O95977']","In multiple sclerosis, fingolimod binds to sphingosine receptors, reducing its associated neuroinflammation.12In COVID-19, it may reduce lung inflammation and improve the clinical outcomes of patients with this disease.13Fingolimod causes a transient reduction in heart rate and AV conduction during treatment initiation. It has the potential to prolong the QT interval.13",CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1,"Sphingosine‐‐phosphate (SP) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as SP–R. SP and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous systems.,SP can be expressed ubiquitously, playing an important role in regulating inflammation. SPR, SPR, and SPR receptors can be found in the cardiovascular, immune, and central nervous systems. SPR is found on lymphocytic and hematopoietic cells, while SPR expression is found only on the spleen (on natural killer cells) or in the central nervous system.The active form of the drug, fingolimod phosphate, is a sphingosine -phosphate receptor modulator that exerts its mechanism of action in MS by binding to various sphingosine -phosphate receptors (, , , and ). It suppresses the exit of lymphocytes from lymph nodes, leading to a lower level of lymphocytes circulating in the peripheral circulation. This reduces the inflammation that is associated with MS. The mechanism of action of fingolimod is not fully understood but may be related to reduced lymphocyte circulation into the central nervous system.,Immune modulating treatment such as fingolimod is not typically employed for SARS-CoV- pneumonia. Despite this, with the tissue findings of pulmonary edema and hyaline membrane formation, the timely use of immune modulators such as fingolimod can be considered to prevent acute respiratory distress syndrome (ARDS) associated with COVID-.TargetActionsOrganismASphingosine -phosphate receptor modulatorHumansASphingosine -phosphate receptor modulatorHumansASphingosine -phosphate receptor modulatorHumansUHistone deacetylase inhibitorHumansUSphingosine -phosphate receptor modulatorHumans",['Alternative Treatment'],"['Alcohols', 'Amines', 'Amino Alcohols', 'Antineoplastic and Immunomodulating Agents', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Substrates', 'Experimental Unapproved Treatments for COVID-19', 'Glycols', 'Immunologic Factors', 'Immunomodulatory Agents', 'Immunosuppressive Agents', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'Propylene Glycols', 'Selective Immunosuppressants', 'Sphingosine 1 Phosphate Receptor Modulators', 'Sphingosine 1-phosphate Receptor Modulator']" +DB09477,Enalaprilat,Enalaprilatis an antihypertensive agent used for the management of hypertension when oral therapy is not practical.,"['P12821', 'P46663']","Enalaprilat injection results in the reduction of both supine and standing systolic and diastolic blood pressure, usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients. The onset of action usually occurs within fifteen minutes of administration with the maximum effect occurring within one to four hours. The abrupt withdrawal of enalaprilat has not been associated with a rapid increase in blood pressure. +The duration of hemodynamic effects appears to be dose-related. However, for the recommended dose, the duration of action in most patients is approximately six hours. +Following administration of enalapril, there is an increase in renal blood flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with renovascular hypertension.",[H][C@@](C)(N[C@@]([H])(CCC1=CC=CC=C1)C(O)=O)C(=O)N1CCC[C@@]1([H])C(O)=O,"Enalaprilat is the active metabolite of the orally available pro-drug, enalapril. Used in the treatment of hypertension, enalapril is an ACE inhibitor that prevents Angiotensin Converting Enzyme (ACE) from transforming angiotensin I into angiotensin II. As angiotensin II is responsible for vasoconstriction and sodium reabsorption in the proximal tubule of the kidney, down-regulation of this protein results in reduced blood pressure and blood fluid volumeTargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumansUB bradykinin receptorNot AvailableHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Amino Acids, Peptides, and Proteins', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Decreased Blood Pressure', 'Dipeptides', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Oligopeptides', 'Peptides', 'Photosensitizing Agents', 'Protease Inhibitors']" +DB01246,Alimemazine,"Alimemazineis an antihistamine agent used to prevent and relieve allergic conditions which cause pruritus and other allergic skin conditions, including urticaria.",['P35367'],"Trimeprazine (also known as Alimemazine) is a tricyclic antihistamine, similar in structure to the phenothiazine antipsychotics, but differing in the ring-substitution and chain characteristics. Trimeprazine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, trimeprazine is not used clinically as an anti-psychotic. It acts as an anti-histamine, a sedative, and an anti-emetic (anti-nausea). Trimeprazine is used principally as an anti-emetic, to prevent motion sickness or as an anti-histamine in combination with other medications in cough and cold preparations. Tricyclic antihistamines are also structurally-related to the tricyclic antidepressants, explaining the antihistaminergic adverse effects of these two drug classes and also the poor tolerability profile of tricyclic H1-antihistamines.",CC(CN(C)C)CN1C2=CC=CC=C2SC2=CC=CC=C12,"Trimeprazine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Antihistamines for Systemic Use', 'Antipruritics', 'Antipsychotic Agents', 'Central Nervous System Depressants', 'Dermatologicals', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Phenothiazine Derivatives', 'Phenothiazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfur Compounds']" +DB00723,Methoxamine,Methoxamineis an alpha adrenergic agonist used to treat hypotension.,"['P35348', 'P25100', 'P35368']","Methoxamine is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Methoxamine is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Methoxamine acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels.",COC1=CC(C(O)C(C)N)=C(OC)C=C1,"Methoxamine acts through peripheral vasoconstriction by acting as a pure alpha- adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic and diastolic).TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansUAlpha-D adrenergic receptorbinderHumansUAlpha-B adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alcohols', 'Amines', 'Amino Alcohols', 'Autonomic Agents', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Cardiovascular Agents', 'Ethylamines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Phenethylamines', 'Propanolamines', 'Propanols', 'Sympathomimetics', 'Vasoconstrictor Agents']" +DB01210,Levobunolol,Levobunololis a beta-adrenergic antagonist used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.,"['P08588', 'P07550']","Levobunolol is an ophthalmic beta-blocker, equally effective at β(1)- and β(2)-receptor sites. Levobunolol reduces both elevated and normal IOP in patients with or without glaucoma. In patients with elevated IOP, levobunolol reduces mean IOP by approximately 25-40% from baseline. As the drug is a nonselective &beta-adrenergic blocking agent, it can produce both systemic pulmonary and cardiovascular effects following topical application to the eye. These effects include adverse pulmonary effects (eg. bronchoconstriction, increased airway resistance), and a decrease in blood pressure and heart rate.",CC(C)(C)NC[C@H](O)COC1=CC=CC2=C1CCCC2=O,"Levobunolol's mechanism of action in reducing IOP is not clearly defined, but is believed to be due to a reduction of the production of aqueous humor via blockage of endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiglaucoma Preparations and Miotics', 'Autonomic Agents', 'Beta-adrenergic Agents', 'Bradycardia-Causing Agents', 'Bunolol', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Hypotensive Agents', 'Naphthalenes', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'Sensory Organs', 'Sympatholytics', 'Tetrahydronaphthalenes']" +DB06711,Naphazoline,"Naphazolineis a sympathomimetic vasoconstrictor used for the symptomatic relief of redness and itching of the eye, and nasal congestion.","['P08913', 'P35348']","Naphazoline is a sympathomimetic alpha adrenergic agonist that acts to vasoconstrict nasal or ocular arterioles, resulting in reduced congestion at the site of administration6,7.",C(C1=NCCN1)C1=CC=CC2=CC=CC=C12,"Naphazoline is a vasoconstrictor that functions by stimulating alpha adrenergic receptors in arterioles leading to decreased congestion at the site of administration.Naphazoline causes the release of norepinephrine in sympathetic nerves. Norepinephrine binds to alpha adrenergic receptors and causes vasoconstriction. Naphazoline is also a mild beta adrenergic receptor agonist, which can cause rebound vasodilation after the alpha adrenergic stimulation has ended. Naphazoline's release of norepinephrine also triggers a negative feedback loop which decreases production of norepinephrine, which can lead to rhinitis medicamentosa after long term use when naphazoline is stopped.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumans",['Ocular vasoconstriction therapy'],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Cardiovascular Agents', 'Decongestants and Antiallergics', 'Imidazoles', 'Nasal Decongestants', 'Nasal Preparations', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Respiratory System Agents', 'Sensory Organs', 'Sympathomimetics', 'Sympathomimetics Used as Decongestants', 'Sympathomimetics, Plain', 'Vasoconstrictor Agents']" +DB00527,Cinchocaine,Cinchocaineis an anesthetic used for local or regional anesthesia.,"['Q14524', 'Q9Y5Y9', 'P0DP23']","Dibucaine is an amide-type local anesthetic, similar to lidocaine.",CCCCOC1=NC2=CC=CC=C2C(=C1)C(=O)NCCN(CC)CC,"Local anesthetics block both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions through sodium channel inhibition. This reversibly stabilizes the membrane and inhibits depolarization, resulting in the failure of a propagated action potential and subsequent conduction blockade.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansASodium channel protein type subunit alphainhibitorHumansUCalmodulininhibitorHumans",[],"['Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Amides', 'Analgesics and Anesthetics', 'Anesthetics', 'Anesthetics for Topical Use', 'Anesthetics, Local', 'Antipruritics and Local Anesthetics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Cell-mediated Immunity', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Dermatologicals', 'Heterocyclic Compounds, Fused-Ring', 'Increased Histamine Release', 'Local Anesthetics (Amide)', 'Nervous System', 'Ophthalmologicals', 'Otologicals', 'Peripheral Nervous System Agents', 'Quinolines', 'Sensory Organs', 'Sensory System Agents', 'Standardized Chemical Allergen', 'Vasoprotectives']" +DB04948,Lofexidine,Lofexidineis a centrally acting alpha2-adrenergic agonist used for the symptomatic treatment of acute opioid withdrawal syndrome to facilitate abrupt opioid discontinuation in adults.,"['P08913', 'P35348', 'P08908', 'P34969', 'P28335', 'P28221']","In clinical trials, lofexidine presented more severe opioid withdrawal effects than observed with methadone. On the other hand, in clinical trials of methadone withdrawal, lofexidine effectively reduced withdrawal symptoms, especially hypotension.5The clinical reports have also indicated that lofexidine presents a better outcome when used briefly.6In phase 3 clinical trials, lofexidine was shown to generate a significantly higher completion rate of opioid discontinuation. Some pharmacological studies were performed and there were no off-target effects reported.9",CC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1,"Lofexidine is a potent alpha-adrenergic receptor agonist with some moderate agonistic affinity towards Alpha-A adrenergic receptor and -HTa, -HT, HTc and HTd receptors.The alpha-adrenergic receptor is normally targeted by norepinephrine and its activation inhibits the synthesis of cAMP which in turn leads to potassium efflux and suppression of neural firing and inhibition of norepinephrine release. All of this activity can reduce the heart rate, blood pressure, and attenuate sympathetic stress response.Opioids inhibit cAMP in the noradrenergic neurons and their discontinuation produces a rise in the level of cAMP. This will generate an increase in norepinephrine which is associated with the symptoms of withdrawal. The magnitude of the effect is augmented by chronic opioid use due to the compensatory mechanisms of continuous negative feedback. Therefore, chronic opioid use translates into an exacerbated production of cAMP and norepinephrine release.Lofexidine replaces the opioid-driven inhibition of cAMP production by activating the alpha-adrenergic receptor and moderating the symptoms of opioid withdrawal. This effect is performed without interacting with opioid receptors which mediate other activities of opioid dependence or addiction.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansNAlpha-A adrenergic receptoragonistHumansN-hydroxytryptamine receptor AagonistHumansN-hydroxytryptamine receptor agonistHumansN-hydroxytryptamine receptor CagonistHumansN-hydroxytryptamine receptor DagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Central alpha-2 Adrenergic Agonist', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Addictive Disorders', 'Drugs Used in Opioid Dependence', 'Hypotensive Agents', 'Imidazoles', 'Imidazolines', 'MATE 1 Inhibitors', 'MATE inhibitors', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'QTc Prolonging Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists']" +DB08838,Agmatine,"Agmantine is a natural metabolite of the amino acid arginine. It is formed when arginine is decarboxylated by the enzyme arginine decarboxylase and is found naturally in ragweed pollen, ergot fungi, octopus muscle, herring sperm, sponges, and the mammalian brain. Agmatine is both an experimental and investigational drug. As an investigational drug, it is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy between the ages of 18 to 75 years. Up to now (July 2013), the results of this study have not yet been published. As an experimental drug, agmatine is being studied for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). The exact mechanism of action is still being investigated for all of the potential indications of agmatine.","['P18825', 'Q9Y2I1', 'P02708', 'Q05586', 'P48048', 'Q00975', 'Q9UHC3']","Agmatine has several physiological effects. Its cardiovascular effects include mildly reducing heart rate and blood pressure. Also it promotes a mild hypoglycemic state, reduces cellular oxidative stress, and enhances glomerular filtration rate.",NCCCCNC(N)=N,"The exact mechanism of action is still being investigated for all of the potential indications of agmatine. Some of the biochemical mechanisms discovered so far concern agmatine's indication for diabetes, neuroprotection, and psychiatric conditions. In diabetes, agmatine produces hypoglycemia by increasing the release of insulin form pancreatic islet cells and increasing glucose uptake by the cells through increased endorphin release from the adrenal glands. Concerning neuroprotection, agmatine's effects are thought to involve modulation of receptors (NMDA, alpha , and imidazoline) and ion channels (ATP sensitive potassium channels and voltage-gated calcium channels) as well as blocking nitric oxide synthesis. Agmatine blocks nitric oxide synthesis by reducing the nitric oxide synthase - (NOS-) protein in astroglial cells and macrophages. With respect to agmatine's benefit in psychiatric disorders, it is suggested that the mechanism involves neurotransmitter receptor modulation of the NMDA, alpha-, serotonin, opioid, and imidazoline receptors. Specifically when agmatine binds to the imidazoline and alpha receptors, it acts as a neurotransmitter and releases catecholamines from the adrenal gland.TargetActionsOrganismAAlpha-C adrenergic receptoragonistHumansANischarinagonistHumansAAcetylcholine receptor subunit alphaantagonistHumansAGlutamate receptor ionotropic, NMDA antagonistHumansAATP-sensitive inward rectifier potassium channel antagonistHumansAVoltage-dependent N-type calcium channel subunit alpha-BantagonistHumansAAcid-sensing ion channel agonistHumans",[],"['Agents causing hyperkalemia', 'Amidines', 'Antiarrhythmic agents', 'Anticholinergic Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Guanidines', 'Nicotinic Antagonists', 'NMDA Receptor Antagonists', 'OCT1 substrates', 'OCT2 Substrates', 'Vasodilating Agents']" +DB04861,Nebivolol,Nebivololis a beta blocking agent used to treat hypertension and aid in the management of heart failure.,"['P08588', 'P07550', 'P13945']","Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function.2,3It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily.2,9Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease.9Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.9",OC(CNCC(O)C1CCC2=C(O1)C=CC(F)=C2)C1CCC2=C(O1)C=CC(F)=C2,"Nebivolol is a highly selective beta- adrenergic receptor antagonistwith weak beta- adrenergic receptor antagonist activity.Blocking beta- adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure.,,,The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity.Nebivolol also inhibits aldosterone, and beta- antagonism in the juxtaglomerular apparatus also inhibits the release of renin.Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction.l-nebivolol is responsible for beta- adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output.,,,,The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzopyrans', 'Beta blocking agents and calcium channel blockers', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Selective', 'Beta Blocking Agents, Selective, and Thiazides', 'Beta-Blockers (Beta1 Selective)', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Ethanolamines', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Pyrans', 'Vasodilating Agents']" +DB00953,Rizatriptan,Rizatriptanis a triptan used to treat migraines with or without aura.,"['P28222', 'P28221', 'P08908', 'P28566', 'P30939', 'P34969']","Rizatriptan relieves migraine-associated symptoms.1,5,9Rizatriptan is reported to reach the maximum plasma concentrations more quickly and produces a more rapid onset of pain relief than other triptans, such assumatriptan;2,3,5however, it has a relatively shorter elimination half-life than other triptans.5Rizatriptan causes transient increases in blood pressure to some extent.1In vitro, rizatriptan was shown to contract isolated human coronary arteries; however, since the EC50for this effect is high, rizatriptan is not expected to cause myocardial ischemia at therapeutic plasma concentrations in patients with normal coronary circulation.3Rizatriptan has a weak affinity for other 5-HT1 receptor subtypes (5-HT1A, 5-HT1E, 5-HT1F) and the 5-HT7receptor but has no significant activity at 5-HT2, 5-HT3, alpha- and beta-adrenergic, dopaminergic, histaminergic, muscarinic or benzodiazepine receptors.12",CN(C)CCC1=CNC2=C1C=C(CN1C=NC=N1)C=C2,"There are several physiological and molecular processes implicated in the pathophysiology of migraine. Vasodilation of intracranial extracerebral blood vessels, particularly those supplying the dura mater, has been associated with migraine pain.,Activation of the trigeminovascular system leads to the release of vasoactive neuropeptides (such as substance P, calcitonin gene-related peptide (CGRP), and neurokinin A) from the trigeminal nerve innervating the intracranial vessels and dura mater. Vasoactive neuropeptides cause perivascular inflammation and vasodilation in the periphery. Migraine-associated nausea and vomiting are thought to arise from the activation of central and nociceptive sensory neurons that project to autonomic brain-stem nuclei and higher subcortical and cortical pain processing centres.An imbalance in serotonin (-HT) levels has also been documented: -HT binds to -HTBand -HTDreceptors to promote trigeminal neuronal firing and vasoconstriction.,Rizatriptan is a selective agonist at the -HTBand -HTDreceptors on intracranial blood vessels and sensory nerves of the trigeminal system. It binds to these receptors with high affinity.The exact mechanism of action of rizatriptan has not been fully elucidated; however, several documented pharmacological actions of rizatriptan may contribute to its antimigraine effects. Rizatriptan causes vasoconstriction of intracranial extracerebral blood vessels, which is thought to occur primarily via -HTBreceptors. Rizatriptan also inhibits nociceptive neurotransmission in trigeminal pain pathways. It attenuates the release of vasoactive neuropeptides by the trigeminal nerve, which is thought to occur via neurogenic and central -HTDreceptors.,,Rizatriptan inhibited neurogenic dural vasodilation and plasma protein extravasation in animal studies.,,,TargetActionsOrganismA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor DagonistHumansU-hydroxytryptamine receptor AagonistHumansU-hydroxytryptamine receptor EagonistHumansU-hydroxytryptamine receptor FagonistHumansU-hydroxytryptamine receptor agonistHumans",['Acute Treatment of Migraine'],"['Agents that produce hypertension', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Biogenic Amines', 'Biogenic Monoamines', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Migraine Disorders', 'Monoamine Oxidase A Substrates', 'Nervous System', 'Neurotransmitter Agents', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Triptans']" +DB00964,Apraclonidine,Apraclonidineis an alpha adrenergic agonist used to treat raised intraocular pressure.,"['P35348', 'P08913', 'P18089']",Apraclonidine significantly lowers intraocular pressure with minimal effects on cardiovascular and pulmonary parameters. It lowers intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow.,NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1,"Apraclonidine is a relatively selective alpha adrenergic receptor agonist that stimulates alpha receptors to a lesser extent. It has a peak ocular hypotensive effect occurring at two hours post-dosing. The exact mechanism of action is unknown, but fluorophotometric studies in animals and humans suggest that Apraclonidine has a dual mechanism of action by reducing aqueous humor production through the constriction of afferent ciliary process vessels, and increasing uveoscleral outflow.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansUAlpha-B adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Antiglaucoma Preparations and Miotics', 'EENT Drugs, Miscellaneous', 'Hypotensive Agents', 'Imidazoles', 'Imidazolines', 'Neurotransmitter Agents', 'Ophthalmics', 'Ophthalmologicals', 'Sensory Organs', 'Sympathomimetics in Glaucoma Therapy']" +DB00670,Pirenzepine,"Pirenzepineis an antimuscarinic agent used to treat peptic ulcers, gastric ulcers, and duodenal ulcers.",['P11229'],"Pirenzepine belongs to a group of medications called antispasmodics/anticholinergics. These medications are used to relieve cramps or spasms of the stomach, intestines, and bladder. Pirenzepine is used to treat duodenal or stomach ulcers or intestine problems. It can be used together with antacids or other medicine in the treatment of peptic ulcer. It may also be used to prevent nausea, vomiting, and motion sickness.",CN1CCN(CC(=O)N2C3=CC=CC=C3C(=O)NC3=C2N=CC=C3)CC1,"Pirenzepine is a muscarinic receptor antagonist and binds to the muscarinic acetylcholine receptor. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Anticholinergic Agents', 'Benzazepines', 'Benzodiazepinones', 'Cholinergic Agents', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Neurotransmitter Agents']" +DB01170,Guanethidine,"Guanethidineis an antihypertensive agent used in the management of moderate and severe hypertension, either alone or as an adjunct, and for the management of renal hypertension.",['P23975'],"High blood pressure can cause the heart and arteries to not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanethidine works by decreasing the heart rate and relaxing the blood vessels so that blood can flow more easily through the body, thereby reducing these risks. It is a postganglionic sympathetic nerve terminal blocker that prevents the release of norepinephrine from nerve terminals.",NC(N)=NCCN1CCCCCCC1,"Guanethidine acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine (NE), rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters to be concentrated within the transmitter vesicles in place of NE, leading to gradual depletion of NE stores in the nerve endings. Guanethidine at the nerve terminal blocks the release of noradrenaline in response to an action potential. In contrast to ganglionic blocking agents, Guanethidine suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, Guanethidine lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.TargetActionsOrganismASodium-dependent noradrenaline transporterinducerHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Amidines', 'Antiadrenergic Agents, Peripherally Acting', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Autonomic Agents', 'Cardiovascular Agents', 'Catecholamine-depleting Sympatholytic', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Acidifying Agents', 'Guanidine Derivatives', 'Guanidine Derivatives and Diuretics', 'Guanidines', 'Neurotransmitter Agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Sensory Organs', 'Sympatholytics']" +DB01192,Oxymorphone,Oxymorphoneis an opioid analgesic used in the management of moderate-to-severe pain and for analgesic therapies.,"['P35372', 'P41143']",Oxymorphone is a semi-synthetic opioid substitute for morphine. It is a potent analgesic. Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. Opioids produce respiratory depression by direct action on brain stem respiratory centers. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.,[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1(O)CCC2=O,"Oxymorphone interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. Also, it has been shown that oxymorphone binds to and inhibits GABA inhibitory interneurons via mu-receptors. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.TargetActionsOrganismAMu-type opioid receptoragonistHumansUDelta-type opioid receptorantagonistHumans","['Perioperative analgesia', 'Obstetrical analgesia therapy']","['Adjuvants', 'Adjuvants, Anesthesia', 'Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'High-risk opioids', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Natural Opium Alkaloids', 'Nervous System', 'Opiate Agonists', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00067,Vasopressin,Vasopressinis a peptide hormone used to increase blood pressure in patients with vasodilatory shock who are resistant to fluid and catecholamine therapy.,"['P30518', 'P37288', 'P47901', 'P30559']","Vasopressin is a nonapeptide antidiuretic hormone involved in modulating various physiological processes, including autonomic signalling, stress response, behaviour, and memory; the most well-known modulation is of blood pressure.1,2,3,4,10Vasopressin acts both within the brain and in the periphery to modulate blood pressure through sympathetic outflow, baroreflex modulation, vasoconstriction, and renal fluid retention.6,7,8These mechanisms vary by location and physiological state, leading to occasionally contradictory responses to vasopressin. Although generally safe, vasopressin may worsen cardiac output in patients with impaired cardiac function. The cessation of vasopressin therapy may result in transient reversible diabetes insipidus, which may require additional desmopressin or vasopressin to manage.10",NCCCCC(NC(=O)C1CCCN1C(=O)C1CSSCC(N)C(=O)NC(CC2=CC=C(O)C=C2)C(=O)NC(CC2=CC=CC=C2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(N)=O)C(=O)N1)C(=O)NCC(N)=O.NC1CSSCC(NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC2=CC=C(O)C=C2)NC1=O)C(=O)N1CCCC1C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O,"Vasopressin, Cyclo (-) L-Cysteinyl-L-Tyrosyl-L-PhenylalanylL-Glutaminyl-L-Asparaginyl-L-Cysteinyl-L-Prolyl-L-Arginyl-L-Glycinamide, is a cyclic nonapeptide hormone primarily produced by the supraoptic and periventricular nuclei of the hypothalamus.,Vasopressin release is mediated by sensory pathways, in which either a % increase in plasma osmolarity or a % decrease in blood pressure causes the release of endogenous vasopressin.Upon release, vasopressin mediates a variety of physiological effects, both centrally and systemically, primarily by binding to G-protein-coupled receptors termed V(VA), V, and V(VB).Vreceptors are abundantly expressed in the brain whereby vasopressin binding can increase blood pressure through autonomic pathways.Peripherally, Vis localized in the blood vessels (vascular smooth muscle), platelets, adrenal glands, kidneys, and liver.,Vasopressin binding to Vcauses hydrolysis of phosphatidylinositol-,-bisphosphate into inositol triphosphate (IP) and diacylglycerol (DAG) by phospholipase C, which in turn release intracellular calcium and activate protein kinase C (PKC) to open voltage-gated calcium channels (VGCCs) while closing potassium channels. Overall, intracellular calcium levels rise, which bind calmodulin and cause muscular contraction, resulting in vasoconstriction.This is balanced by the apparent ability of vasopressin to induce vasodilation through binding oxytocin receptors and activating endothelial nitric oxide (NO) synthase; NO acts antagonistically to reduce muscle contraction.It is also thought that vasopressin, acting through both Vand oxytocin receptors, causes the cardiac release of atrial natriuretic peptide (ANP), which has a negative inotropic effect; indeed, vasopressin tends to decrease heart rate and cardiac output, although the opposite effect has been noted with low doses.,Vreceptors are abundantly expressed in the distal convoluted tubules and the collecting ducts of the kidneys.,Vasopressin binding to Vcauses activation of a Gsprotein that subsequently activates protein kinase A (PKA) through adenylyl cyclase-mediated increase in cyclic adenosine monophosphate (cAMP), which leads to phosphorylation of the water channel aquaporin- (AQP) and its trafficking to the cell surface.,Increased AQP levels lead to increased water reabsorption and explains vasopressin's antidiuretic effects.V(formerly VB) receptors are primarily located in the anterior pituitary and brain.,Vasopressin released during acute stress causes adrenocorticotropic hormone (ACTH) release from the pituitary through Vand by potentiating the effects of corticotrophin-releasing factor. Within the brain itself, Vactivation modulates various effects, including recognition, memory, aggression, anxiety, and depression.Thus, vasopressin can affect a wide variety of physiological processes, often in apparently contradictory ways depending on the patient's dose and physiological state. Vasodilatory shock causes an immediate release of vasopressin from to times its normal serum concentration, which falls again to normal levels in prolonged shock; in this context, normal serum levels are insufficient to control the pathologic vasodilation.,In these cases, vasopressin acts to depolarize hyperpolarized vascular smooth muscle cells, restore sensitivity to catecholamines, and inhibit excessive nitric oxide production, primarily through acting through Vreceptors. Therefore, vasopressin helps decrease the dose requirement for norepinephrine and is routinely administered together with norepinephrine to restore normal blood pressure in shock states.,TargetActionsOrganismAVasopressin V receptoragonistregulatorHumansAVasopressin Va receptoragonistregulatorHumansAVasopressin Vb receptoragonistHumansAOxytocin receptoragonistHumans",['Dental Local Anesthesia'],"['Amino Acids, Peptides, and Proteins', 'Antidiuretic Agents', 'Arginine Vasopressin', 'Arginine Vasopressin, analogs & derivatives', 'Cardiovascular Agents', 'Coagulants', 'Decreased Diuresis', 'Hematologic Agents', 'Hemostatics', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Natriuretic Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary', 'Pituitary Hormones', 'Pituitary Hormones, Posterior', 'Proteins', 'Vasoconstriction', 'Vasoconstrictor Agents', 'Vasopressin and Analogues', 'Vasopressins']" +DB00756,Hexachlorophene,Hexachloropheneis a chlorinated bisphenol antiseptic used as a surgical scrub and skin cleanser.,"['P06149', 'O14521', 'P00367', 'P03372']","Hexachlorophene, a detergent cleanser, is an antibacterial sudsing emulsion for topical administration. It is a bacteriostatic cleansing agent. It cleanses the skin thoroughly and has bacteriostatic action against staphylococci and other gram-positive bacteria. Cumulative antibacterial action develops with repeated use. Cleansing with alcohol or soaps containing alcohol removes the antibacterial residue.",OC1=C(CC2=C(O)C(Cl)=CC(Cl)=C2Cl)C(Cl)=C(Cl)C=C1Cl,"The primary mechanism of action of hexachlorophene, based on studies withBacillus megatherium, is to inhibit the membrane-bound part of the electron transport chain, respiratory D-lactate dehydrogenase. It induces leakage, causes protoplast lysis, and inhibits respiration.TargetActionsOrganismAD-lactate dehydrogenaseinhibitorEscherichia coli (strain K)ASuccinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrialinhibitorHumansUGlutamate dehydrogenase , mitochondrialinhibitorHumansUEstrogen receptor alphaNot AvailableHumans","['Antibiotic pre-surgical prophylaxis', 'Bacteriostatic skin cleanser']","['Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Antiseptics and Disinfectants', 'Benzene Derivatives', 'Chlorobenzenes', 'Chlorophenols', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Phenol and Derivatives', 'Phenols', 'Photosensitizing Agents']" +DB01004,Ganciclovir,Gancicloviris a DNA polymerase inhibitor used to treat cytomegalovirus and herpetic keratitis of the eye.,"['P04293', 'Q9QNF7']","Ganciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses bothin vitroandin vivo. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells.",NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1,"Ganciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes.In vitro, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-ADNAincorporation into and destabilizationHumansAThymidine kinasesubstrateHHV-",[],"['Agents Causing Muscle Toxicity', 'Agents that reduce seizure threshold', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytomegalovirus Nucleoside Analog DNA Polymerase Inhibitor', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Ganciclovir and prodrug', 'Heterocyclic Compounds, Fused-Ring', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'Nucleic Acid Synthesis Inhibitors', 'Nucleoside Analog Antiviral', 'Nucleosides and Nucleotides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OCT1 inhibitors', 'OCT1 substrates', 'Ophthalmologicals', 'Purines', 'Purinones', 'Sensory Organs']" +DB01605,Pivmecillinam,"Pivmecillinamis a prodrug of the beta lactam antibiotic mecillinam, indicated for the treatment of uncomplicated urinary tract infections (UTIs).",['Q8XJ01'],"Pivmecillinam is a pivaloyloxymethyl ester of amdinocillin that is well absorbed orally, but broken down to amdinocillin in the intestinal mucosa. It is active against gram-negative organisms and used as for amdinocillin.",[H]C(=N[C@@H]1C(=O)N2[C@@H](C(=O)OCOC(=O)C(C)(C)C)C(C)(C)S[C@]12[H])N1CCCCCC1,Pivmecillinam interferes with the biosynthesis of the bacterial cell wall however its activity is slightly different from that of other penicillins and cephalosporinsTargetActionsOrganismAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A),[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00132,Linolenic acid,Linolenic acidis a polyunsaturated omega-3 fatty acid found in many supplements.,"['O60427', 'O95864', 'Q8NER1', 'Q07869', 'Q96RI1', 'Q03181', 'P37231', 'P19793', 'Q9NXB9', 'Q9NYP7', 'P32418']","Alpha Linolenic Acid (ALA) is an 18-carbon polyunsaturated fatty acid with three double bonds. It is also called an omega-3 fatty acid, and is essential for all mammals. Alpha-linolenic acid (or omega 3 fatty acid) intake can decrease the risk of cardiovascular diseases by 1) preventing arrhythmias that can lead to sudden cardiac death, 2) decreasing the risk of thrombosis (blood clot formation) that can lead to heart attack or stroke, 3) decreasing serum triglyceride levels, 4) slowing the growth of atherosclerotic plaque, 5) improving vascular endothelial function, 6) lowering blood pressure slightly, and 7) decreasing inflammation. ALA deficiencies can lead to visual problems and sensory neuropathy. Scaly and hemorrhagic skin or scalp inflammations may also develop.",CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O,"Alpha Linolenic Acid or ALA is considered an essential fatty acid because it is required for human health, but cannot be synthesized by humans. It is in fact a plant-derived fatty acid. Humans can synthesize other omega- fatty acids from ALA, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor of the series- prostaglandins, the series- leukotrienes and the series- thromboxanes. These eicosanoids have anti-inflammatory and anti-atherogenic properties. ALA metabolites may also inhibit the production of the pro-inflammatory eicosanoids, prostaglandin E (PGE) and leukotriene B (LTB), as well as the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin- beta (IL- beta). Omega- fatty acids like ALA and its byproducts can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation. They regulate gene expression through their effects on the activity of transcription factors including NF-kappa B and members of the peroxisome proliferator-activated receptor (PPAR) family. Incorporation of ALA and its metabolites in cell membranes can affect membrane fluidity and may play a role in anti-inflammatory activity, inhibition of platelet aggregation and possibly in anti-proliferative actions of ALA. ALA is first metabolized by delta desaturease into steridonic acid.TargetActionsOrganismAFatty acid desaturase ligandHumansAFatty acid desaturase ligandHumansATransient receptor potential cation channel subfamily V member inhibitorHumansUPeroxisome proliferator-activated receptor alphaNot AvailableHumansUBile acid receptoragonistHumansUPeroxisome proliferator-activated receptor deltaNot AvailableHumansUPeroxisome proliferator-activated receptor gammaNot AvailableHumansURetinoic acid receptor RXR-alphaNot AvailableHumansUElongation of very long chain fatty acids protein substrateHumansUElongation of very long chain fatty acids protein substrateHumansUSodium/calcium exchanger Not AvailableHumans",['Nutritional supplementation'],"['Dietary Fats', 'Dietary Fats, Unsaturated', 'Dietary Supplements', 'Fats', 'Fatty Acids', 'Fatty Acids, Essential', 'Fatty Acids, Omega-3', 'Fatty Acids, Unsaturated', 'Linolenic Acids', 'Lipids', 'Supplements']" +DB08799,Antazoline,Antazolineis an antihistamine agent used for the symptomatic treatment of nasal congestion and allergic conjunctivitis.,['P35367'],"Antazoline is a histamine H1 receptor antagonist. It selectively bind to but does not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine.",C(N(CC1=CC=CC=C1)C1=CC=CC=C1)C1=NCCN1,"Antazoline binds to the histamine H receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Anti-Allergic Agents', 'Antiallergic Agents, Excl. Corticosteroids', 'Antihistamines for Systemic Use', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Imidazoles', 'Moderate Risk QTc-Prolonging Agents', 'Nasal Preparations', 'Neurotransmitter Agents', 'QTc Prolonging Agents']" +DB08834,Tauroursodeoxycholic acid,Tauroursodeoxycholic acidis the taurine conjugate of ursodeoxycholic acid with antiapoptotic and ER stress response dampening effects used in some countries to treat gallstones. It is also being investigated for a wide variety of other conditions.,['P08648'],"Tauroursodeoxycholic acid works to decrease bile acid1and cholesterol levels.4It reduces the cholesterol content and increases the bile acid content in gallbladder bile to prevent the formation of cholesterol gallstones.4Tauroursodeoxycholic acid possesses anti-apoptotic and anti-inflammatory properties. These findings provoked the investigations of tauroursodeoxycholic acid as a potential therapeutic agent for neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease.2Other studies also suggest that tauroursodeoxycholic acid can promote angiogenesis and suppress adipogenesis of adipose-derived mesenchymal stem cells (MSCs). Anti-osteoporotic effects of tauroursodeoxycholic acid have also been documented, as it was shown to enhance osteogenic differentiation of bone marrow-derived MSCs.3",[H][C@@]12CC[C@H]([C@H](C)CCC(=O)NCCS(O)(=O)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@H](O)C[C@]2([H])C[C@H](O)CC[C@]12C,"About % of gallstones are formed by cholesterol, which may be caused by altered gut microbiota from a high-fat diet and other factors. The gut microbiota regulates bile acid metabolism; thus, altered composition in gut microbiota may significantly change the bile acid pool and alter cholesterol secretion.While the exact mechanism of action of tauroursodeoxycholic acid in reducing and preventing gallstone formation is unclear, tauroursodeoxycholic acid may achieve this effect in a number of ways. A recent mouse study suggests that tauroursodeoxycholic acid inhibits intestinal cholesterol absorption and lowers liver cholesterol levels by upregulating the bile acid excretion from the liver to the gallbladder. Tauroursodeoxycholic acid lowers the bile cholesterol saturation in the gallbladder, thereby increasing the solubility of cholesterol in bile. It can also maintain a specific gut microbiota composition to promote the synthesis of bile acids and reduce liver inflammation caused by the lipopolysaccharide in the blood. Ultimately, tauroursodeoxycholic acid enhances the synthesis of bile acids in the liver and reduces cholesterol in the serum and liver.Tauroursodeoxycholic acid inhibits cell apoptosis by disrupting the mitochondrial pathway of cell death. It works by inhibiting oxygen-radical production, ameliorating endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response. Other anti-apoptotic processes mediated by tauroursodeoxycholic acid include cytochrome c release, caspase activation, DNA and nuclear fragmentation, and inhibition of p transactivation. It is believed that tauroursodeoxycholic acid works on multiple cellular targets to inhibit apoptosis and upregulate survival pathways.TargetActionsOrganismUIntegrin alpha-activatorHumans",[],"['Bile Acids and Salts', 'Cholagogues and Choleretics', 'Cholanes', 'Cholic Acids', 'Gastrointestinal Agents', 'Isomerism', 'Sulfur Compounds', 'Taurodeoxycholic Acid']" +DB06204,Tapentadol,"Tapentadolis an opioid used to manage severe pain that has not responded to non-opioid medications, and for which opioid analgesic therapy is appropriate.","['P35372', 'P23975', 'P41145', 'P41143', 'P31645']","Tapentadol is an opioid agonist that exerts physiological effects commonly caused by the opioid drug class. These effects include miosis, reduced gastrointestinal motility, and peripheral vasodilation. Tapentadol produces respiratory depression by reducing the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.5Tapentadol has a high potential for misuse and abuse, which can lead to the development of substance use disorder. Abuse of tapentadol poses a risk of overdose and death, which increases with alcohol or other central nervous system depressants.5",CC[C@H]([C@@H](C)CN(C)C)C1=CC(O)=CC=C1,"Tapentadol is a centrally-acting synthetic analgesic. Although their clinical relevance is unclear, tapentadol is believed to have two main mechanisms of action.Tapentadol is a selective mu-opioid receptor (MOR) agonist: it binds to MOR with an affinity greater than or equal to ten-fold affinity compared to delta- and kappa-opioid receptors.Tapentadol also inhibits noradrenaline reuptake, thereby increasing noradrenaline levels and activating alpha- receptors to promote analgesia.,Tapentadol is a weak serotonin reuptake inhibitor; however, this action does not contribute to its analgesic effect.TargetActionsOrganismUMu-type opioid receptoragonistHumansUSodium-dependent noradrenaline transporterinhibitorHumansUKappa-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansUSodium-dependent serotonin transporterinhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Uptake Inhibitors', 'Analgesics', 'Antidepressive Agents', 'Benzene Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Membrane Transport Modulators', 'Narcotics', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Opiate Agonists', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Phenols', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB01614,Acepromazine,"Acepromazine is one of the phenothiazine derivative psychotropic drugs, used little in humans, however frequently in animals as a sedative and antiemetic.","['P14416', 'P21728', 'P28223', 'P08908', 'P35348', 'P35368']",Acepromazine is one of the phenothiazine derivative psychotropic drugs. Acepromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Acepromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.,CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(C=C2)C(C)=O,"Acepromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D, D, D and D - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (-HT and -HT, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha/alpha-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M/M-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor AantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Phenothiazines', 'Phenothiazines With Aliphatic Side-Chain', 'Psycholeptics', 'Psychotropic Drugs', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Tranquilizing Agents']" +DB00733,Pralidoxime,Pralidoximeis a cholinesterase reactivator used to treat organophosphate poisoning.,"['P22303', 'P06276']","Pralidoxime is to reactivate cholinesterase (mainly outside of the central nervous system) which has been inactivated by phosphorylation due to an organophosphate pesticide or related compound. The destruction of accumulated acetylcholine can then proceed, and neuromuscular junctions will again function normally. Pralidoxime also slows the process of ""aging"" of phosphorylated cholinesterase to a nonreactivatable form, and detoxifies certain organophosphates by direct chemical reaction. The drug has its most critical effect in relieving paralysis of the muscles of respiration. Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is always required concomitantly to block the effect of accumulated acetylcholine at this site. Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc., but this action is relatively unimportant since atropine is adequate for this purpose.",C[N+]1=C(\C=N\O)C=CC=C1,"Pralidoxime is an antidote to organophosphate pesticides and chemicals. Organophosphates bind to the esteratic site of acetylcholinesterase, which results initially in reversible inactivation of the enzyme. Acetylcholinesterase inhibition causes acetylcholine to accumulate in synapses, producing continuous stimulation of cholinergic fibers throughout the nervous systems. If given within hours after organophosphate exposure, pralidoxime reactivates the acetylcholinesterase by cleaving the phosphate-ester bond formed between the organophosphate and acetylcholinesterase.TargetActionsOrganismAAcetylcholinesteraseactivatorHumansACholinesteraseactivatorHumans",[],"['Amines', 'Antidotes', 'Cholinergic Agents', 'Cholinesterase Reactivators', 'Compounds used in a research, industrial, or household setting', 'Drugs that are Mainly Renally Excreted', 'Enzyme Reactivators', 'Hydroxylamines', 'Neurotransmitter Agents', 'Oximes', 'Protective Agents']" +DB00990,Exemestane,Exemestaneis an aromatase inhibitor used to treat breast cancer in postmenopausal women after treatment with tamoxifen.,['P11511'],"Aromatase is an enzyme that converts hormones to estrogen in the body's adrenal glands. The aromatase inhibitors (AIs) are drugs that reduce estrogen levels by blocking the action of aromatase in the adrenal glands. The selective AIs (SAIs) selectively reduce levels of estrogen without interfering with levels of other steroid hormones that are produced by the adrenal gland. Drugs in this class include anastrozole (Arimidex ™), letrozole (Femara ™) and exemestane (Aromasin ™).",[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC(=C)C2=CC(=O)C=C[C@]12C,"Breast cancer cell growth may be estrogen-dependent. Aromatase (exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It irreversibly binds to the active site causing permanent inhibition necessitating de novo synthesis to restore enzymatic function. Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on the adrenal biosynthesis of corticosteroids or aldosterone. This reduction in serum and tumor concentrations of estrogen delays tumor growth and disease progression. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least times higher than that inhibiting the aromatase enzyme.TargetActionsOrganismACytochrome P AinhibitorHumans",[],"['Androstanes', 'Androstenes', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Aromatase Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Enzyme Inhibitors', 'Estrogen Antagonists', 'Fused-Ring Compounds', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Steroid Synthesis Inhibitors', 'Steroids']" +DB04960,Tipifarnib,"Tipifarnib (R-115777) is a substance that is being studied in the treatment of acute myeloid leukemia (AML) and other types of cancer. It belongs to the family of drugs called farnesyltransferase inhibitors. It is also called Zarnestra. In June 2005, the FDA issued a Not Approvable Letter for Zarnestra.",['P49356'],"R115777, a nonpeptidomimetic farnesyl transferase inhibitor, suppresses the growth of human pancreatic adenocarcinoma cell lines. This growth inhibition is associated with modulation in the phosphorylation levels of signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinases (ERK).",CN1C=NC=C1[C@@](N)(C1=CC=C(Cl)C=C1)C1=CC2=C(C=C1)N(C)C(=O)C=C2C1=CC(Cl)=CC=C1,"The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. After translation, RAS goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-RAS protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-RAS. Farnesyl is necessary to attach RAS to the cell membrane. Without attachment to the cell membrane, RAS is not able to transfer signals from membrane receptors (Reuter et al., ).TargetActionsOrganismUProtein farnesyltransferase subunit betaNot AvailableHumans",[],"['Antineoplastic Agents', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'Quinolines']" +DB11641,Vinflunine,Vinflunineis a vinca alkaloid used to treat advanced or metastatic transitional cell carcinoma of the urothelial tract after a platinum containing treatment has failed.,['P07437'],"The antitumour effects of vinflunine are dependent on concentration and exposure duration of the drug1. Vinflunine mediates an anti-mitotic action by inhibiting the microtubule assembly at micromolar concentrations and reducing the rate and extent of microtubule growing events1.In vivo, vinflunine displays a significant antitumor activity against a broad spectrum of human xenografts in mice both in terms of survival prolongation and tumour growth inhibition6. Compared with other vinca alkaloids, vinflunine is a less-potent inductor of drug resistancein vitro3.",CC[C@@]12C=CCN3CC[C@@]4([C@H]13)[C@@H](N(C)C1=CC(OC)=C(C=C41)[C@]1(C[C@@H]3C[C@H](C[N@@](C3)CC3=C1NC1=CC=CC=C31)C(C)(F)F)C(=O)OC)[C@](O)([C@@H]2OC(C)=O)C(=O)OC,"Microtubules are a major component of the cytoskeleton that have a critical role in maintenance of cell shape, mobility, adhesion and intracellular integrity. They also play a role in the formation of the mitotic spindle and chromosomal segregation to the daughter cells at mitosis. Via GTP hydrolysis at the β-tubulin subunit and polymerization of tubulin into linear polymers, microtubules, or macromolecular filaments composed of tubulin heterodimers, are formed via a mechanism of nucleation-elongation. At the onset of mitosis, the interphase microtubule network disassembles into the tubulin. The tubulin reassembles into a new population of mitotic spindle microtubules that further undergo rapid successions of lengthening and shortening until they are attached to the newly duplicated sister chromatids at their centromeres. The dynamic behaviour of microtubules are characterized by two mechanical process: dynamic instability indicating repeated switches of growth and shortening at the ends, and microtubule treadmilling that involves the fast-growing (+) end of the microtubule accompanied by a net loss of the opposite slow-growing (-) end. Microtubule treadmilling plays a critical role in mitosis by generating the forces for separation of the chromosomes in the mitotic spindle from centrosome and kinetochores.In both cancer and normal cells, vinflunine binds to tubulin at or near to the vinca binding sites at β-tubulin. It is proposed that in similarity to other vinca alkaloids, vinflunine is most likely to bind to β-tubulin subunit at the interdimer interface. Via direct binding to tubulin, vinflunine inhibits microtubule polymerization and induces a G+M arrest, or a mitotic arrest. Vinflunine disrupts the dynamic function of microtubules by suppressing treadmilling and slowing the microtubule growth rate while increasing growth duration. Ultimately, mitotic accumulation at the metaphase/anaphase transition results in cell apoptosis.TargetActionsOrganismATubulin beta chaininhibitorHumans",[],"['Alkaloids', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Secologanin Tryptamine Alkaloids', 'Vinca Alkaloids']" +DB01126,Dutasteride,Dutasterideis an antiandrogenic compound that is used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in adult males by inhibiting 5-alpha reductase.,"['P18405', 'P31213']","Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Dutasteride works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with tamsulosin.14The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect observed within 1-2 weeks following initial administration.15After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively.15The serum concentrations of DHT were maintained to be decreased by more than 90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day.5As evident from the clinical studies, dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.15",[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])NC(=O)C=C[C@]4(C)[C@@]3([H])CC[C@]12C)C(=O)NC1=CC(=CC=C1C(F)(F)F)C(F)(F)F,"The α-reductase is a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, α-dihydrotestosterone (DHT).DHT is considered to be the primary androgen playing a role in the initial development and subsequent enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland.DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosteroneand by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation.Responsible for the synthesis of approximately one-third of circulating DHT, type I α-reductase is predominant in the sebaceous glands of most regions of skin, including the scalp, and liver. The type II a-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT.Due to its dual inhibition of both isoenzymes of α-reductase, dutasteride causes a near-complete suppression of DHT.Compared to a % reduction of serum DHT levels caused byfinasteride, a near-complete suppression of serum DHT-more than % is seen with dutasteride.By forming a stable complex with both type II and type II α-reductase, dutasteride inhibits its enzymatic action of converting testosterone to α-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. It is proposed that DHT is the principal androgen responsible for prostatic growth in later life-normal masculinization of the external genitalia and maturation of the prostate gland during development-thus reducing the serum DHT levels results in reduced prostatic volume and increased epithelial apoptosis.Dutasteride is a competitive and specific inhibitor of both Type I and Type II α-reductase isoenzymes and when evaluated underin vitroandin vivoconditions, the dissociation of the drug from the drug-enzyme complex is reported to be extremely slow.Dutasteride does not bind to the human androgen receptor.TargetActionsOrganismA-oxo--alpha-steroid -dehydrogenase inhibitorHumansA-oxo--alpha-steroid -dehydrogenase inhibitorHumans",[],"['5-alpha Reductase Inhibitors', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Azasteroids', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Benign Prostatic Hypertrophy', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Steroid Synthesis Inhibitors', 'Steroids', 'Urologicals']" +DB13953,Estradiol benzoate,Estradiol benzoateis an estrogen indicated in combination with progesterone for the treatment of irregular menstruation.,"['P03372', 'Q92731', 'O75469', 'P43681', 'Q15596', 'Q99527', 'P00846', 'Q14457', 'P37059', 'P62508']","Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level.",[H][C@]1(O)CC[C@@]2([H])[C@]3([H])CCC4=CC(OC(=O)C5=CC=CC=C5)=CC=C4[C@@]3([H])CC[C@]12C,"Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.TargetActionsOrganismAEstrogen receptor alphaagonistHumansAEstrogen receptor betaagonistHumansUNuclear receptor subfamily group I member Not AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNuclear receptor coactivator Not AvailableHumansUG-protein coupled estrogen receptor Not AvailableHumansUATP synthase subunit aNot AvailableHumansUBeclin-Not AvailableHumansUEstradiol -beta-dehydrogenase Not AvailableHumansUEstrogen-related receptor gammaligandHumans",[],"['Adrenal Cortex Hormones', 'BCRP/ABCG2 Inhibitors', 'Contraceptive Agents, Hormonal', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Estrogens', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein substrates', 'Reproductive Control Agents', 'Steroids', 'UGT1A1 Substrates']" +DB00336,Nitrofural,Nitrofuralis a topical antibacterial for the prevention and treatment of bacterial infections of the skin.,['P06715'],"Nitrofurazone is a topical antibacterial agent indicated as an adjunctive therapy for second and third degree burns when resistance to other agents is a real or potential problem. Nitrofurazone is also indicated in skin grafting when bacterial contamination may cause graft rejection or donor site infection, especially in hospitals with a history of resistant bacteria.",NC(=O)N\N=C\C1=CC=C(O1)[N+]([O-])=O,"The exact mechanism of action is unknown. Nitrofurazone inhibits several bacterial enzymes, especially those involved in the aerobic and anaerobic degradation of glucose and pyruvate. This activity is believed also to affect pyruvate dehydrogenase, citrate synthetase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase.TargetActionsOrganismAGlutathione reductaseinhibitorEscherichia coli (strain K)",[],"['Agents Against Leishmaniasis and Trypanosomiasis', 'Anti-Infective Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Antiseptics and Disinfectants', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Dermatologicals', 'Furans', 'Irrigating Solutions', 'Medicated Dressings', 'Medicated Dressings With Antiinfectives', 'Nitro Compounds', 'Nitrofuran Derivatives', 'Nitrofurans', 'Ophthalmologicals', 'Otologicals', 'Sensory Organs']" +DB11431,Moxidectin,"Moxidectin is a potent, broad-spectrum endectocide (antiparasitic that is active against endo- and ecto-parasites) with activity against nematodes, insects, and acari. It was first used in cattle followed by an approved use in general animals. It is a semi-synthetic methoxine derivative of nemadectin which is a 16-member pentacyclic lactone of the milbemycin class. Moxidectin differs by the absence of a disaccharide moiety on carbon 13, a substituted olefinic side chain at carbon 25 and a unique methoxime moiety at carbon 23. Due to these modifications, moxidectin is classified as a second generation macrocyclic lactone.1Moxidectin was developed by Medicines Development for Global Health and FDA approved in June 13, 2018.7",['Q25634'],"Moxidectin has been reported to be highly effective againstOnchocerca volvuluswhen compared to ivermectin.3When moxidectin was administered in infected individuals, the microfilarial load in the skin was lower even when compared to the current therapy, ivermectin. The levels of microfilarial got reduced to an undetectable level while being safe to be used in mass drug administration.9",[H][C@@]12OC\C3=C/C=C/[C@H](C)C\C(C)=C\C[C@]4([H])C[C@@]([H])(C[C@]5(C\C(=N/OC)[C@H](C)[C@H](O5)C(\C)=C\C(C)C)O4)OC(=O)[C@]([H])(C=C(C)[C@H]1O)[C@@]23O,"Moxidectin selectively binds to the parasite's GABA-A and glutamate-gated chloride ion channels which are vital for the function of invertebrate nerve and muscle cells. It presents activity against the parasite but it does not kill him.Once moxidectin is bound, there is an increased permeability leading to an influx of chloride ions and flaccid paralysis of the parasite.TargetActionsOrganismAGlutamate-gated chloride channelbinderOnchocerca volvulusAGABA-A gated chloride channelbinderOnchocerca volvulusNABC transportersbinderOnchocerca volvulus",[],"['Agrochemicals', 'Anthelmintics', 'Anti-Infective Agents', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Compounds used in a research, industrial, or household setting', 'Insecticides', 'Lactones', 'Pesticides', 'Polyketides', 'Toxic Actions']" +DB00539,Toremifene,Toremifeneis a first generation nonsteroidal selective estrogen receptor modulator used to treat certain breast cancers.,"['P03372', 'P04278']","Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein.",CN(C)CCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1,"Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors.TargetActionsOrganismAEstrogen receptor alphamodulatorHumansUSex hormone-binding globulinNot AvailableHumans",[],"['Anti-Estrogens', 'Antineoplastic Agents', 'Antineoplastic Agents, Hormonal', 'Antineoplastic and Immunomodulating Agents', 'Benzene Derivatives', 'Benzylidene Compounds', 'Bone Density Conservation Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Endocrine Therapy', 'Estrogen Agonist/Antagonist', 'Estrogen Receptor Modulators', 'Highest Risk QTc-Prolonging Agents', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'QTc Prolonging Agents', 'Selective Estrogen Receptor Modulators', 'Stilbenes']" +DB02342,2-Methoxyestradiol,2-Methoxyestradiol (2ME2) is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It has undergone Phase 1 clinical trials against breast cancers and preclinical studies suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis.,"['P21964', 'P04798', 'Q16678', 'P11511', 'Q16665']",2-Methoxyestradiol belongs to the family of drugs called angiogenesis inhibitors. It also acts as a vasodilator.,[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C(OC)=C3,"-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. -methoxyestradiol is a naturally occurring estrogen metabolite but has no undesired estrogenic activity.TargetActionsOrganismUCatechol O-methyltransferaseNot AvailableHumansUCytochrome P ANot AvailableHumansUCytochrome P BNot AvailableHumansUCytochrome P ANot AvailableHumansUHypoxia-inducible factor -alphaNot AvailableHumans",[],"['Antimitotic Agents', 'Antineoplastic Agents', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Mitosis Modulators', 'Steroids', 'Tubulin Modulators']" +DB01259,Lapatinib,Lapatinibis an antineoplastic agent and tyrosine kinase inhibitor used for the treatment of advanced or metastatic HER-positive breast cancer in patients who received prior chemotherapeutic treatments.,"['P00533', 'P04626']","Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. An anti-cancer drug, lapatinib was developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine.",CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1,Lapatinib is a -anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both epidermal growth factor receptor (HER/EGFR/ERBB) and human epidermal growth factor receptor type (HER/ERBB)with a dissociation half-life of ≥ minutes. Lapatinib inhibits ERBB-driven tumor cell growth in vitro and in various animal models. An additive effect was demonstrated in an in vitro study when lapatinib and -florouracil (the active metabolite of capecitabine) were used in combination in the tumor cell lines tested. The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines. Lapatinib retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro. These in vitro findings suggest non-cross-resistance between these two agents.TargetActionsOrganismAEpidermal growth factor receptorantagonistHumansAReceptor tyrosine-protein kinase erbB-antagonistHumans,[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Hepatotoxic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors', 'Kinase Inhibitor', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Quinazolines', 'Tyrosine Kinase Inhibitors']" +DB00140,Riboflavin,Riboflavinis a vitamin used to correct vitamin B2 deficiency.,"['Q969G6', 'P0AFU8', 'P30043']","Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts.",CC1=C(C)C=C2N(C[C@H](O)[C@H](O)[C@H](O)CO)C3=NC(=O)NC(=O)C3=NC2=C1,"Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase.TargetActionsOrganismARiboflavin kinaseligandHumansARiboflavin synthaseotherEscherichia coli (strain K)AFlavin reductase (NADPH)product ofHumans","['Dietary and Nutritional Therapies', 'Nutritional supplementation', 'Vitamin supplementation', 'Dietary supplementation']","['Alimentary Tract and Metabolism', 'Biological Factors', 'Coenzymes', 'Dermatologicals', 'Enzymes and Coenzymes', 'Flavins', 'Heterocyclic Compounds, Fused-Ring', 'Micronutrients', 'OAT1/SLC22A6 inhibitors', 'Ophthalmologicals', 'Photosensitizing Agents', 'Pigments, Biological', 'Pteridines', 'Radiation-Sensitizing Agents', 'Sensory Organs', 'Vitamin B Complex', 'Vitamins']" +DB09074,Olaparib,"Olaparibis a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer.","['P09874', 'Q9UGN5', 'Q9Y6F1', 'P42330']","Olaparib is a cytotoxic and anti-tumour agent. Olaparib inhibits the growth of selective tumour cell linesin vitroand decreases tumour growth in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy. The drug exerts anti-tumour effects in cell lines and mouse tumour models with deficiencies in BRCA1/2, ATM, or other genes involved in the homologous recombination repair (HRR) of DNA damage and correlated with platinum response.8In preclinical models of cancer, olaparib demonstrated anti-tumour activity when used alone, in combination with chemotherapeutic agents, or radiotherapy.5Olaparib can act as a chemosensitizer to potentiate the cytotoxicity of DNA-damaging chemotherapeutic agents such as alkylating agents and platinum-based drugs. It can also act as a radiosensitizer by preventing PARP-mediated DNA repair.2,4",FC1=CC=C(CC2=NNC(=O)C3=CC=CC=C23)C=C1C(=O)N1CCN(CC1)C(=O)C1CC1,"Poly(ADP-ribose) polymerases (PARPs) are multifunctional enzymes comprising members. They are involved in essential cellular functions, such as DNA transcription and DNA repair.PARPs recognize and repair cellular DNA damage, such as single-strand breaks (SSBs) and double-strand breaks (DSBs). Different DNA repair pathways exist to repair these DNA damages, including the base excision repair (BER) pathway for SSBs and BRCA-dependent homologous recombination for DSBs.Olaparib is a PARP inhibitor: while it acts on PARP, PARP, and PARP, olaparib is a more selective competitive inhibitor of NAD+at the catalytic site of PARP and PARP. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of DSBs, which is the most toxic form of DNA damage. While BRCA-dependent homologous recombination can repair DSBs in normal cells, this repair pathway is defective in cells with BRCA/ mutations, such as certain tumour cells.Inhibition of PARP in cancer cells with BRCA mutations leads to genomic instability and apoptotic cell death. This end result is also referred to as synthetic lethality, a phenomenon where the combination of two defects - inhibition of PARP activity and loss of DSB repair by HR - that are otherwise benign when alone, lead to detrimental results.In vitrostudies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.TargetActionsOrganismAPoly [ADP-ribose] polymerase inhibitorHumansAPoly [ADP-ribose] polymerase inhibitorHumansAPoly [ADP-ribose] polymerase inhibitorHumansUAldo-keto reductase family member CinhibitorHumans",['Maintenance therapy'],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'MATE 1 Inhibitors', 'MATE 2-K Inhibitors', 'MATE inhibitors', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Poly (ADP-ribose) polymerase (PARP) inhibitors', 'Poly(ADP-ribose) Polymerase Inhibitors', 'Pyridazines', 'UGT1A1 Inhibitors']" +DB04574,Estrone sulfate,Estrone sulfateis an estrogen used as monotherapy or in several combination hormone replacement products for managing menopause symptoms and hormone disorders.,"['P03372', 'Q92731']","Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.",[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(OS(O)(=O)=O)C=C3,"Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.TargetActionsOrganismAEstrogen receptor alphaagonistHumansUEstrogen receptor betaagonistHumans",[],"['17-Ketosteroids', 'Adrenal Cortex Hormones', 'Contraceptive Agents, Hormonal', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Estradiol Congeners', 'Estranes', 'Estrenes', 'Estrogens', 'Estrogens, Conjugated (USP)', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormonal Contraceptives for Systemic Use', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Ketosteroids', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'NTCP Inhibitors', 'Reproductive Control Agents', 'Steroids', 'Thyroxine-binding globulin inducers']" +DB01324,Polythiazide,Polythiazideis a thiazide diuretic used in the management of hypertension and treatment of edema.,['P55017'],"As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure",CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O,"As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.TargetActionsOrganismASolute carrier family member inhibitorHumans",[],"['Amides', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzothiadiazines', 'Cardiovascular Agents', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Increased Diuresis', 'Membrane Transport Modulators', 'Natriuretic Agents', 'OAT3/SLC22A8 Substrates', 'Photosensitizing Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB08816,Ticagrelor,"Ticagreloris a P2Y12 platelet inhibitor used in patients with a history of myocardial infarction or with acute coronary syndrome (ACS) to prevent future myocardial infarction, stroke and cardiovascular death.",['Q9H244'],"Ticagrelor is a P2Y12receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke.1,3It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated.6,7Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.6",CCCSC1=NC2=C(N=NN2[C@@H]2C[C@H](OCCO)[C@@H](O)[C@H]2O)C(N[C@@H]2C[C@H]2C2=CC(F)=C(F)C=C2)=N1,"Ticagrelor is a PYreceptor antagonist.The PYreceptor couples with Gαiand other Giproteins which inhibit adenylyl cyclase.Gimediated signalling also activates PIK, Akt, Rapb, and potassium channels.The downstream effects of these activities mediate hemostasis and lead to platelet aggregation.Antagonism of the PYreceptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke.TargetActionsOrganismAPY purinoceptor inhibitorHumans",[],"['Anticoagulants', 'Antiplatelet agents', 'Blood and Blood Forming Organs', 'Carbohydrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (weak)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Platelet Aggregation', 'Glycosides', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P2Y12 Platelet Inhibitor', 'Phenylalanine Hydroxylase Activators', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Purine Nucleosides', 'Purinergic Agents', 'Purinergic Antagonists', 'Purinergic P2 Receptor Antagonists', 'Purinergic P2Y Receptor Antagonists', 'Purines', 'Ribonucleosides']" +DB01166,Cilostazol,Cilostazolis an antiplatelet agent and vasodilator used for the symptomatic relief of intermittent claudication.,['Q14432'],"Cilostazol reduces the symptoms of intermittent claudication, as indicated by an increased walking distance. Intermittent claudication is pain in the legs that occurs with walking and disappears with rest. The pain occurs due to reduced blood flow to the legs.",O=C1CCC2=C(N1)C=CC(OCCCCC1=NN=NN1C1CCCCC1)=C2,"Cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation.TargetActionsOrganismAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumans",[],"['Agents producing tachycardia', 'Anti-Asthmatic Agents', 'Antiplatelet agents', 'Autonomic Agents', 'Blood and Blood Forming Organs', 'Bronchodilator Agents', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Fibrin Modulating Agents', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Neuroprotective Agents', 'Peripheral Nervous System Agents', 'Phosphodiesterase 3 Inhibitors', 'Phosphodiesterase Inhibitors', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Potential QTc-Prolonging Agents', 'Protective Agents', 'QTc Prolonging Agents', 'Quinolines', 'Respiratory System Agents', 'Tetrazoles', 'Vasodilating Agents']" +DB00467,Enoxacin,A broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid.,"['P43700', 'P43702', 'P11388']","Enoxacin is a quinolone/fluoroquinolone antibiotic. Enoxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Enoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Enoxacin may be active against pathogens resistant to drugs that act by different mechanisms.",CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N=C12)N1CCNCC1,Enoxacin exerts its bactericidal action via the inhibition of the essential bacterial enzyme DNA gyrase (DNA Topoisomerase II).TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)NDNA topoisomerase -alphainhibitorHumans,[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00671,Cefixime,Cefiximeis a third generation cephalosporin used to treat susceptible Gram negative and Gram positive bacterial infections.,['P44469'],"Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.",[H][C@]12SCC(C=C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OCC(O)=O)\C1=CSC(N)=N1)C(O)=O,"Like all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta Lactam Antibiotics', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00618,Demeclocycline,Demeclocyclineis a tetracycline antibiotic used to treat a wide variety of susceptible bacterial infections.,['P30518'],"Demeclocycline is a tetracycline antibiotic active against the following microorganisms:Rickettsiae(Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers),Mycoplasma pneumoniae(PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis),Haemophilus ducreyi(chancroid),Yersinia pestis,Pasteurella pestisandPasteurella tularensis,Bartonella bacilliformis,Bacteroides species,Vibrio commaandVibrio fetus, andBrucella species(in conjunction with streptomycin). Demeclocycline inhibits cell growth by inhibiting translation. Demeclocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Demeclocycline is not a direct bactericidal agent; rather, it is a bacteriostatic drug that impairs bacterial growth. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time.",[H][C@]12C[C@@]3([H])[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]3(O)C(O)=C1C(=O)C1=C([C@H]2O)C(Cl)=CC=C1O,"Demeclocycline inhibits cell growth by inhibiting translation. It binds (reversibly) to the S and S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.TargetActionsOrganismAS ribosomal proteininhibitorUVasopressin V receptorinhibitorHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives for Systemic Use', 'Dermatologicals', 'Drugs causing inadvertant photosensitivity', 'Naphthacenes', 'Photosensitizing Agents', 'Tetracyclines']" +DB01022,Vitamin K1,Vitamin K1is a fat soluble vitamin used to treat hemorrhagic conditions in infants and coumarin overdoses.,"['P38435', 'P02818']","Phylloquinone is a vitamin K indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K.17It has a long duration of action as vitamin K is cycled in the body,6and a wide therapeutic index as large doses can be tolerated.9,18Patients should have their prothrombin time monitored during therapy and healthcare professionals should be aware of the increased risk of hypersensitivity reactions with parenteral administration.18",CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CC1=C(C)C(=O)C2=C(C=CC=C2)C1=O,"Vitamin K is a cofactor of gamma-carboxylase.,Gamma carboxylase attaches carboxylic acid functional groups to glutamate, allowing precursors of factors II, VII, IX, and X to bind calcium ions.Binding of calcium ions converts these clotting factors to their active form, which are then secreted from hepatocytes into the blood, restoring normal clotting function.Vitamin K may also carboxylate matrix proteins in chondrocytes, inhibiting calcification of joints, and may increase type II collagen.The role of vitamin K in osteroarthritis,bone density,and vascular calcificationis currently under investigation.TargetActionsOrganismAVitamin K-dependent gamma-carboxylasesubstrateinducercofactorHumansUOsteocalcinagonistHumans",['Vitamin supplementation'],"['Blood and Blood Forming Organs', 'Coagulants', 'Diet, Food, and Nutrition', 'Diterpenes', 'Drugs that are Mainly Renally Excreted', 'Fibrin Modulating Agents', 'Food', 'Growth Substances', 'Hematologic Agents', 'Hemostatics', 'Increased Prothrombin Activity', 'Micronutrients', 'Naphthalenes', 'Naphthoquinones', 'Physiological Phenomena', 'Phytol', 'Quinones', 'Reversed Anticoagulation Activity', 'Terpenes', 'Vitamin K', 'Vitamins', 'Vitamins (Fat Soluble)', 'Warfarin Reversal Agent']" +DB00760,Meropenem,Meropenemis a carbapenem antibiotic used to treat a wide variety of infections in the body.,['P24228'],"Meropenem is a broad-spectrum carbapenem antibiotic. It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death.",[H][C@]1([C@@H](C)O)C(=O)N2C(C(O)=O)=C(S[C@@H]3CN[C@@H](C3)C(=O)N(C)C)[C@H](C)[C@]12[H],"The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding- protein (PBP) targets. Its strongest affinities are toward PBPs , and ofEscherichia coliandPseudomonas aeruginosa; and PBPs , and ofStaphylococcus aureus.TargetActionsOrganismAD-alanyl-D-alanine carboxypeptidase DacBinhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Carbapenems', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penem Antibacterial', 'Sulfur Compounds', 'Thienamycins']" +DB01141,Micafungin,"Micafunginis an antifungal agent used for the treatment of candidemia, acute disseminated candidiasis, and certain other invasive Candida infections, and for the prophylaxis of Candida infections during stem cell transplantation.",['A2QLK4'],"Formerly known as FK463, micafungin is a semisynthetic lipopeptide synthesized from a fermentation product ofColeophoma empetrithat works as an antifungal agent. It is a glucan synthesis inhibitor of the echinocandin structural class. The U.S. Food and Drug Administration approved micafungin in March 2005. Micafungin inhibits an enzyme essential for fungal cell-wall synthesis. Depending on its concentration, micafungin may be fungicidal against someCandida, but is usually fungistatic againstApergillus. Micafungin can be used concomitantly with a variety of other drugs, including the HIV protease inhibitor ritonavir and the transplant medications cyclosporine and tacrolimus.",CCCCCOC1=CC=C(C=C1)C1=CC(=NO1)C1=CC=C(C=C1)C(=O)N[C@H]1C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)[C@@H](C)CN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC1=O)[C@@H](C)O)[C@H](O)[C@@H](O)C1=CC(OS(O)(=O)=O)=C(O)C=C1)[C@H](O)CC(N)=O,"Micafungin inhibits the synthesis of beta-,-D-glucan, an essential component of fungal cell walls which is not present in mammalian cells. It does this by inhibiting beta-,-D-glucan synthase.TargetActionsOrganismA,-beta-glucan synthase component FKSinhibitorAspergillus niger (strain CBS . / FGSC A)",[],"['Amino Acids, Peptides, and Proteins', 'Anti-Infective Agents', 'Antifungal Agents', 'Antiinfectives for Systemic Use', 'Antimycotics for Systemic Use', 'COMT Substrates', 'Echinocandin Antifungal', 'Echinocandins', 'Lipids', 'Lipopeptides', 'Peptides', 'Peptides, Cyclic']" +DB01208,Sparfloxacin,Sparfloxacinis a fluoroquinolone antibiotic used to treat bacterial respiratory infections and sinusitis.,"['P43700', 'P43702', 'P11388']","Sparfloxacin is a synthetic fluoroquinolone broad-spectrum antimicrobial agent in the same class as ofloxacin and norfloxacin. Sparfloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription. Quinolones differ in chemical structure and mode of action from (beta)-lactam antibiotics. Quinolones may, therefore, be active against bacteria resistant to (beta)-lactam antibiotics. Although cross-resistance has been observed between sparfloxacin and other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to sparfloxacin. In vitro tests show that the combination of sparfloxacin and rifampin is antagonistic against Staphylococcus aureus.",C[C@H]1CN(C[C@@H](C)N1)C1=C(F)C(N)=C2C(=O)C(=CN(C3CC3)C2=C1F)C(O)=O,"The bactericidal action of sparfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase -alphainhibitorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs for Treatment of Tuberculosis', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'P-glycoprotein substrates', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB06777,Chenodeoxycholic acid,Chenodeoxycholic acidis a bile acid used for the treatment of primary biliary cirrhosis.,"['Q96RI1', 'O75469', 'Q8TDU6', 'P52895']","It acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic acid is ineffective with stones of a high calcium or bile acid content.",[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O,"Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids.TargetActionsOrganismUBile acid receptorotherHumansUNuclear receptor subfamily group I member Not AvailableHumansUG-protein coupled bile acid receptor Not AvailableHumansUAldo-keto reductase family member CsubstrateHumans",[],"['Alimentary Tract and Metabolism', 'Bile Acid Preparations', 'Bile acids and derivatives', 'Bile Acids and Salts', 'Bile and Liver Therapy', 'Bile Therapy', 'Cholanes', 'Cholic Acids', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Gastrointestinal Agents', 'Steroids', 'UGT2B7 Inhibitors']" +DB08916,Afatinib,Afatinibis an antineoplastic agent used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with non-resistant EGFR mutations or resistance to platinum-based chemotherapy.,"['P00533', 'P04626', 'Q15303']","Aberrant ErbB signaling triggered by receptor mutations, and/or amplification, and/or receptor ligand overexpression contributes to the malignant phenotype3. Mutation in EGFR defines a distinct molecular subtype of lung cancer3.In non-clinical disease models with ErbB pathway deregulation, afatinib as a single agent effectively blocks ErbB receptor signaling resulting in tumor growth inhibition or tumor regression3. NSCLC tumors with common activating EGFR mutations (Del 19, L858R) and several less common EGFR mutations in exon 18 (G719X) and exon 21 (L861Q) are particularly sensitive to afatinib treatment in non-clinical and clinical settings3. Limited non-clinical and/or clinical activity was observed in NSCLC tumors with insertion mutations in exon 203.The acquisition of a secondary T790M mutation is a major mechanism of acquired resistance to afatinib and gene dosage of the T790M-containing allele correlates with the degree of resistance in vitro3. The T790M mutation is found in approximately 50% of patients' tumors upon disease progression on afatinib, for which T790M targeted EGFR TKIs may be considered as a next line treatment option3. Other potential mechanisms of resistance to afatinib have been suggested preclinically and MET gene amplification has been observed clinically3.At the same time, the effect of multiple doses of afatinib (50 mg once daily) on cardiac electrophysiology and the QTc interval was evaluated in an open-label, single-arm study in patients with relapsed or refractory solid tumorsLabel. Ultimately, no large changes in the mean QTc interval (i.e., >20 ms) were detected in the studyLabel.",CN(C)C\C=C\C(=O)NC1=C(O[C@H]2CCOC2)C=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1,"Afatinib is a potent and selective, irreversible ErbB family blocker. Afatinib covalently binds to and irreversibly blocks signaling from all homo and heterodimers formed by the ErbB family members EGFR (ErbB), HER (ErbB), ErbB and ErbB.In particular, afatinib covalently binds to the kinase domains of EGFR (ErbB), HER (ErbB), and HER (ErbB) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signalingLabel. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLCLabel. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by ) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or ) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methodsLabel. The most commonly found of these mutations are exon LR substitutions and exon deletionsLabel.Moreover, afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon deletion mutations, exon LR mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patientsLabel. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HERLabel.TargetActionsOrganismAEpidermal growth factor receptorinhibitorHumansAReceptor tyrosine-protein kinase erbB-inhibitorHumansAReceptor tyrosine-protein kinase erbB-inhibitorHumans",[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Enzyme Inhibitors', 'Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Kinase Inhibitor', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protein Kinase Inhibitors', 'Quinazolines', 'Tyrosine Kinase Inhibitors']" +DB09330,Osimertinib,Osimertinibis a tyrosine kinase inhibitor used in the treatment of certain types of non-small cell lung carcinoma.,['P00533'],A pharmacokinetic/pharmacodynamic analysis suggested a concentration-dependent QTc interval prolongation of 14 msec (upper bound of two-sided 90% CI: 16 msec) at a dose of osimertinib 80 mg.9,COC1=C(NC2=NC=CC(=N2)C2=CN(C)C3=C2C=CC=C3)C=C(NC(=O)C=C)C(=C1)N(C)CCN(C)C,"Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that binds to certain mutant forms of EGFR (TM, LR, and exon deletion) that predominate in non-small cell lung cancer (NSCLC) tumours following treatment with first-line EGFR-TKIs.As a third-generation tyrosine kinase inhibitor, osimertinib is specific for the gate-keeper TM mutation which increases ATP binding activity to EGFR and results in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.,Compared to wild-type EGFR, osimertinib has times higher affinity for EGFR molecules with the LR/TM mutationin vitro.,TargetActionsOrganismAEpidermal growth factor receptorinhibitorregulatorHumans",['First Line Chemotherapy'],"['Acids, Acyclic', 'Acrylates', 'Amides', 'Amines', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Protein Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB11737,Icotinib,"Icotinib is a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) +Icotinib was approved in China by the SFDA in June, 2011 and in January 2014, Beta Pharma, Inc. was given a “May Proceed” from the US FDA to conduct a Phase I study for the evaluation of icotinib as a treatment of EGFR+ Non-Small Cell Lung Cancer (NSCLC).",['P00533'],"In vitro: Icotinib inhibits EGFR activity in a dose-dependent manner, with an IC50 value of 5 nM and complete inhibition at 62.5 nM. Icotinib selectively solely inhibits the EGFR members including the wild type and mutants with inhibition efficacies of 61-99%. Icotinib blocks EGFR-mediated intracellular tyrosine phosphorylation in human epidermoid carcinoma A431 cells in a dose-dependent manner. Meanwhile, in the proliferation assay performed on A431, BGC-823, A549, H460, HCT8, KB and Bel-7402 cell lines, it was found that the relative sensitivity of cell lines to Icotinib is A431 > BGC-823 > A549 > H460 > KB > HCT8 and Bel-7402. Icotinib exhibits a broad spectrum of antitumor activity and it is especially effective against tumors expressing higher levels of EGFR. +In vivo: In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120 mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: NCT01040780).",C#CC1=CC=CC(NC2=NC=NC3=CC4=C(OCCOCCOCCO4)C=C23)=C1,"Icotinib is a highly selective, first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) which binds reversibly to the ATP binding site of the EGFR protein, preventing completion of the signal transduction cascade. EGFR is an oncogenic receptor and patients with activating somatic mutations, such as an exon deletion or exon LR mutation, within the tyrosine kinase domain display unchecked cell proliferation.TargetActionsOrganismUEpidermal growth factor receptorantagonistHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Crown Compounds', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (moderate)', 'Cytochrome P-450 CYP3A5 Inducers (weak)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors', 'Ethers', 'Ethers, Cyclic', 'Heterocyclic Compounds, Fused-Ring', 'Protein Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB06626,Axitinib,Axitinibis an oral VEGFR and kinase inhibitor used for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy.,"['P17948', 'P35968', 'P35916']",Axitinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumor growth.,CNC(=O)C1=C(SC2=CC=C3C(NN=C3\C=C\C3=CC=CC=N3)=C2)C=CC=C1,"Axitinib selectively blocks the tyrosine kinase receptors VEGFR- (vascular endothelial growth factor receptor), VEGFR-, and VEGFR-.TargetActionsOrganismAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumans",['First Line Chemotherapy'],"['Acids, Carbocyclic', 'Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Indazoles', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Protein Kinase Inhibitors', 'Pyrazoles', 'Receptor Tyrosine Kinase Inhibitors', 'Tyrosine Kinase Inhibitors', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index', 'Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors']" +DB06589,Pazopanib,Pazopanibis an antineoplastic agent used in the treatment of advanced renal cell cancer and advanced soft tissue sarcoma in patients with prior chemotherapy.,"['P17948', 'P35968', 'P35916', 'P16234', 'P09619', 'P10721', 'P22607', 'Q08881', 'P05230', 'Q9UQQ2']","Pazopanib is a synthetic indazolylpyrimidine and reaches steady state concentrations of >15 μg/ml. This concentration is high enough to observe maximal inhibition of VEGFR2 phosphorylation and some anti-tumour activity (concentration required to inhibit receptors is 0.01 - 0.084 μmol/L). A reduction in tumour blood flow, increased tumour apoptosis, inhibition of tumour growth, reduction in tumour interstitial fluid pressure, and hypoxia in cancer cells can be observed in patients receiving treatment.",CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1,"Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptor-, -, and -, platelet-derived growth factor receptor-alpha, platelet-derived growth factor receptor-beta, and c-kit. These receptor targets are part of the angiogenesis pathway that facilitates the formation of tumour blood vessel for tumour survival and growth.TargetActionsOrganismAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor Not AvailableHumansAPlatelet-derived growth factor receptor alphainhibitorHumansAPlatelet-derived growth factor receptor betainhibitorHumansAMast/stem cell growth factor receptor KitinhibitorHumansUFibroblast growth factor receptor inhibitorHumansUTyrosine-protein kinase ITK/TSKinhibitorHumansUFibroblast growth factor inhibitorHumansUSHB adapter protein inhibitorHumans",[],"['Amides', 'Angiogenesis Inhibitors', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hepatotoxic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Kinase Inhibitor', 'Moderate Risk QTc-Prolonging Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Protein Kinase Inhibitors', 'Pyrazoles', 'QTc Prolonging Agents', 'Receptors, Vascular Endothelial Growth Factor, antagonists & inhibitors', 'Sulfones', 'Sulfur Compounds', 'Tyrosine Kinase Inhibitors', 'UGT1A1 Inhibitors']" +DB01179,Podofilox,Podofiloxis a topical agent used for the treatment of external genital warts and perianal warts.,"['P68366', 'P07437', 'P11388']","Podofilox, also called podophyllotoxin, is a purer and more stable form of podophyllin in which only the biologically active portion of the compound is present. Podofilox is used to remove certain types of warts on the outside skin of the genital areas.",[H][C@]12COC(=O)[C@]1([H])[C@H](C1=CC(OC)=C(OC)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@@H]2O,"The exact mechanism of action is not well understood. It does appear, however, that it and its derivatives may bind and inhibit topoisomerase II during the late S and early G stage. The drug may bind and stabilize the temporary break caused by the enzyme. This disrupts the reparation of the break through which the double-stranded DNA passes, and consequently stops DNA unwinding and replicationTargetActionsOrganismATubulin alpha-A chaininhibitorHumansATubulin beta chaininhibitorHumansADNA topoisomerase -alphainhibitorHumans",[],"['Antimitotic Agents', 'Antineoplastic Agents, Phytogenic', 'Antiviral Agents', 'Benzene Derivatives', 'Benzyl Compounds', 'Decreased Mitosis', 'Dermatologicals', 'Keratolytic Agents', 'Lignans', 'Misc. Skin and Mucous Membrane Agents', 'Mitosis Modulators', 'Naphthalenes', 'Tetrahydronaphthalenes', 'Tubulin Modulators']" +DB00796,Candesartan cilexetil,"Candesartan cilexetilis an angiotensin receptor blocker used to treat hypertension, systolic hypertension, left ventricular hypertrophy, and delay progression of diabetic nephropathy.",['P30556'],"Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS. RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.",CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NN=NN1)C(=CC=C2)C(=O)OC(C)OC(=O)OC1CCCCC1,"Candesartan selectively blocks the binding of angiotensin II to AT in many tissues including vascular smooth muscle and the adrenal glands. This inhibits the AT-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in an overall decrease in blood pressure. Candesartan is greater than , times more selective for AT than AT. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion.TargetActionsOrganismAType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing hyperkalemia', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II Antagonists and Diuretics', 'Angiotensin II receptor antagonists', 'Angiotensin Receptor Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzene Derivatives', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'P-glycoprotein inhibitors', 'UGT1A3 substrates']" +DB09072,Sodium oxybate,Sodium oxybateis a central nervous system depressant used to treat cataplexy and excessive daytime sleepiness (EDS) associated with narcolepsy.,"['Q9UBS5', 'O75899', 'Q9HAB3']","Sodium oxybate works to improve nocturnal sleep, improve alertness the following day, and ameliorate cataplexy. Decreased excessive daytime sleepiness in narcolepsy is observed in higher doses3and at a delayed time.6It is proposed that sodium oxybate increases the time spent in Stages N2 and N3 of sleep and decreases the shift to stages N1/Wake/REM,4resulting in improved continuity of sleep5and deeper sleep.4Sodium oxybate is a central nervous system (CNS) depressant that can cause significant respiratory depression. Due to its physiological and psychological effects, sodium oxybate is associated with a risk for substance misuse and abuse,9addiction, withdrawal syndrome, and overdoses.1Sodium oxybate is a sodium salt of GHB, a naturally occurring CNS depressant that increases dopamine levels and increases serotonin turnover.1Sodium oxybate stimulates growth hormone release, often leading to its misuse as a dietary supplement for bodybuilding.1In patients with narcolepsy, sodium oxybate increases nocturnal growth hormone secretion and slow-wave sleep at night, which is when growth hormone is typically released.3",[Na+].OCCCC([O-])=O,"The physiological actions of sodium oxybate are mediated by gamma-hydroxybutyrate (GHB), its active compound. While the exact mechanism of action of GHB in narcolepsy is not fully understood, it is suggested that GHB has multiple modes of action.At low doses, GHB binds to high- and low-affinity G-protein-coupled GHB receptors. Activation of GHB receptors leads to the release of glutamate, which is an excitatory neurotransmitter. At higher doses, GHB activates GABABreceptors,at noradrenergic and dopaminergic neurons, as well as at thalamocortical neuronsthat are involved in sleep-wake regulation, attention and vigilance.GHB metabolizes to GABA, which modulates GABAAand GABACreceptors.TargetActionsOrganismUGABA(B) ReceptoragonistUGamma-hydroxybutyrate (GHB) receptoragonistHumans",[],"['Acids, Acyclic', 'Adjuvants, Anesthesia', 'Anesthetics', 'Anesthetics, General', 'Anesthetics, Intravenous', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Hydroxy Acids', 'Hydroxybutyrates', 'Miscellaneous Central Nervous System Agents', 'Nervous System']" +DB00284,Acarbose,Acarboseis an alpha-glucosidase inhibitor used in adjunctly with diet and exercise for the management of glycemic control in patients with type 2 diabetes mellitus.,"['O43451', 'P14410', 'P04746', 'P10253']","Acarbose is a complex oligosaccharide that competitively inhibits the ability of brush-border alpha-glucosidase enzymes to break down ingested carbohydrates into absorbable monosaccharides, reducing carbohydrate absorption and subsequent postprandial insulin levels.4Acarbose requires the co-administration of carbohydrates in order to exert its therapeutic effect, and as such should be taken with the first bite of a meal three times daily.7Given its mechanism of action, acarbose in isolation poses little risk of contributing to hypoglycemia - this risk is more pronounced, however, when acarbose is used in conjunction with other antidiabetic therapies (e.g. sulfonylureas, insulin).7Patients maintained on acarbose in addition to other antidiabetic agents should be aware of the symptoms and risks of hypoglycemia and how to treat hypoglycemic episodes. There have been rare post-marketing reports of the development of pneumatosis cystoides intestinalis following treatment with alpha-glucosidase inhibitors - patients experiencing significant diarrhea/constipation, mucus discharge, and/or rectal bleeding should be investigated and, if pneumatosis cystoides intestinalis is suspected, should discontinue therapy.6",[H]C(=O)[C@H](O)[C@@H](O)[C@]([H])(O[C@@]1([H])O[C@H](CO)[C@@]([H])(O[C@H]2O[C@H](C)[C@@H](N[C@@]3([H])C=C(CO)[C@@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)CO,"Alpha-glucosidase enzymes are located in the brush-border of the intestinal mucosa and serve to metabolize oligo-, tri-, and disaccharides (e.g. sucrose) into smaller monosaccharides (e.g. glucose, fructose) which are more readily absorbed.These work in conjunction with pancreatic alpha-amylase, an enzyme found in the intestinal lumen that hydrolyzes complex starches to oligosaccharides.Acarbose is a complex oligosaccharide that competitively and reversibly inhibits both pancreatic alpha-amylase and membrane-bound alpha-glucosidases - of the alpha-glucosidases, inhibitory potency appears to follow a rank order of glucoamylase > sucrase > maltase > isomaltase.By preventing the metabolism and subsequent absorption of dietary carbohydrates, acarbose reduces postprandial blood glucose and insulin levels.TargetActionsOrganismAMaltase-glucoamylase, intestinalinhibitorHumansASucrase-isomaltase, intestinalinhibitorHumansAPancreatic alpha-amylaseinhibitorHumansULysosomal alpha-glucosidaseinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Carbohydrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Glycoside Hydrolase Inhibitors', 'Hypoglycemia-Associated Agents', 'Oligosaccharides', 'Oral Hypoglycemics', 'Polysaccharides', 'Trisaccharides']" +DB04854,Febuxostat,Febuxostatis a xanthine oxidase inhibitor used for the management of chronic hyperuricemia in adults with gout who have an inadequate response or intolerance to allopurinol.,['P47989'],"Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion. Febuxostat at daily doses of 40-80 mg reduced the 24-hour mean serum uric acid concentrations by 40 to 55%.10Closely related to the drug-induced reduction of serum uric acid levels and mobilization of urate crystals in tissue deposits, febuxostat is associated with gout flares.7Unlikeallopurinolandoxypurinol, febuxostat has no inhibitory actions against other enzymes involved in purine and pyrimidine synthesis and metabolism, because it does not structurally resemble purines or pyrimidines.5",CC(C)COC1=C(C=C(C=C1)C1=NC(C)=C(S1)C(O)=O)C#N,"Gout is a form of acute arthritis that is characterized by the accumulation of crystals of monosodium urate and urate crystals in or around a joint, leading to inflammation and persistent urate crystal deposition in bones, joints, tissues, and other organs that may exacerbate over time. Hyperuricemia is closely related to gout, whereby it may exist for many years before the first clinical attack of gout; thus, aberrated serum uric acid levels and hyperuricemia are believed to be the biochemical aberration involved in the pathogenesis of gout.Xanthine oxidoreductase (XOR) can act as a xanthine oxidase or xanthine dehydrogenase. In humans, it is a critical enzyme for uric acid production as it catalyzes the oxidation reaction steps from hypoxanthine to xanthine and from xanthine to uric acid in the pathway of purine metabolism.Febuxostat potently inhibits XOR, blocking both its oxidase and dehydrogenase activities. With high affinity, febuxostat binds to XOR in a molecular channel leading to the molybdenum-pterin active site, whereallopurinoldemonstrates relatively weak competitive inhibition.XOR is mainly found in the dehydrogenase form under normal physiological conditions; however, in inflammatory conditions, XOR can be converted into the xanthine oxidase form, which catalyzes reactions that produce reactive oxygen species (ROS), such as peroxynitrite. ROS contribute to vascular inflammation and alterations in vascular function. As febuxostat can inhibit both forms of XOR, it can inhibit ROS formation, oxidative stress, and inflammation.In a rat model, febuxostat suppressed renal ischemia-reperfusion injury by attenuating oxidative stress.TargetActionsOrganismAXanthine dehydrogenase/oxidaseinhibitorHumans",[],"['Antigout Preparations', 'Antirheumatic Agents', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Musculo-Skeletal System', 'Photosensitizing Agents', 'Preparations Inhibiting Uric Acid Production', 'Sulfur Compounds', 'Thiazoles', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B7 substrates', 'Xanthine Oxidase Inhibitors']" +DB06719,Buserelin,Buserelinis a LHRH agonist used for the palliative treatment of hormone-dependent advanced carcinoma of the prostate gland in males and treatment of endometriosis in females.,"['P22888', 'P30968']","The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects of buserelin on FSH and LH release are 20 to 170 times greater than those of LHRH. Buserelin also has a longer duration of action than natural LHRH. Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours. +Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses (50-500 mcg SC/day or 300-1200 mcg IN/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis.",CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1,"Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of gonadotropin. In males, this results in a reduction in the synthesis and release of testosterone. In females, estrogen secretion is inhibited. While initially, there is a rise in FSH and LH levels, chronic administration of Buserelin results in a sustained suppression of these hormones.TargetActionsOrganismALutropin-choriogonadotropic hormone receptorNot AvailableHumansAGonadotropin-releasing hormone receptorNot AvailableHumans",[],"['Adrenal Cortex Hormones', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Endocrine Therapy', 'Fertility Agents', 'Fertility Agents, Female', 'Gonadotropin-releasing hormone agonist', 'Hormones', 'Hormones and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Hypothalamic Hormones', 'Miscellaneous Therapeutic Agents', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary Hormone-Releasing Hormones', 'Potential QTc-Prolonging Agents', 'Proteins', 'QTc Prolonging Agents', 'Reproductive Control Agents']" +DB06536,Tesaglitazar,"Tesaglitazar is a dual peroxisome proliferator-activated receptor alpha/gamma agonist which improves apolipoprotein levels in non-diabetic subjects with insulin resistance. Tesaglitazar is a proposed treatment for type 2 diabetes and has completed several phase III clinical trials, however in May 2006 AstraZeneca announced that they had discontinued further development.","['Q07869', 'P37231']","Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance.",CCO[C@@H](CC1=CC=C(OCCC2=CC=C(OS(C)(=O)=O)C=C2)C=C1)C(O)=O,TargetActionsOrganismUPeroxisome proliferator-activated receptor alphaNot AvailableHumansUPeroxisome proliferator-activated receptor gammaNot AvailableHumans,[],"['Acids, Carbocyclic', 'Alkanes', 'Alkanesulfonic Acids', 'Hydrocarbons, Acyclic', 'Sulfonic Acids', 'Sulfur Acids', 'Sulfur Compounds']" +DB01048,Abacavir,Abacaviris an antiviral nucleoside reverse transcriptase inhibitor used in combination with other antiretrovirals for the treatment of HIV.,['Q72547'],"Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The concentration of drug necessary to effect viral replication by 50 percent (EC50) ranged from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) and 0.07 to 1.0 μM against HIV-1IIIB and HIV-1BaL, respectively, and was 0.26 ± 0.18 μM against 8 clinical isolates. Abacavir had synergistic activity in cell culture in combination with the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, and the protease inhibitor (PI) amprenavir; and additive activity in combination with the NRTIs didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine.",NC1=NC2=C(N=CN2[C@@H]2C[C@H](CO)C=C2)C(NC2CC2)=N1,"Abacavir is a carbocyclic synthetic nucleoside analogue and an antiviral agent. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analogue of deoxyguanosine-'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV- reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Viral DNA growth is terminated because the incorporated nucleotide lacks a '-OH group, which is needed to form the ′ to ′ phosphodiester linkage essential for DNA chain elongation.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus UHLA class I histocompatibility antigen, B- alpha chainNot AvailableHumans",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'Cycloparaffins', 'Deoxyadenosines', 'Deoxyribonucleosides', 'Dideoxynucleosides', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'Purine Nucleosides', 'Purines', 'Reverse Transcriptase Inhibitors', 'UGT1A1 Substrates']" +DB08818,Hyaluronic acid,"Hyaluronic acidis a glycosaminoglycan used for the relief of joint pain, wound healing, ophthalmologic treatment, cosmetic treatment, and various other applications.","['P16070', 'P05362', 'O75330', 'O14594', 'P13611', 'Q07021', 'P10915', 'Q96S86', 'Q14520', 'Q6UX15', 'Q8WWQ8', 'P98066', 'Q9BZV3', 'Q5JVS0', 'Q9Y5Y7']","HA has long-acting lubricant, shock absorbing, joint stabilizing, and water balancing properties.2,17It is similar to the naturally occurring glycosaminoglycan (GAG) in joints. Hyaluronic acid works by acting as a lubricant and shock absorber, facilitating joint mobility and thereby reducing osteoarthritic pain. Hyaluronic acid has antioxidative, anti-inflammatory, and analgesic effects.2The water-balancing properties and viscoelasticity of hyaluronic acid are beneficial in cosmetic injections, imparting volume and reducing the appearance of imperfections and wrinkles.17Due to the abovementioned properties, HA has a protective effect on the eyes and cornea.3",CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@@H]1O[C@@H]([C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)C(O[C@@H]3O[C@@H]([C@@H](O)[C@H](O)[C@H]3O)C(O)=O)[C@H]2NC(C)=O)[C@H](O)[C@H]1O)C(O)=O,"General principles and hyaluronic acid receptor bindingHyaluronic acid works by two basic mechanisms: serving as a passive structural molecule or serving as signaling molecule, depending on the molecule size. The physicochemical properties of high molecular weight HA contribute to passive structural effects, demonstrating hygroscopicity and viscoelasticity and improving hydration, water balance, and structural integrity. As a signalling molecule interacting with proteins, HA causes several opposing effects based on molecular weight: pro- or anti-inflammatory effects, promotion or inhibition of cell migration, and activating or inhibiting cell division.Hyaluronic acid exerts its therapeutic effects through binding to three primary types of cell surface receptors: CD (a membrane glycoprotein), the receptor for hyaluronate-mediated motility (RHAMM), and the Intercellular Adhesion Molecule (ICAM-). CD is considered the most widely distributed receptor for hyaluronic acid, demonstrating cellular interactions with osteopontin, collagen, and matrix metalloproteinases (MMPs). High and low molecular weight hyaluronic acids demonstrate differing molecular and cellular mechanisms in their interaction with CD receptors. Some examples of these effects include modification of chondrocyte survival pathways in addition to alteration of apoptosis pathways. Lymphatic vessel endothelial hyaluronan receptor (LYVE-), and hyaluronic acid receptor for endocytosis (HARE), (also known as Stabilin-) also bind to hyaluronic acid.Hyaluronic acid for skin conditions and cosmeticsHyaluronic acid's anionic proprieties cause it to attract water and induce swelling, increasing tissue volume and skin structural integrity. The aging process is associated with reduced production of skin hyaluronic acid and collagen, causing the appearance of wrinkles and the loss of facial volume. Dermal fillers of hyaluronic acid replace lost tissue volume, imparting a full and youthful appearance to skin that has lost its elasticity. Hyaluronic acid fillers contain cross-linked hyaluronic acid particles, rendering a concentrated substance with resistance to various forms of physical and chemical breakdown. The cosmetic benefits of hyaluronic acid filler may last up to months, depending on the brand and technique used for injection.Additionally, dermal hyaluronic acid fillers are known to increase the production of fibroblasts, supporting wound healing and offering relief from irritating and inflammatory skin conditions.Hyaluronic acid for joint painMost cells in the human body are capable of synthesizing HA. It is a primary component of the extracellular matrix (ECM) and can be found in bone marrow, cartilage, and synovial fluid in joints.In osteoarthritis, the concentration of naturally occurring hyaluronic acid gradually decreases, lowering the viscosity of synovial fluid that protects joints from excess friction. Administration of intra-articular hyaluronic acid increases viscosity of synovial joint fluid, reducing friction and subsequently relieving painful arthritic symptoms.Hyaluronic acid for ophthalmic conditions and ophthalmological proceduresSolutions of hyaluronic acid with a concentration greater than .% moisturize the surface of the eyes to treat symptoms of dry eye while improving the stabilization of tear film, replenishing deficiencies of HA, reducing friction, and preventing binding of foreign substances to the ocular tissue.,Hyaluronic acid is frequently used during and after ophthalmological surgeries and plays important roles by virtue of its moisturizing, viscoelastic, and protective properties. It promotes tissue healing of the corneal epithelium and other parts of the eye following ophthalmological surgery, minimizing the risk of adhesions and free radical formation.TargetActionsOrganismACD antigenbinderHumansAIntercellular adhesion molecule inhibitorbinderHumansAHyaluronan mediated motility receptorbinderHumansUNeurocan core proteinbinderHumansUVersican core proteinbinderHumansUComplement component Q subcomponent-binding protein, mitochondrialbinderHumansUHyaluronan and proteoglycan link protein binderHumansUHyaluronan and proteoglycan link protein binderHumansUHyaluronan-binding protein binderHumansULayilinbinderHumansUStabilin-binderHumansUTumor necrosis factor-inducible gene proteinbinderHumansUInterphotoreceptor matrix proteoglycan binderHumansUIntracellular hyaluronan-binding protein binderHumansULymphatic vessel endothelial hyaluronic acid receptor Not AvailableHumans","['Dermal Filler', 'Promotion of wound healing', 'Synovial Fluid Lubrication']","['Adjuvants, Immunologic', 'Biocompatible Materials', 'Carbohydrates', 'Cicatrizants', 'Compounds used in a research, industrial, or household setting', 'Dermatologicals', 'Glycosaminoglycans', 'Immunologic Factors', 'Lubricants', 'Musculo-Skeletal System', 'Nasal Preparations', 'Ophthalmologicals', 'Polysaccharides', 'Preparations for Treatment of Wounds and Ulcers', 'Protective Agents', 'Sensory Organs', 'Surgical Aids', 'Viscoelastic Substances', 'Viscosupplements']" +DB01253,Ergometrine,Ergometrineis an ergot alkaloid used for the treatment of postpartum haemorrhage and post abortion hemorrhage in patients with uterine atony.,['P35348'],Ergonovine belongs to the group of medicines known as ergot alkaloids. These medicines are usually given to stop excessive bleeding that sometimes occurs after abortion or a baby is delivered. They work by causing the muscle of the uterus to contract.,[H][C@@]12CC3=CNC4=CC=CC(=C34)C1=C[C@H](CN2C)C(=O)N[C@@H](C)CO,"Ergonovine directly stimulates the uterine muscle to increase force and frequency of contractions. With usual doses, these contractions precede periods of relaxation; with larger doses, basal uterine tone is elevated and these relaxation periods will be decreased. Contraction of the uterine wall around bleeding vessels at the placental site produces hemostasis. Ergonovine also induces cervical contractions. The sensitivity of the uterus to the oxytocic effect is much greater toward the end of pregnancy. The oxytocic actions of ergonovine are greater than its vascular effects. Ergonovine, like other ergot alkaloids, produces arterial vasoconstriction by stimulation of alpha-adrenergic and serotonin receptors and inhibition of endothelial-derived relaxation factor release. It is a less potent vasoconstrictor than ergotamine. As a diagnostic aid (coronary vasospasm), ergonovine causes vasoconstriction of coronary arteries.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumans",[],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Alkaloids', 'Antidepressive Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Ergolines', 'Ergot Alkaloids and Derivatives', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'Reproductive Control Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Uterotonic agents']" +DB00939,Meclofenamic acid,"Meclofenamic acidis an NSAID used to treat mild to moderate pain, primary dysmenorrhea, heavy menstrual blood loss, rheumatoid arthritis, and osteoarthritis.","['P23219', 'P35354', 'P09917', 'O43526', 'O43525']","Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals.",CC1=C(Cl)C(NC2=CC=CC=C2C(O)=O)=C(Cl)C=C1,"The mode of action, like that of other nonsteroidal anti-inflammatory agents, is not known. Therapeutic action does not result from pituitary-adrenal stimulation. In animal studies, meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro meclofenamic acid was found to be an inhibitor of human leukocyte -lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamic acid. There is no evidence that meclofenamic acid alters the course of the underlying disease.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansAArachidonate -lipoxygenaseinhibitorHumansUPotassium voltage-gated channel subfamily KQT member otherHumansUPotassium voltage-gated channel subfamily KQT member otherHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Aminobenzoates', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzoates', 'Cyclooxygenase Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Fenamates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'OAT1/SLC22A6 inhibitors', 'ortho-Aminobenzoates', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Thyroxine-binding globulin substrates', 'Topical Products for Joint and Muscular Pain']" +DB04926,Neramexane,Neramexane is a low-to-moderate affinity uncompetitive NMDA receptor antagonist.,['Q8TCU5'],"Neramexane is similar to memantine and acetylcholinesterase inhibitors in that neramexane targets the cognitive decline in Alzheimer’s Disease by altering neurotransmitter signaling, but not the underlying pathological mechanisms that cause the disease (amyloid production or neurofibrillary tangle accumulation).",CC1(C)CC(C)(C)CC(C)(N)C1,"Neramexane is an uncompetitive NMDA receptor channel blocker.TargetActionsOrganismUGlutamate receptor ionotropic, NMDA ANot AvailableHumans",[],['Cycloparaffins'] +DB04888,Bifeprunox,"Bifeprunox is a novel atypical antipsychotic agent which, along with SLV313,aripiprazoleand SSR-181507 combines minimal D2 receptor agonism with 5-HT receptor agonism.","['P14416', 'P08908']","Bifeprunox is an atypical antipsychotic drug with mixed (agonist/antagonist) receptor activity with the neurotransmitters dopamine (D2/3/4) and serotonin. Bifeprunox differs from first-generation atypical antipsychotics in that it acts as a partial D2 agonist. This property is shared by aripiprazole, a drug already marketed in Europe and the US for treatment of schizophrenia. A placebo-controlled, dose-finding phase II trial in patients with schizophrenia showed that bifeprunox was both efficacious and well tolerated. Importantly, treatment with bifeprunox did not appear to cause some of the side effects seen with other atypicals agents in routine use, such as weight gain, hyperprolactinaemia and cardiotoxicity.",O=C1NC2=C(O1)C(=CC=C2)N1CCN(CC2=CC(=CC=C2)C2=CC=CC=C2)CC1,"In contrast to D receptor antagonism, partial D agonism is believed to decrease dopamine activity in an overactive dopamine system while simultaneously increasing dopamine activity in regions of the brain where dopaminergic activity is too low. By blocking overstimulated receptors and stimulating underactive ones, partial D agonists act as dopamine stabilisers. In common with aripiprazole, bifeprunox also acts as a serotonin, -HTA agonist. This property may contribute to efficacy against the negative symptoms of schizophrenia and reduce the likelihood of extrapyramidal symptoms (EPS).TargetActionsOrganismUDopamine D receptorNot AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumans",[],"['Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Neurotoxic agents']" +DB06800,Methylnaltrexone,Methylnaltrexoneis a μ-opioid antagonist used for the treatment of opioid-induced constipation in palliative patients that are inadequately responding to laxative therapy.,"['P35372', 'P41145']","Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested.",C[N@+]1(CC2CC2)CC[C@]23[C@H]4OC5=C(O)C=CC(C[C@@H]1[C@]2(O)CCC4=O)=C35,"Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract inhibit opioid-induced decrease in gastric motility and transit time. Because methylnaltrexone is a quaternary derivative of naltrexone, it produces its gastrointestinal effects without producing analgesic effects or withdrawal symptoms as it does not cross the blood-brain-barrier.TargetActionsOrganismAMu-type opioid receptorantagonistHumansNKappa-type opioid receptorantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Alkaloids', 'Amines', 'Ammonium Compounds', 'Central Nervous System Agents', 'Drugs for Constipation', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Miscellaneous GI Drugs', 'Morphinans', 'Nitrogen Compounds', 'Onium Compounds', 'Opiate Alkaloids', 'Opioid Antagonists', 'Opioids', 'Peripheral Nervous System Agents', 'Peripheral Opioid Receptor Antagonists', 'Phenanthrenes', 'Sensory System Agents']" +DB12278,Propiverine,Propiverineis an antimuscarinic agent used to treat urinary incontinence or increased urinary frequency or urgency.,"['P11229', 'P08172', 'P20309', 'P08912', 'Q13936', 'P35348', 'P08173']","Propiverine hydrochloride inhibits abnormal contractions of bladder smooth muscle in vivo through not only its anticholinergic activity but also its concurrent calcium antagonistic activity8. Through the above-mentioned mechanism, propiverine is able to relieve the symptoms of overactive bladder.In animal models, this administration of this drug leads to a dose-dependent decrease in intravesical pressure of the bladder and an increase in bladder capacity6. In patients with symptoms of OAB resulting from idiopathic detrusor muscle overactivity (IDO) or neurogenic detrusor overactivity (NDO), propiverine showed dose-dependent efficacy and tolerability1.",CCCOC(C(=O)OC1CCN(C)CC1)(C1=CC=CC=C1)C1=CC=CC=C1,"Propiverine demonstrates both anticholinergic and calcium-modulating properties. The efferent connection of the pelvic nerve is inhibited due to the anticholinergic action exerted by this drug, leading to relaxation of bladder smooth muscle. Propiverine blocks calcium ion influx and modulates the intracellular calcium in urinary bladder smooth muscle cells, resulting in the inhibition of muscle spasm. The bladder contains several muscarinic receptors. Acetylcholine is the main contractile neurotransmitter in the human bladder detrusor muscle, and antimuscarinics such as propiverine exert their effects by competitively inhibiting the binding of acetylcholine at muscarinic receptors on detrusor smooth muscle cells and other structures within the bladder wall. In one study, After oral treatment with propiverine, the bladder showed the highest concentration of M-, indicating a targeted distribution of this metabolite into the bladder. Therefore, muscarinic receptor- may highly contribute to the relatively selective and long-lasting occupation of bladder muscarinic receptors after oral ingestion of propiverine.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MNot AvailableHumansAVoltage-dependent L-type calcium channel subunit alpha-CantagonistHumansAAlpha-A adrenergic receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Acids, Carbocyclic', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Anticholinergic Agents', 'Autonomic Agents', 'Cholinergic Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Diphenylacetic Acids', 'Drugs for Urinary Frequency and Incontinence', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Hydroxy Acids', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Phenylacetates', 'Urological Agents', 'Urologicals']" +DB00854,Levorphanol,Levorphanolis an opioid analgesic used to treat moderate to severe pain.,"['P35372', 'P41143', 'P41145']","Levorphanol is a potent synthetic opioid analgesic indicated for the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate. Levorphanol is similar to morphine in its actions, however it is up to 8 times more potent than morphine. Levorphanol produces a degree of respiratory depression similar to that produced by morphine at equianalgesic doses, and like many mu-opioid drugs, levorphanol produces euphoria or has a positive effect on mood in many individuals.",[H][C@@]12CCCC[C@@]11CCN(C)[C@@H]2CC2=C1C=C(O)C=C2,Like other mu-agonist opioids it is believed to act at receptors in the periventricular and periaqueductal gray matter in both the brain and spinal cord to alter the transmission and perception of pain.TargetActionsOrganismAMu-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumans,[],"['Alkaloids', 'Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Narcotics', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00837,Progabide,"Progabide is an analog and prodrug of gamma-aminobutyric acid. It is commonly used in the treatment of epilepsy. It has agonistic activity for both the GABAA and GABAB receptors. In clinical trials, progabide has been investigated for Parkinson's disease, schizophrenia, clinical depression and anxiety disorder; its therapeutic effectiveness in these conditions is not fully elucidated.","['P14867', 'Q9UBS5']","Progabide, a fatty acid derivative, is a GABA receptor agonist used to treat the symptoms of epilepsy.",OC(=N)CCCN=C(C1=CC=C(Cl)C=C1)C1=C(O)C=CC(F)=C1,"Progabide binds to both GABAAand GABABreceptors located on the terminals of primary afferent fibers. Binding to GABAAresults in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Activation of the GABABreceptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGamma-aminobutyric acid type B receptor subunit agonistHumans",[],"['Acids, Acyclic', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Aminobutyrates', 'Anti-Dyskinesia Agents', 'Anti-Parkinson Drugs', 'Anticonvulsants', 'Antidepressive Agents', 'Butyrates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Fatty Acid Derivatives', 'GABA Agents', 'GABA Agonists', 'Nervous System', 'Neurotransmitter Agents', 'Psychotropic Drugs']" +DB06262,Droxidopa,"Droxidopais a medication used to treat symptomatic neurogenic orthostatic hypotension (nOH) caused by dopamine beta-hydroxylase deficiency, non-diabetic autonomic neuropathy and primary autonomic failure caused by conditions such as Parkinson's disease.","['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945', 'P00439']","Droxidopa is an orally active synthetic precursor of norepinephrine that increases the deficient supply of norepinephrine in patients with NOH, thereby improving orthostatic blood pressure and alleviating associated symptoms of lightheadedness, dizziness, blurred vision, and syncope through the induction of tachycardia (increased heart rate) and hypertension.",N[C@@H]([C@H](O)C1=CC(O)=C(O)C=C1)C(O)=O,Droxidopa crosses the blood-brain barrier where it is converted to norepinephrine via decarboxylation by L-aromatic-amino-acid decarboxylase. Norephinephrine acts at alpha-adrenergic receptors as a vasoconstrictor and at beta-adrenergic receptors as a heart stimulator and artery dilator.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-D adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-C adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansNPhenylalanine--hydroxylaseinhibitorHumans,[],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic and Dopaminergic Agents', 'Adrenergic beta-1 Receptor Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-3 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amines', 'Amino Acids', 'Amino Acids, Neutral', 'Amino Acids, Peptides, and Proteins', 'Anti-Dyskinesia Agents', 'Benzene Derivatives', 'Cardiac Stimulants Excl. Cardiac Glycosides', 'Cardiac Therapy', 'Catecholamines', 'Catechols', 'Central Nervous System Agents', 'Drugs that are Mainly Renally Excreted', 'Epinephrine and similars', 'Increased Blood Pressure', 'Phenols']" +DB05316,Pimavanserin,Pimavanserinis a second generation atypical antipsychotic used for the treatment of hallucinations and delusions caused by Parkinson's Disease.,"['P28223', 'P28335', 'Q99720']","Pimavanserin's unique actions on serotonin receptors improve symptoms of hallucinations and delusions associated with Parkinson's disease.2In clinical studies, 80.5% of individuals treated with pimavanserin reported improvement in symptoms. Pimavanserin does not worsen motor functioning in patients with Parkinson's disease psychosis.9In vitro, pimavanserin acts as an inverse agonist and antagonist at serotonin 5-HT2Areceptors with high binding affinity (Kivalue 0.087 nM) and at serotonin 5-HT2Creceptors with lower binding affinity (Kivalue 0.44 nM). Pimavanserin shows low binding to sigma 1 receptors (Kivalue 120 nM) and has no appreciable affinity (Kivalue >300 nM), to serotonin 5-HT2B, dopaminergic (including D2), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels.19The effect of pimavanserin on the QTc interval was evaluated in a randomized placebo- and positive-controlled double-blind, multiple-dose parallel thorough QTc study in 252 healthy subjects. A central tendency analysis of the QTc data at steady-state demonstrated that the maximum mean change from baseline (upper bound of the two-sided 90% CI) was 13.5 (16.6) msec at a dose of twice the therapeutic dose. A pharmacokinetic/pharmacodynamic analysis with pimavanserin suggested a concentration-dependent QTc interval prolongation in the therapeutic range.19In the 6-week, placebo-controlled effectiveness studies, mean increases in QTc interval of ~5-8 msec were observed in patients receiving once-daily doses of pimavanserin 34 mg. These data are consistent with the profile observed in a thorough QT study in healthy subjects. Sporadic QTcF values ≥500 msec and change from baseline values ≥60 msec were observed in subjects treated with pimavanserin 34 mg; although the incidence was generally similar for pimavanserin and placebo groups. There were no reports of torsade de pointes or any differences from placebo in the incidence of other adverse reactions associated with delayed ventricular repolarization in studies of pimavanserin, including those patients with hallucinations and delusions associated with Parkinson’s disease psychosis.19",CC(C)COC1=CC=C(CNC(=O)N(CC2=CC=C(F)C=C2)C2CCN(C)CC2)C=C1,"Parkinson's disease psychosis (PDP) is an imbalance of serotonin and dopamine from disruption of the normal balance between the serotonergic and dopaminergic receptors and neurotransmitters in the brain.The mechanism by which pimavanserin treats hallucinations and delusions associated with Parkinson’s disease psychosis is not fully established. It is possible that pimavanserin acts via inverse agonist and antagonist activity at serotonin -HTAreceptors with limited effects on serotonin -HTCreceptors. Pimavanserin is an inverse agonist and antagonist of serotonin -HTAreceptors with high binding affinity, demonstrating low binding affinity to serotonin -HTCreceptors. In addition, this drug exhibits low affinity binding to sigma receptors.Pimavanserin lacks activity at muscarinic, dopaminergic, adrenergic, and histaminergic receptors, preventing various undesirable effects typically associated with antipsychotics.TargetActionsOrganismA-hydroxytryptamine receptor Ainverse agonistHumansU-hydroxytryptamine receptor Cinverse agonistHumansUSigma non-opioid intracellular receptor binderHumans",[],"['Amides', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Psycholeptics', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB11186,Pentoxyverine,"Pentoxyverineis a medication used to suppress a cough in the common cold, flu, bronchitis, and sinusitis.","['Q99720', 'Q12809', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'P41145', 'P35372']","Pentoxyverine induces an antitussive action. In animal studies, intraperitoneal administration of pentoxyverine inhibited citric-acid-induced cough in guinea-pigsin vivo2. Some mice and rat studies suggest that pentoxyverine may also exert anticonvulsant activities without inducing a protective effect from NMDA-induced lethality4,5. Protective effects against maximal electroshock-induced seizures in a dose-related fashion was also observed following either intraperitoneal or oral administration5. In hERG-transfected cells, pentoxyverine inhibited the outward current of the hERG ion channel with half-maximal inhibition concentrations (IC50) of 3.0 µM3. In rats receiving intrathecal administration, pentoxyverine exhibited dose-dependent spinal blockade with a more sensory-selective action over motor blockade6. It induced a spinal blockade with a more sensory/nociceptive-selective action over motor blockade compared to lidocaine6.",CCN(CC)CCOCCOC(=O)C1(CCCC1)C1=CC=CC=C1,"While the mechanism of antitussive action of pentoxyverine is not fully understood, it is thought to be mediated via sigma- receptors expressed in the central nervous system. Pentoxyverine acts as an agonist at sigma receptors with the Ki of ± nM, as demonstrated in a competitive binding assay. The function of sigma receptors on cough suppressant activities is unclear, however these receptors are highly expressed in the nucleus tractus solitarius (NTS) of the brainstem where the afferent fibres first synapse. NTS is located very close to the cough centre in the brainstem thus may function as a ‘gate' for the cough reflex and allow sigma- receptor agonists to modulate afferent activity prior to reaching the cough center. It is suggested that highly lipophilic sigma- agonists may penetrate the CNS following systemic administration. When administered as aerosols, sigma- receptor agonists may temporarily act in the periphery to modulate cough by acting activate sigma receptors expressed in the lungs. However there is limited evidence of peripheral localization of the sigma agonists following aerosol administration and the ruling out of systemic exposure. The local anesthesia action of pentoxyverine may occur through inhibition of voltage-gated Na(+) currents.TargetActionsOrganismASigma non-opioid intracellular receptor agonistHumansUPotassium voltage-gated channel subfamily H member inhibitorHumansUVoltage-gated sodium channel alpha subunitinhibitorHumansUKappa-type opioid receptoragonistHumansUMu-type opioid receptorantagonistHumans",[],"['Antitussive Agents', 'Central Nervous System Agents', 'Cough and Cold Preparations', 'Cycloparaffins', 'Respiratory System Agents']" +DB09238,Manidipine,Manidipineis a dihydropyridine calcium channel blocker used to treat hypertension.,"['Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555', 'O43497', 'O95180', 'Q9P0X4', 'O43497', 'O95180', 'Q9P0X4']",Manidipine produces vasodilation resulting in lower blood pressure1.,COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)N(=O)=O)C(=O)OCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1,"Contraction of vascular smooth muscle is stimulated by Gq coupled receptors which produce calcium release from the sarcoplasmic reticulum. This is followed by opening of voltage dependent calcium channels and an influx of calcium into the cell ultimately producing contraction. Manidipine binds to and dissociates slowly from L- and T-type voltage dependent calcium channels on smooth muscle cells, blocking the entrance of extracellular calcium into the cell and preventing this contraction,. This produces vasodilation which decreases blood pressure. Manidipine produces renal vasodilation and an increase in natriuresis. This likely contributes to the antihypertensive effect by reducing blood volume. Manidipine is selective for the vasculature and does not produce significant effects on the heart or central nervous system at clinically relevant dosages.TargetActionsOrganismAVoltage-dependent L-type calcium channelblockerHumansAVoltage-dependent T-type calcium channelinhibitorblockerHumansUVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Benzene Derivatives', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Membrane Transport Modulators', 'Nitro Compounds', 'Pyridines', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00403,Ceruletide,"Caerulein is a specific decapeptide similar in action and composition to the natural gastrointestinal peptide hormone cholecystokinin. It exerts stimulatory effects on the gastric, biliary, and pancreatic secretion, as well as on certain smooth muscles.",['P32238'],"Caerulein is a specific decapeptide similar in action and composition to the natural gastrointestinal peptide hormone cholecystokinin that stimulates gastric, biliary, and pancreatic secretion. It also exerts stimulatory actions on certain smooth muscles.",[H][C@](NC(=O)[C@H](CC1=CC=C(OS(O)(=O)=O)C=C1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCC(=O)N1)([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(N)=O,"Caerulein acts according to its similarity to the natural gastrointestinal peptide hormone cholecystokinin. Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin is secreted by the duodenum, the first segment of the small intestine. There it binds to CCK receptors, activating them and causing downstream effects. Specifically, it results in the release of digestive enzymes and bile from the pancreas and gall bladder, respectively. It also acts as a hunger suppresant. Cholecystokinin is secreted by the duodenum when fat- or protein-rich chyme leaves the stomach and enters the duodenum. The hormone acts on the pancreas to stimulate the secretion of the enzymes lipase, amylase, trypsin, and chymotrypsin. Together these pancreatic enzymes catalyze the digestion of fat and protein. Cholecystokinin also stimulates both the contraction of the gall bladder, and the relaxtion of the Sphincter of Oddi (Glisson's Sphinctor), which delivers, (not secretes) bile into the small intestine. Bile salts serve to emulsify fats, thereby increasing the effectiveness with which enzymes can digest them.TargetActionsOrganismACholecystokinin receptor type AinducerHumans",[],"['Amino Acids, Peptides, and Proteins', 'Diagnostic Agents', 'Oligopeptides', 'Peptides', 'Tests for Bile Duct Patency']" +DB06694,Xylometazoline,Xylometazolineis a direct-acting alpha-adrenergic agonist used for the symptomatic treatment of nasal congestion and minor inflammation due to allergies or colds.,"['P08913', 'P18089', 'P35348', 'P35368', 'P25100', 'P18825']","Xylometazoline is a sympathomimetic agent that causes vasoconstriction of the nasal mucosa. In one study comprising subjects with nasal congestion associated with the common cold, the median time of onset of subjective relief of nasal congestion was about 1.7 minutes and the time of subjective peak relief of nasal congestion was 30 minutes.2Previous studies reported rebound swelling, rebound nasal congestion, rhinitis medicamentosa, and shorter duration of decongestant effect from the long-term use of xylometazoline in healthy volunteers, suggesting that the drug is most effective if used temporarily.2,3An earlyin vitrostudy demonstrated xylometazoline to exert anti-oxidant actions, where it inhibited microsomal lipid peroxidation and mediated hydroxyl radical scavenging activity. This suggests that xylometazoline has a beneficial effect against oxidants, which play a role in tissue damage in inflammation.8",CC1=CC(=CC(C)=C1CC1=NCCN1)C(C)(C)C,"Nasal congestion is caused by various etiologies, such as rhinosinusitis and allergic or non-allergic rhinitis, leading to congestion of the venous sinusoids lining the nasal mucosa. Activation of α-adrenergic receptors leads to vasoconstriction of the blood vessels of the nasal mucosa and resumption of nasal airflow.As the most abundantly expressed in the human nasal mucosa, αA- and αB-adrenoceptors may play the most important role in vasoconstriction of the human nasal mucosa. Xylometazoline is a more selective agonist at αB-adrenoceptors,,with affinity at αA-, αA-, αC-, αB-, and αD-adrenoceptors.Xylometazoline decreases nasal resistance during inspiration and expiration and increases the volume of nasal airflow. Compared tooxymetazoline, another imidazoline nasal decongestant, xylometazoline had a slightly faster onset of action although they had a similar duration of action.In one study, subjects with nasal congestion reported relief of earache and sore throat in addition to nasal decongestion: it is speculated that oxymetazoline mediates this effect by causing vasoconstriction of the nasal mucosa that contains the venous sinuses and nasal decongestion allows breathing through the nose, providing relief from sore throat caused by mouth breathing that dries and irritates the throat.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistpartial agonistHumansUAlpha-B adrenergic receptoragonistHumansUAlpha-D adrenergic receptoragonistHumansUAlpha-C adrenergic receptoragonistHumans",[],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Antiarrhythmic agents', 'Antihistamine Drugs', 'Calcium Channel Blockers', 'Cardiovascular Agents', 'Decongestants and Antiallergics', 'Nasal Decongestants', 'Nasal Preparations', 'Ophthalmologicals', 'Respiratory System Agents', 'Sensory Organs', 'Sympathomimetics Used as Decongestants', 'Sympathomimetics, Plain', 'Vasoconstrictor Agents', 'Vasodilating Agents']" +DB09304,Setiptiline,"Setiptiline is a tetracyclic antidepressant (TeCA) which acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). In Japan, the company Mochida started its commercialization for the treatment of depression started in 1989.","['P08913', 'P18089', 'P18825', 'P08908', 'P28222', 'P28221', 'P28566', 'P30939', 'P28223', 'P41595', 'P28335', 'P46098', 'O95264', 'Q8WXA8', 'Q70Z44', 'A5X5Y0', 'Q13639', 'P50406', 'P34969']",Setiptiline is a tertacyclic antidepressant4. It acts to reduce the symptoms of major depressive disorder.,CN1CCC2=C(C1)C1=CC=CC=C1CC1=CC=CC=C21,"Setiptiline is an antagonist at the α adrenergic receptor and at serotonin receptors,. The antagonism of the α receptors likely relieves presynaptic inhibition of adrenergic neurotransmission, allowing for greater and longer sustained release of noradrenaline into the synapse. The antagonism of serotonin receptors may produce an upregulation of the receptors leading to an eventual increase in serotonergic signalling. The actual physiological mechanisms behind the antidepressant effect of setiptiline is unknown but the listed possibilities exist as likely explanations.TargetActionsOrganismUAlpha- adrenergic receptorsantagonistHumansUSerotonin ReceptorsantagonistHumans",[],"['Antidepressive Agents, Tetracyclic', 'Dibenzazepines', 'Heterocyclic Compounds, Fused-Ring']" +DB01367,Rasagiline,Rasagilineis an irreversible inhibitor of monoamine oxidase used for the symptomatic management of idiopathic Parkinson's disease as initial monotherapy and as adjunct therapy to levodopa.,"['P27338', 'P10415']","Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications.",C#CCN[C@@H]1CCC2=CC=CC=C12,"The precise mechanisms of action of rasagiline is unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline's beneficial effects seen in models of dopaminergic motor dysfunction.TargetActionsOrganismAAmine oxidase [flavin-containing] BinhibitorHumansAApoptosis regulator Bcl-activatorHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hypotensive Agents', 'Indenes', 'Monoamine Oxidase B Inhibitors', 'Monoamine Oxidase Inhibitors', 'Nervous System', 'Neuroprotective Agents', 'Protective Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators']" +DB01622,Thioproperazine,"Thioproperazineis an antipsychotic indicated for the management of acute and chronic schizophrenia, including cases that are refractory to more common neuroleptics. May also be used to treat manic syndromes.","['P14416', 'P35348', 'P35368', 'P21728']","Thioproperazine is a potent neuroleptic with antipsychotic properties. Thioproperazine has a marked cataleptic and antiapomorphine activity associated with relatively slight sedative, hypothermic and spasmolytic effects. It is virtually without antiserotonin and hypotensive action and has no antihistaminic property.",CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3N2CCCN2CCN(C)CC2)C=C1,"Thioproperazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D, D, D and D - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (-HT and -HT, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha/alpha-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M/M-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).TargetActionsOrganismADopamine D receptorantagonistHumansAAlpha-A adrenergic receptorantagonistHumansAAlpha-B adrenergic receptorantagonistHumansUDopamine D receptorantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Depressants', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Phenothiazines', 'Phenothiazines With Piperazine Structure', 'Psycholeptics', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds']" +DB08908,Dimethyl fumarate,Dimethyl fumarateis a medication used to treat patients with the relapsing-remitting form of multiple sclerosis.,"['Q14145', 'Q04206']","The physiological effects of dimethyl fumarate on the body are not well understood. It has anti-inflammatory and cytoprotective effects, likely involved in its actions in multiple sclerosis (MS) patients.3Dimethyl fumarate does not cause clinically significant QT interval prolongation. However, cases of progressive multifocal leukoencephalopathy, serious opportunistic infections, lymphopenia and liver injury have been reported in MS patients treated with this drug. Dimethyl fumarate may also cause anaphylaxis and angioedema.4",[H]\C(=C(\[H])C(=O)OC)C(=O)OC,"The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite, monomethyl fumarate (MMF). Both dimethyl fumarate and MMF up-regulate the Nuclear factor (erythroid-derived )-like (Nrf) pathway that is activated in response to oxidative stress. Dimethyl fumarate also suppresses pro-inflammatory genes through nuclear factor kappa B inhibition. Additionally, MMF acts as an agonist at the nicotinic acid receptor, but the relevance of this is unknown.,It has been suggested that dimethyl fumarate exerts its immunomodulatory effects through changes in the composition and phenotype of immune cells. It reduces CNS infiltration and alters the composition of all lymphocyte subpopulations, especially for cytotoxic and effector T cells. This causes a shift from a mainly pro-inflammatory phenotype to an anti-inflammatory one.TargetActionsOrganismAKelch-like ECH-associated protein binderHumansUTranscription factor pinhibitorbinderHumans",[],"['Acids, Acyclic', 'Anti-Inflammatory Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytoprotective Agent', 'Dermatologicals', 'Dicarboxylic Acids', 'Fumarates', 'Immunologic Factors', 'Immunomodulatory Agents', 'Immunosuppressive Agents', 'Miscellaneous Central Nervous System Agents', 'Radiation-Sensitizing Agents']" +DB08899,Enzalutamide,Enzalutamideis a second-generation androgen receptor inhibitor used to treat castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer.,['P10275'],"Enzalutamide is a second-generation antiandrogen that blocks the activity of androgen and androgen receptor (AR) in prostate cancer. AR activity and prostate cancer progression are closely related due to the normal physiology of prostate cells, providing the rationale for androgen deprivation therapy (ADT).4However, resistance will eventually arise after the commencement of ADT in 2-3 years due to the accumulation of mutations, including constitutively active mutation, AR overexpression, and changes in AR splicing variants.5,1Enzalutamide was therefore designed to exploit these mutations.3In vitro experiments in human prostate cancer cell line VCaP showed that enzalutamide can suppress cell growth and induce apoptosis while other antiandrogens like bicalutamide did not.3Clinical trials on prostate cancer patients indicated that enzalutamide can lead to a decrease in serum PSA for at least 12 weeks, although this response can be short-lived and thus resulting in enzalutamide resistance.6,3Patients receiving enzalutamide also had a 37% decreased in the risk of death compared to placebo.2",CNC(=O)C1=C(F)C=C(C=C1)N1C(=S)N(C(=O)C1(C)C)C1=CC=C(C#N)C(=C1)C(F)(F)F,"Enzalutamide is a competitive androgen receptor (AR) inhibitor that has a threefold inhibition on the androgen signaling pathway without significant AR agonist activity.,It inhibits androgen binding to its receptor, androgen receptor nuclear translocation, and subsequent interaction with chromosomal DNA to upregulate oncogenes.,Enzalutamide binds to the AR with to -fold greater affinity than first-generation antiandrogens such as bicalutamide and only - fold reduced affinity than the natural ligand dihydrotestosterone.Molecular docking showed that enzalutamide binds to the ligand binding domain of the AR distinctive from that of bicalutamide.TargetActionsOrganismAAndrogen receptorinhibitorHumans",[],"['Amides', 'Androgen Receptor Antagonists', 'Androgen Receptor Inhibitors', 'Antiandrogens', 'Antiandrogens, non-steroidal', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Benzene Derivatives', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (moderate)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Hormone Antagonists and Related Agents', 'Hydantoins', 'Imidazoles', 'Imidazolidines', 'P-glycoprotein inhibitors', 'Thyroxine-binding globulin substrates']" +DB01602,Bacampicillin,"Bacampicillinis an ampicillin prodrug used to treat various susceptible bacterial infections in the body, such as respiratory infections and skin and subcutaneous tissue infections.","['P0AEB2', 'P24228', 'P08506', 'P02918', 'P02919', 'P0AD65', 'P0AD68']",Bacampicillin is a prodrug of ampicillin and is microbiologically inactive.,[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(=O)OC(C)OC(=O)OCC,"During absorption from the gastrointestinal tract, bacampicillin is hydrolyzed by esterases present in the intestinal wall. It is microbiologically active as ampicillin, and exerts a bactericidal action through the inhibition of the biosynthesis of cell wall mucopeptides.TargetActionsOrganismAPenicillin-binding proteininhibitorGram positive and gram negative bacteria",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00792,Tripelennamine,"Tripelennamineis a histamine H1 antagonist used to treat hypersensitivity reactions, coughs, and the common cold.",['P35367'],"Used to treat the effects of colds and allergies. Tripelennamine is an antihistamine. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Tripelennamine is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",CN(C)CCN(CC1=CC=CC=C1)C1=CC=CC=N1,"Tripelennamine binds to the histamine H receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Amines', 'Aminopyridines', 'Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Antihistamines for Topical Use', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Diamines', 'Ethylenediamine Derivatives', 'Ethylenediamines', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Polyamines', 'Pyridines', 'Substituted Ethylene Diamines']" +DB00427,Triprolidine,"Triprolidineis a sedating antihistamine combined with pseudoephedrine and guaifenesin in various types of cold and allergy medications to relieve allergy symptoms, hay fever and common cold symptoms, and to aid in sleep.",['P35367'],"In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Triprolidine, is a histamine H1 antagonist that competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. Triprolidine has anticholinergic and sedative effects.",CC1=CC=C(C=C1)C(=C/CN1CCCC1)\C1=CC=CC=N1,"Triprolidine binds to the histamine H receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Central Nervous System Depressants', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents']" +DB00484,Brimonidine,"Brimonidineis an alpha-2 adrenergic agonist used to treat glaucoma and ocular hypertension, as well as facial erythema in rosacea.","['P08913', 'P18089', 'P18825']","Brimonidine is a highly selective alpha-2 adrenergic receptor agonist that is 1000-fold more selective for the alpha2-adrenergic receptor than the alpha1-adrenergic receptor.15This characteristic gives the drug some therapeutic advantages, since it reduces the risk of systemic side effects, such as systemic hypotension, bradycardia, and sedation. In addition, there is a reduction in the risk for developing alpha-1 mediated ocular unwanted effects, such as conjunctival blanching, mydriasis, and eyelid retraction.11However, despite high alpha-2 receptor specificity, brimonidine may still produce alpha-1 adrenoceptor-mediated ocular effects, such as conjunctival vasoconstriction.6Brimonidine has a peak ocular hypotensive effect occurring at two hours post-dosing.LabelIn a randomized, double-blind clinical study, ocular administration of 0.2% brimonidine in healthy volunteers resulted in a 23% reduction of mean intraocular pressure from baseline at 3 hours following administration.3In comparative studies consisting of patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive effect of brimonidine was maintained during treatment periods of up to 1 year.1Brimonidine mediates vasoconstrictive effects and it was shown to exhibit anti-inflammatory properties inex vivohuman skin model andin vivoinflammation models.12In a clinial trials consisting of adults with moderate to severe facial erythema of rosacea, brimonidine was shown to improve the extent of redness at 3 hours after application, compared to placebo.15It was shown to be a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200 µm. Inin vivomouse inflammation models, brimonidine displayed anti-inflammatory properties by inhibiting edema.8In a randomized, double-blind study, brimonidine reduced erythema for the 12 hours of the study in a dose-dependent manner.8When adminsitered systemically, brimonidine was shown to cause cardiovascular effects by decreasing blood pressure, decreasing heart and respiratory rate, and prolonging the PR interval in the electrocardiogram. This is due to the targeting of adrenoceptors by the drug.4,5Although the clinical significance has not been established, there is evidence that brimonidine exhibits neuroprotective activity in experimental models of cerebral ischemia and optic nerve injury.6In vitrostudies show that brimonidine mediated protective effects on neuronal cells from kainate acid insult and on cultured retinal ganglion cells from glutamate-induced cytotoxicity, which is a possible mediator of secondary neuronal degeneration in human glaucoma. Neuroprotective actions of brimonidine were also demonstrated in rat models of acute retinal ischemia and chronic IOP elevation. It has been proposed that brimonidine may exert neuroprotective effects on the retina and optic nerve by enhancing intrinsic retinal ganglion cell survival mechanisms and/or induction of neuronal survival factors, such as bFGF.3However, further investigations are needed to conclude on these possible therapeutic benefits of the drug.",BrC1=C(NC2=NCCN2)C=CC2=NC=CN=C12,"In the eye, alpha- adrenoceptors play a role in vasoconstriction, mydriasis, eyelid retraction, and elevation of intraocular pressure (IOP) whereas alpha- adrenoceptors are responsible for IOP reduction via a complex Gi-coupled signaling cascade pathway. Activation of alpha- receptors leads to inhibition of adenylyl cyclase and reduction of cyclic AMP levels. As a result, there is a decrease in norpinephrine (NE) release at the synaptic junction, NE-induced stimulation of beta- adrenoceptors, and production of aqueous humor by the ciliary epithelium.An elevated IOP is the most significant risk factor for developing glaucomatous optic neuropathy, which is associated with progressive visual field loss and functional disability if left untreated.Regardless of the etiology of the disease, the aim of current therapies for glaucoma is to reduce IOP, as reduction of IOP significantly reduces the risk of progression of vision loss even when IOP is already within the normal range.When administered ophthalmically, brimonidine is rapidly absorbed into the eye, acts as an agonist at ocular alpha- adrenoceptors and lowers IOP via a dual mechanism of action.It is proposed that initial dosing of the drug causes a reduction in aqueous humour production and chronic dosing leads to an increase in uveoscleral outflow.Brimonidine does not affect episcleral venous pressure.By reducing IOP, brimonidine aims to reduce the likelihood of glaucomatous visual field loss in ocular hypertension, and slow the progression of visual field defect in established open-angle glaucoma.When applied topically on skin, brimonidine reduces erythema through direct vasocontriction of small arteries and veins.As brimonidine mediates a potent peripheral vasoconstrictive activity by selectively working on the alpha- adrenoceptors, the use of brimonidine is thought to be efficacious for the treatment of facial erythema of rosacea, which is thought to arise from vasomotor instability and abnormal vasodilation of the superficial cutaneous vasculature of the face.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-B adrenergic receptoragonistHumansAAlpha-C adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Antiglaucoma Preparations and Miotics', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Decongestants and Antiallergics', 'Dermatologicals', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Misc. Skin and Mucous Membrane Agents', 'Ophthalmologicals', 'Quinoxalines', 'Sensory Organs', 'Sympathomimetics in Glaucoma Therapy', 'Sympathomimetics Used as Decongestants']" +DB01073,Fludarabine,Fludarabineis a purine analog antimetabolite that inhibits DNA synthesis.,"['P27707', 'P09884', 'P23921']","Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.",NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O,"Fludarabine phosphate is rapidly dephosphorylated to -fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, -fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.TargetActionsOrganismADNAincorporation into and destabilizationHumansADeoxycytidine kinaseagonistHumansADNA polymerase alpha catalytic subunitinhibitorHumansARibonucleoside-diphosphate reductase large subunitinhibitorHumans",[],"['Adenine Nucleotides', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Arabinonucleosides', 'Arabinonucleotides', 'Cardiotoxic antineoplastic agents', 'DNA (Cytosine-5-)-Methyltransferases, antagonists & inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Immunologic Factors', 'Immunosuppressive Agents', 'Myeloablative Agonists', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'Nucleotides', 'Purine Analogues', 'Purine Nucleosides', 'Purine Nucleotides', 'Purines', 'Toxic Actions']" +DB01437,Glutethimide,Glutethimide is a hypnotic and sedative. Its use has been largely superseded by other drugs.,"['P14867', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","Glutethimide, like the barbiturates, is a hypnotic sedative. It was introduced in 1954 as a safer alternative to barbiturates but was soon determined to be just as likely to cause addiction and withdrawal symptoms.",CCC1(CCC(=O)NC1=O)C1=CC=CC=C1,"Glutethimide seems to be a GABA agonist which helps induce sedation. It also induces CYP D. When taken with codeine, it enables the body to convert higher amounts of codeine (higher than the average - %) to morphine. This combination of effects enhances sedation.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-agonistHumansAGABA(A) Receptorpositive allosteric modulatorHumans",[],"['Central Nervous System Agents', 'Central Nervous System Depressants', 'Hypnotics and Sedatives', 'Nervous System', 'Piperidinedione Derivatives', 'Piperidines', 'Piperidones', 'Psycholeptics']" +DB03880,Batimastat,Not Available,"['Q9UKQ2', 'Q9UNA0', 'P22894', 'P39900', 'P51512']",An anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. Batimastat is a matrix metalloproteinase inhibitor.,[H][C@@](CC1=CC=CC=C1)(NC(=O)[C@]([H])(CC(C)C)[C@]([H])(CSC1=CC=CS1)C(=O)NO)C(=O)NC,TargetActionsOrganismUDisintegrin and metalloproteinase domain-containing protein Not AvailableHumansUA disintegrin and metalloproteinase with thrombospondin motifs Not AvailableHumansUNeutrophil collagenaseNot AvailableHumansUMacrophage metalloelastaseNot AvailableHumansUMatrix metalloproteinase-Not AvailableHumans,[],"['Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Antineoplastic Agents', 'Enzyme Inhibitors', 'Metalloendopeptidases, antagonists & inhibitors', 'Protease Inhibitors', 'Sulfur Compounds']" +DB00217,Bethanidine,A guanidinium antihypertensive agent that acts by blocking adrenergic transmission.,"['P48048', 'P08913', 'P18089', 'P18825', 'P08588', 'P07550', 'P13945']","Bethanidine is a guanidinium antihypertensive agent that acts by blocking adrenergic transmission. The precise mode of action is not clear. Although bethanidine may produce adverse effects, they are beneficial in severe hypertension and produce fewer side effects than guanethidine.",CN\C(NCC1=CC=CC=C1)=N/C,"Bethanidine, a guanidine derivative, is a peripherally acting antiadrenergic agent which primarily acts as an alphaa adrenergic agonist. Bethanidine effectively decreases blood pressure by suppressing renin secretion or interfering with function of the sympathetic nervous system.TargetActionsOrganismAATP-sensitive inward rectifier potassium channel inhibitorHumansAAlpha- adrenergic receptorsagonistHumansUBeta adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amidines', 'Antiadrenergic Agents, Peripherally Acting', 'Antihypertensive Agents', 'Autonomic Agents', 'Cardiovascular Agents', 'Guanidine Derivatives', 'Guanidines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Sympatholytics']" +DB04840,Debrisoquine,An adrenergic neuron-blocking drug similar in effects to guanethidine. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.,['P23975'],Debrisoquin is an adrenergic neuron-blocking drug similar in effects to guanethidine. It is a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.,NC(=N)N1CCC2=CC=CC=C2C1,"Debrisoquin acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine, rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters. It becomes concentrated in NE transmitter vesicles, replacing NE in these vesicles. This leads to a gradual depletion of NE stores in the nerve endings. Once inside the terminal it blocks the release of noradrenaline in response to arrival of an action potential. In contrast to ganglionic blocking agents, debrisoquin suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, debrisoquin lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.TargetActionsOrganismASodium-dependent noradrenaline transporterinducerHumans",[],"['Adrenergic Agents', 'Antiadrenergic Agents, Peripherally Acting', 'Antihypertensive Agents', 'Autonomic Agents', 'Cardiovascular Agents', 'Catecholamines', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Guanidine Derivatives', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Peripheral Nervous System Agents', 'Sympatholytics']" +DB00691,Moexipril,Moexiprilis an angiotensin converting enzyme inhibitor prodrug used to treat hypertension.,['P12821'],"Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.",CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC(OC)=C(OC)C=C2C[C@H]1C(O)=O,"Moexipril is a prodrug for moexiprilat, which inhibits ACE in humans and animals. The mechanism through which moexiprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of the inactive decapeptide angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates aldosterone secretion by the adrenal cortex and provides negative feedback on renin secretion. ACE is identical to kininase II, an enzyme that degrades bradykinin, an endothelium-dependent vasodilator. Moexiprilat is about times as potent as moexipril in inhibiting ACE and kininase II. Inhibition of ACE results in decreased angiotensin II formation, leading to decreased vasoconstriction, increased plasma renin activity, and decreased aldosterone secretion. The latter results in diuresis and natriuresis and a small increase in serum potassium concentration (mean increases of about . mEq/L were seen when moexipril was used alone). Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of moexipril remains to be elucidated. Although the principal mechanism of moexipril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect on blood pressure even in apparent low-renin hypertension.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['ACE Inhibitors and Diuretics', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Isoquinolines', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Protease Inhibitors', 'QTc Prolonging Agents']" +DB06712,Nilvadipine,Nilvadipineis a calcium channel blocker used to manage arterial hypertension.,"['Q13936', 'P54289', 'Q08289', 'Q01668', 'Q13698', 'Q8IZS8', 'O95180', 'Q9P0X4', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O43497', 'O95180', 'Q9P0X4']","Nilvadipine is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. Nilvadipine is used to treat Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure.",COC(=O)C1=C(NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)C)C#N,"Nilvadipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CinhibitorHumansAVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansAVoltage-dependent L-type calcium channel subunit beta-inhibitorHumansUVoltage-dependent L-type calcium channel subunit alpha-DinhibitorHumansUVoltage-dependent L-type calcium channel subunit alpha-SinhibitorHumansUVoltage-dependent calcium channel subunit alpha-/delta-inhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-IinhibitorHumansUVoltage gated L-type calcium channelblockerHumansUVoltage-dependent T-type calcium channelinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB05229,Beraprost,"Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.",['P43119'],"Beraprost is a stable, orally active prostacyclin analogue with vasodilatory, antiplatelet and cytoprotective effects. Beraprost is generally well tolerated and appears to be an effective agent in the treatment of patients with Buerger's disease and arteriosclerosis obliterans. Comparative data from a large randomised trial indicated that the drug appears as effective as ticlopidine in patients with these conditions. In patients with intermittent claudication, significant benefits of beraprost compared with placebo were reported in a randomised clinical trial; however, the use of beraprost in these patients is not supported by recent preliminary unpublished data from a large, phase III, placebo-controlled study. Limited data suggest some efficacy with long-term beraprost treatment of patients with PAH, where options are few and where oral administration of the drug could be a considerable advantage over intravenous prostacyclin (PGI2) therapy.",[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)C(C)CC#CC)[C@@]1([H])C1=C(O2)C(CCCC(O)=O)=CC=C1,Beraprost acts by binding to prostacyclin membrane receptors ultimately inhibiting the release of Ca+from intracellular storage sites. This reduction in the influx of Ca+has been postulated to cause relaxation of the smooth muscle cells and vasodilation.TargetActionsOrganismUProstacyclin receptorNot AvailableHumans,[],"['Anticoagulants', 'Antiplatelet agents', 'Autacoids', 'Biological Factors', 'Blood and Blood Forming Organs', 'Cardiovascular Agents', 'Cryoprotective Agents', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 Substrates', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Hematologic Agents', 'Inflammation Mediators', 'Lipids', 'Platelet Aggregation Inhibitors Excl. Heparin', 'Prostacyclin Analogues', 'Prostaglandins', 'Prostaglandins I', 'Vasodilating Agents']" +DB08814,Triflusal,Triflusalis a medication related to acetylsalicylic acid with antithrombotic effects used in the treatment of thromboembolic diseases.,"['P23219', 'P19838', 'P35228', 'Q9Y233']","Triflusal is an antithrombotic anticoagulant. It irreversibly inhibits the production of thromboxane-B2 in platelets by acetylating cycloxygenase-1. Triflusal affects many other targets such as NF kappa B, which is a gene expression regulatory factor for cycloxygenase-a and cytokines. Numerous studies comparing the efficacy and safety profile (i.e. systemic hemorrhage) between triflusal and acetylsalsylic acid has shown either no significant difference or a better effacy and safety profile for triflusal. Triflusal has been shown to protect cerebral tissue due to its inhibition of lipid peroxidation resulting from anoxia-reoxygenation.1",CC(=O)OC1=C(C=CC(=C1)C(F)(F)F)C(O)=O,"Triflusal is chemically related to acetylsalicylic acid (ASA) and irreversibly inhibits cycloxygenase- (COX-) in platelets. Acetylation of the active group of COX- prevents the formation of thromboxane-B in platelets. However, it is unique because it spares the arachidonic acid metabolic pathway in endothelial cells. In addition, it favors the production of nitric oxide, a vasodilator.TargetActionsOrganismAProstaglandin G/H synthase antagonistHumansANuclear factor NF-kappa-B p subunitantagonistHumansANitric oxide synthase, inducibleagonistHumansAcAMP and cAMP-inhibited cGMP ','-cyclic phosphodiesterase AantagonistHumans",[],"['Acids, Carbocyclic', 'Anticoagulants', 'Antiplatelet agents', 'Benzene Derivatives', 'Benzoates', 'Blood and Blood Forming Organs', 'Hematologic Agents', 'Hydroxy Acids', 'Hydroxybenzoates', 'Phenols', 'Platelet Aggregation Inhibitors Excl. Heparin']" +DB00685,Trovafloxacin,Trovafloxacinis an antibiotic used to treat gonorrhea and chlamydia.,"['P43700', 'P43702', 'P11388']","Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin in vitro develops slowly via multiple-step mutation in a manner similar to other fluoroquinolones. Resistance to trovafloxacin in vitro occurs at a general frequency of between 1x10-7to 10-10. Although cross-resistance has been observed between trovafloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to trovafloxacin.",[H][C@@]12CN(C[C@]1([H])[C@H]2N)C1=NC2=C(C=C1F)C(=O)C(=CN2C1=C(F)C=C(F)C=C1)C(O)=O,"Trovafloxacin is a fluoronaphthyridone related to the fluoroquinolones with in vitro activity against a wide range of gram-negative and gram-positive aerobic and anaerobic microorganisms. The bactericidal action of trovafloxacin results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB04953,Ezogabine,Ezogabineis an antiepileptic agent used as an adjuvant treatment of partial-onset seizures.,"['O43526', 'O43525', 'P56696', 'Q9NR82']","As compared to other antiepileptic agents, ezogabine is unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects. The antiepileptics, as a drug class, are routinely used in the treatment of a number of disease states in addition to epilepsy. Ezogabine is highly efficacious in a broad-spectrum of in vivo epilepsy and seizure models. A comparison of antiepileptic form activity of ezogabine with that of conventional anticonvulsants in in vitro models suggests that retigabine is especially likely to be useful in the treatment of pharmacoresistant epilepsy. Retigabine clearly attenuates pain-like behaviors in various animal models of neuropathic pain; it may also prove to be useful in treatment of clinical anxiety disorders. Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.",CCOC(=O)NC1=C(N)C=C(NCC2=CC=C(F)C=C2)C=C1,"Ezogabine has a novel mechanism of action that involves opening of neuronal Kv.-. (formerly KCNQ-) voltage activated potassium channels. These channels (primarily Kv./.) enable generation of the M-current, a sub-threshold potassium current that serves to stabilize the membrane potential and control neuronal excitability. In addition to acting on potassium ion channels, retigabine also affects GABA neurotransmission in the GABA-A receptor, which is a key inhibitory receptor in the central nervous system and is implicated in epilepsy. Malfunctioning of the GABA-A receptor leads to hyperexcitability in the brain, which causes seizures, making this receptor an important target for antiepileptic therapeutics. Apart from increasing the concentration of GABA in the brain (by either enhancing GABA synthesis or blocking GABA metabolism), retigabine allosterically potentiates GABA-induced current in rat cortical neurons in a concentration-dependent manner. Numerous studies have demonstrated that retigabine is effective in a broad spectrum of in vivo epilepsy and seizure models.TargetActionsOrganismUPotassium voltage-gated channel subfamily KQT member Not AvailableHumansUPotassium voltage-gated channel subfamily KQT member Not AvailableHumansUPotassium voltage-gated channel subfamily KQT member Not AvailableHumansUPotassium voltage-gated channel subfamily KQT member Not AvailableHumans",[],"['Acids, Acyclic', 'Amines', 'Aniline Compounds', 'Anticonvulsants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Diamines', 'Drugs that are Mainly Renally Excreted', 'Membrane Transport Modulators', 'Nervous System', 'Polyamines', 'Potassium Channel Opener', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'UGT1A1 Substrates', 'UGT1A3 substrates', 'UGT1A4 substrates', 'UGT1A9 Substrates']" +DB00485,Dicloxacillin,Dicloxacillinis a penicillin used to treat penicillinase-producing bacterial infections that are susceptible to the drug.,"['A0A0E1R3H3', 'Q7CRA4', 'Q8DNB6', 'Q75Y35', 'Q8DR59', 'P0A3M6']","Dicloxacillin is a beta-lactamase resistant penicillin similar to oxacillin. Dicloxacillin hasin vitroactivity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of dicloxacillin results from the inhibition of cell wall synthesis and is mediated through dicloxacillin binding to penicillin binding proteins (PBPs). Dicloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl)C(O)=O,"Dicloxacillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, dicloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that dicloxacillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein inhibitorListeria monocytogenes serotype b str. LLAPenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'Beta-Lactamase Resistant Penicillins', 'beta-Lactams', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Sulfur Compounds']" +DB13179,Troleandomycin,A macrolide antibiotic that is similar to erythromycin.,"['P49228', 'P60723', 'O75469']","Troleandomycin, like other macrolide antibiotics, inhibits bacterial protein synthesis to prevent growth.",CO[C@H]1C[C@H](O[C@H]2[C@H](C)[C@@H](O[C@@H]3O[C@H](C)C[C@@H]([C@H]3OC(C)=O)N(C)C)[C@@H](C)C[C@@]3(CO3)C(=O)[C@H](C)[C@@H](OC(C)=O)[C@@H](C)[C@@H](C)OC(=O)[C@@H]2C)O[C@@H](C)[C@@H]1OC(C)=O,"As a macrolide, troleandomycin binds to the S subunit of the bacterial ribosome. This binding inhibits translocation of tRNA along the A, P, and E sites of the ribosome. With tRNA unable to move from site to site, amino acids cannot be deposited onto the polypeptide chain leading to failure of protein synthesis. Bacterial cell growth and duplication is inhibited without the ability to generate the necessary proteins.TargetActionsOrganismAS ribosomal protein LinhibitorDeinococcus radiodurans (strain ATCC / DSM / JCM / LMG / NBRC / NCIMB / R / VKM B-)AS ribosomal protein LinhibitorEscherichia coli (strain K)UNuclear receptor subfamily group I member activatorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Lactones', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'P-glycoprotein inhibitors']" +DB01044,Gatifloxacin,Gatifloxacinis a fourth generation fluoroquinolone used to treat a wide variety of infections in the body.,"['P72524', 'P0A4L9', 'P72525', 'Q59961']","Gatifloxacin is a synthetic broad-spectrum 8-methoxyfluoroquinolone antibacterial agent for oral or intravenous administration. is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Gatifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.",COC1=C2N(C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1)C1CC1,"The bactericidal action of Gatifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.TargetActionsOrganismADNA gyrase subunit AinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)ADNA gyrase subunit BinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)ADNA topoisomerase subunit AinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)ADNA topoisomerase subunit BinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Compounds used in a research, industrial, or household setting', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Hypoglycemia-Associated Agents', 'Ophthalmic Solutions', 'Ophthalmologicals', 'Pharmaceutical Preparations', 'Pharmaceutical Solutions', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Sensory Organs', 'Solutions', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00222,Glimepiride,Glimepirideis a sulfonylurea drug used to treat type 2 diabetes mellitus.,"['Q14654', 'P48048', 'Q09428']","Glimepiride stimulates the secretion of insulin granules from the pancreatic beta cells and improves the sensitivity of peripheral tissues to insulin to increase peripheral glucose uptake, thus reducing plasma blood glucose levels and glycated hemoglobin (HbA1C) levels. A multi-center, randomized, placebo-controlled clinical trial evaluated the efficacy of glimepiride (1–8 mg) as monotherapy titrated over 10 weeks compared with placebo in T2DM subjects who were not controlled by diet alone.1In this study, there was a reduction in fasting plasma glucose (FPG) by 46 mg/dL, post-prandial glucose (PPG) by 72 mg/dL, and HbA1c by 1.4% more than the placebo.1In another randomized study comprising of patients with T2DM receiving either placebo or one of the three doses (1, 4, or 8 mg) of glimepiride during a 14-week study period, all glimepiride regimens significantly reduced FPG, PPG, and HbA1c values (P < 0.001) compared to placebo by the end of the study period.1The 4- and 8-mg doses of glimepiride were more effective than the 1-mg dose; however, the 4-mg dose provided a nearly maximal antihyperglycemic effect.1",CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)N[C@H]2CC[C@H](C)CC2)C1=O,"ATP-sensitive potassium channels on pancreatic beta cells that are gated by intracellular ATP and ADP. The hetero-octomeric complex of the channel is composed of four pore-forming Kir. subunits and four regulatory sulfonylurea receptor (SUR) subunits. Alternative splicing allows the formation of channels composed of varying subunit isoforms expressed at different concentrations in different tissues.In pancreatic beta cells, ATP-sensitive potassium channels play a role as essential metabolic sensors and regulators that couple membrane excitability with glucose-stimulated insulin secretion (GSIS).When there is a decrease in the ATP:ADP ratio, the channels are activated and open, leading to K+ efflux from the cell, membrane hyperpolarization, and suppression of insulin secretion.In contrast, increased uptake of glucose into the cell leads to elevated intracellular ATP:ADP ratio, leading to the closure of channels and membrane depolarization. Depolarization leads to activation and opening of the voltage-dependent Ca+ channels and consequently an influx of calcium ions into the cell.Elevated intracellular calcium levels causes the contraction of the filaments of actomyosin responsible for the exocytosis of insulin granules stored in vesicles.Glimepiride blocks the ATP-sensitive potassium channel by binding non-specifically to the B sites of both sulfonylurea receptor- (SUR) and sulfonylurea receptor-A (SURA) subunits as well as the A site of SUR subunit of the channel to promote insulin secretion from the beta cell.TargetActionsOrganismAATP-sensitive inward rectifier potassium channel inhibitorHumansAATP-sensitive inward rectifier potassium channel inhibitorHumansAATP-binding cassette sub-family C member inducerHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Substrates', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Hypoglycemia-Associated Agents', 'Immunosuppressive Agents', 'Insulin Secretagogues', 'Oral Hypoglycemics', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB00414,Acetohexamide,A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. Acetohexamide has been discontinued in the US market.,['P48048'],"Acetohexamide is an intermediate-acting, first-generation oral sulfonylurea. It lowers blood sugar by stimulating the pancreatic beta cells to secrete insulin and by helping the body use insulin efficiently. Due to its primary action on the pancreatic beta cells, the drug is only effective when there are functional pancreatic beta cells that can produce insulin granules. Acetohexamide has one-third the potency of chlorpropamide, and twice the potency of tolbutamide; however, similar hypoglycemic efficacy occurs with equipotent dosage of sulfonylureas.",CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1,"Sulfonylureas such as acetohexamide bind to an ATP-dependent K+channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca+channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.TargetActionsOrganismAATP-sensitive inward rectifier potassium channel inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Insulin Secretagogues', 'Oral Hypoglycemics', 'Sulfonamides', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB04878,Voglibose,Vogliboseis an alpha-glucosidase inhibitor indicated in the management of postprandial blood glucose in patients with type II diabetes.,['O43451'],"Voglibose, an alpha-glucosidase inhibitor, is a synthetic compound with potent and enduring therapeutic efficacies against disorders of sensory, motor and autonomic nerve systems due to diabetes mellitus. The drug was approved in Japan in 1994 for the treatment of diabetes, and it is under further investigation by Takeda for the treatment of impaired glucose tolerance. Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of complex carbohydrates (such as starch). Complex carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of complex carbohydrates on blood sugar.",OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O,"Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin-Ac level. (From Drug Therapy in Nursing, nd ed)TargetActionsOrganismAMaltase-glucoamylase, intestinalinhibitorHumans",['Glycemic Control'],"['Alcohols', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Carbohydrates', 'Cyclohexanes', 'Cycloparaffins', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Fatty Alcohols', 'Glycoside Hydrolase Inhibitors', 'Hexanols', 'Lipids', 'Oral Hypoglycemics', 'Sugar Alcohols']" +DB01430,Almitrine,Almitrine is a respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. It is used in the treatment of chronic obstructive pulmonary disease. It is also reported to have a potentially beneficial effect in treating the noctural oxygen desaturation without impairing the quality of sleep.,['P05023'],Almitrine is a respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies.,FC1=CC=C(C=C1)C(N1CCN(CC1)C1=NC(NCC=C)=NC(NCC=C)=N1)C1=CC=C(F)C=C1,Almitrine is an agonist at the peripheral chemoreceptors expressed on carotid bodies. It enhances respiration in patients with chronic obstructive pulmonary disease by increasing the arterial oxygen tension while decreasing the arterial carbon dioxide tension.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-binderHumans,[],"['Alkaloids', 'Central Nervous System Agents', 'Compounds used in a research, industrial, or household setting', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Neuroprotective Agents', 'Pharmaceutical Preparations', 'Piperazines', 'Protective Agents', 'Respiratory System Agents', 'Secologanin Tryptamine Alkaloids', 'Triazines']" +DB00559,Bosentan,Bosentanis a dual endothelin receptor antagonist used to treat pulmonary arterial hypertension.,"['P24530', 'P25101']","Bosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.",COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1,"Endothelin- (ET-) is a neurohormone, the effects of which are mediated by binding to ETAand ETBreceptors in the endothelium and vascular smooth muscle. It displays a slightly higher affinity towards ETAreceptors than ETBreceptors. ET- concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET- in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ETAand ETB.TargetActionsOrganismAEndothelin B receptorantagonistHumansAEndothelin- receptorantagonistHumans",[],"['Amides', 'Antihypertensive Agents', 'Antihypertensives for Pulmonary Arterial Hypertension', 'Benzene Derivatives', 'Benzenesulfonamides', 'BSEP/ABCB11 Inhibitors', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (moderate)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Endothelin Receptor Antagonists', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hepatotoxic Agents', 'OATP1B1/SLCO1B1 Substrates', 'Pyrimidines', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Vasodilating Agents']" +DB00972,Azelastine,Azelastineis a histamine H1-receptor antagonist used intranasally to treat allergic and vasomotor rhinitis and in an ophthalmic solution to treat allergic conjunctivitis.,"['P35367', 'P25021', 'P04054', 'Q16873']","Azelastine antagonizes the actions of histamine, resulting in the relief of histamine-mediated allergy symptoms.2,10,11Onset of action occurs within 15 minutes with intranasal formulations and as quickly as 3 minutes with ophthalmic solutions.1Intranasal formulations have a relatively long-duration of action, with peak effects observed 4-6 hours after the initial dose and efficacy maintained over the entirety of the standard 12 hour dosing interval.2",CN1CCCC(CC1)N1N=C(CC2=CC=C(Cl)C=C2)C2=CC=CC=C2C1=O,"Azelastine is primarily a selective antagonist of histamine H-receptors, with a lesser affinity for H-receptors, used for the symptomatic treatment of allergies.,,,Histamine H-receptors are G-protein-coupled receptors with transmembrane spanning domainsthat are found on nerve endings, smooth muscle cells, and glandular cells.Following allergen exposure in sensitized individuals, IgE-receptor cross-linking on mast cells results in the release of histamine, which binds to H-receptors and contributes to typical allergic symptoms such as itching, sneezing, and congestion.Though its primary mode of action is thought to be via H-receptor antagonism, azelastine (like other second-generation antihistamines) appears to affect other mediators of allergic symptomatology. Azelastine has mast cell-stabilizing properties that prevent the release of interleukin-, tryptase, histamine, and TNF-alphafrom mast cells, and has been shown to reduce mediators of mast cell degranulation such as leukotrienes in the nasal lavage of patients with rhinitis,as well as inhibiting their production and release from eosinophils (potentially via inhibition of phospholipase Aand leukotriene Csynthase).,Additionally, patients using oral azelastine were observed to have significantly reduced concentrations of substance P and bradykinin in nasal secretions, both of which may play a role in nasal itching and sneezing in patients with allergic rhinitis.TargetActionsOrganismAHistamine H receptorantagonistHumansUHistamine H receptorinhibitorHumansUPhospholipase AinhibitorHumansULeukotriene C synthaseinhibitorHumans",[],"['Anti-Allergic Agents', 'Antiallergic Agents, Excl. Corticosteroids', 'Antihistamines for Systemic Use', 'Autonomic Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Inhibitors', 'Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decongestants and Antiallergics', 'Enzyme Inhibitors', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Nasal Preparations', 'Neurotransmitter Agents', 'Ophthalmologicals', 'P-glycoprotein inhibitors', 'Pyridazines', 'Respiratory System Agents', 'Sensory Organs']" +DB00426,Famciclovir,"Famcicloviris a nucleoside analog DNA polymerase inhibitor used for the treatment of recurrent cold sores and genital herpes in healthy patients and patients with HIV, and to manage herpes zoster.",['P04293'],"Famciclovir is a prodrug that undergoes rapid biotransformation to the active antiviral compound penciclovir. Penciclovir is an anti-viral drug which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). Therefore, herpes viral DNA synthesis and replication are selectively inhibited.",CC(=O)OCC(CCN1C=NC2=CN=C(N)N=C12)COC(C)=O,"Famciclovir undergoes rapid biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against herpes simplex virus types (HSV-) and (HSV-) and varicella zoster virus (VZV). In cells infected with HSV-, HSV- or VZV, viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. In vitro studies demonstrate that penciclovir triphosphate inhibits HSV- DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor', 'Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acid Synthesis Inhibitors', 'Nucleosides and Nucleotides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'Ophthalmologicals', 'Purines', 'Sensory Organs']" +DB00711,Diethylcarbamazine,Diethylcarbamazineis an anthelmintic used to treat filarial infections like Wuchereria bancrofti and Loa loa.,"['P09917', 'P23219']",Diethylcarbamazine is an anthelmintic drug that does not resemble other antiparasitic compounds. It is a synthetic organic compound which is highly specific for several parasites and does not contain any toxic metallic elements.,CCN(CC)C(=O)N1CCN(C)CC1,"The mechanism of action of diethylcarbamazine is thought to involve sensitizing the microfilariae to phagocytosis. One study showed that diethylcarbamazine's activity againstBrugia malayimicrofilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway. It confirmed the important role of the arachidonic acid metabolic pathway in diethylcarbamazine's mechanism of actionin vivoand showes that in addition to its effects on the -lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-.TargetActionsOrganismAArachidonate -lipoxygenaseinhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Acyclic', 'Anthelmintics', 'Anti-Infective Agents', 'Antihelminthic', 'Antinematodal Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Carbamates', 'Cholinesterase Inhibitors', 'Enzyme Inhibitors', 'Filaricides', 'Lipoxygenase Inhibitors', 'Piperazine and Derivatives', 'Piperazines']" +DB03796,Palmitic Acid,Palmitic Acidis a fatty used as a food additive and emollient or surfactant in cosmetics.,"['P00709', 'Q07869', 'P08100', 'P50897', 'P02689', 'P09466', 'Q14541', 'P83812', 'P10632', 'O43617', 'Q9X1H9']","Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation",CCCCCCCCCCCCCCCC(O)=O,TargetActionsOrganismUAlpha-lactalbuminNot AvailableHumansUPeroxisome proliferator-activated receptor alphaNot AvailableHumansURhodopsinNot AvailableHumansUPalmitoyl-protein thioesterase Not AvailableHumansUMyelin P proteinNot AvailableHumansUGlycodelinNot AvailableHumansUHepatocyte nuclear factor -gammaNot AvailableHumansULipid binding proteinNot AvailableGeobacillus stearothermophilusUCytochrome P CNot AvailableHumansUTrafficking protein particle complex subunit Not AvailableHumansUFatty acid-binding protein TM_Not AvailableThermotoga maritima (strain ATCC / MSB / DSM / JCM ),[],"['Enzyme Inhibitors', 'Fatty Acids', 'Lipids', 'Palmitic Acids']" +DB04876,Vildagliptin,Vildagliptinis a once-daily dipeptidyl peptidase 4 (DPP-4) inhibitor used in the management of type 2 diabetes mellitus.,['P27487'],"Vildagliptin works to improve glycemic control in type II diabetes mellitus by enhancing the glucose sensitivity of beta-cells (β-cells) in pancreatic islets and promoting glucose-dependent insulin secretion. Increased GLP-1 levels leads to enhanced sensitivity of alpha cells to glucose, promoting glucagon secretion. Vildagliptin causes an increase in the insulin to glucagon ratio by increasing incretin hormone levels: this results in a decrease in fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. It also has no effects on insulin secretion or blood glucose levels in individuals with normal glycemic control.6In clinical trials, treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta-cells, proinsulin to insulin ratio, and measures of beta-cell responsiveness from the frequently-sampled meal tolerance test.6Vildagliptin has improves glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels.2",OC12CC3CC(C1)CC(C3)(C2)NCC(=O)N1CCC[C@H]1C#N,"Glucagon-like peptide- (GLP-) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones that regulate blood glucose levels and maintain glucose homeostasis. It is estimated that the activity of GLP- and GIP contribute more than % to the insulin response to an oral glucose challenge. They stimulate insulin secretion in a glucose-dependent manner via G-protein-coupled GIP and GLP- receptor signalling. In addition to their effects on insulin secretion, GLP- is also involved in promoting islet neogenesis and differentiation, as well as attenuating pancreatic beta-cell apoptosis. Incretin hormones also exert extra-pancreatic effects, such as lipogenesis and myocardial function.In type II diabetes mellitus, GLP- secretion is impaired, and the insulinotropic effect of GIP is significantly diminished.Vildagliptin exerts its blood glucose-lowering effects by selectively inhibiting dipeptidyl peptidase- (DPP-), an enzyme that rapidly truncates and inactivates GLP- and GIP upon their release from the intestinal cells. DPP- cleaves oligopeptides after the second amino acid from the N-terminal end. Inhibition of DPP- substantially prolongs the half-life of GLP- and GIP, increasing the levels of active circulating incretin hormones.The duration of DPP- inhibition by vildagliptin is dose-dependent.Vildagliptin reduces fasting and prandial glucose and HbAc. It enhances the glucose sensitivity of alpha- and beta-cells and augments glucose-dependent insulin secretion. Fasting and postprandial glucose levels are decreased, and postprandial lipid and lipoprotein metabolism are also improved.,TargetActionsOrganismADipeptidyl peptidase inhibitorHumans",[],"['Agents causing angioedema', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Bridged-Ring Compounds', 'Cycloparaffins', 'DPP-IV Inhibitors', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Glucagon-Like Peptide 1', 'Nitriles', 'Oral Hypoglycemics', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Pyrrolidines']" +DB06292,Dapagliflozin,Dapagliflozinis a sodium-glucose cotransporter 2 inhibitor used in the management of type 2 diabetes mellitus.,['P31639'],"Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback.10Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients with type 2 diabetes mellitus following the administration of dapagliflozin. Dapagliflozin doses of 5 or 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day at Week 12. A near-maximum glucose excretion was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin also results in increases in urinary volume. After discontinuation of dapagliflozin, on average, the elevation in urinary glucose excretion approaches baseline by about 3 days for the 10 mg dose.10Dapagliflozin was not associated with clinically meaningful prolongation of QTc interval at daily doses up to 150 mg (15 times the recommended maximum dose) in a study of healthy subjects. In addition, no clinically meaningful effect on QTc interval was observed following single doses of up to 500 mg (50 times the recommended maximum dose) of dapagliflozin in healthy subjects.10",CCOC1=CC=C(CC2=C(Cl)C=CC(=C2)[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C1,Dapagliflozin inhibits the sodium-glucose cotransporter (SGLT) which is primarily located in the proximal tubule of the nephron.SGLT facilitates % of glucose reabsorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine.This excretion allows for better glycemic control and potentially weight loss in patients with type diabetes mellitus.TargetActionsOrganismASodium/glucose cotransporter antagonistinhibitorHumans,[],"['Alimentary Tract and Metabolism', 'Benzene Derivatives', 'Blood Glucose Lowering Agents', 'Carbohydrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diuretics', 'Drugs Used in Diabetes', 'Glycosides', 'Hypotensive Agents', 'Oral Hypoglycemics', 'P-glycoprotein substrates', 'Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors', 'Sodium-Glucose Transport Proteins, antagonists & inhibitors', 'Sodium-Glucose Transporter 2 Inhibitors', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB11642,Pitolisant,Pitolisantis an antagonist and inverse agonist at the histamine H3 receptor that is used to treat narcolepsy in adults.,"['Q9Y5N1', 'Q12809']","Pitolisant promotes wakefulness in narcolepsy by enhancing histaminergic signalling in the central nervous system. It does not significantly bind to H1, H2, or H4 receptors.10In patients with narcolepsy in presence or absence of cataplexy, treatment of pitolisant was associated with an improvement in the level and duration of wakefulness and daytime alertness assessed by objective measures of ability to sustain wakefulness (e.g. Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) Scores) and attention (e.g. Sustained Attention to Response Task (SART)).8Pitolisant also improved the frequency and severity of narcolepsy-associated cataplexy.1Pitolisant acts as a blocker at hERG channels. In two QT studies, supra-therapeutic doses of pitolisant (3-6-times the therapeutic dose, that is 108 mg to 216 mg) produced mild to moderate prolongation of QTc interval (10-13 ms).8",ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1,"Signalling of histaminergic neurons plays a key role in activating the arousal system with widespread projections to the whole brainvia activating orexin receptors.Narcolepsy is characterized by insufficient neurotransmission by orexins, or hypocretins, which are excitatory peptides released by neurons located from the lateral hypothalamus. These neurons project to aminergic neurons, such as histaminergic or noradrenergic neurons, that are responsible for the effects of orexin and control of wakefulness.Histamine H receptors are presynaptic inhibitory autoreceptorsthat are located in the cerebral cortex, hypothalamus, hippocampus, and basal ganglia.H receptors promote the re-uptake of histamine at synaptic terminals and attenuate further histamine release into the synapse.By blocking H autoreceptors and increasing the levels of histamine transmitters at the synapse, pitolisant enhances the activity of histaminergic neurons and promotes wakefulness.Inverse agonism of pitolisant at H receptors also leads to enhanced synthesis and release of endogenous histamine over the basal level.Pitolisant acts as a high-affinity competitive antagonist (Ki . nM) and as an inverse agonist (EC . nM) at the human H receptorand mediates its pharmacological action at the presynaptic level.It is thought to bind to the antagonist binding site of the H receptor, which is located within the transmembrane core just below the extracellular loops. Piperidines form a salt bridge with Glu in the membrane-spanning segment, and the hydroxyl of Tyr is H-bonded with the central oxygen of piperidine.Pitolisant displays high selectivity for H receptors compared to other histamine receptor subtypes. Pitolisant also modulates acetylcholine, noradrenaline and dopamine release in the brain by increasing the levels of neurotransmitters but does not increase dopamine release in the stratal complex, including the nucleus accumbens.At lower nanomolar concentrations, pitolisant acts as an inverse agonist at H receptors and enhances the release of endogenous histamine over the basal level.TargetActionsOrganismAHistamine H receptorantagonistinverse agonistHumansNPotassium voltage-gated channel subfamily H member blockerHumans",[],"['Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Histamine Antagonists', 'Histamine H3 Antagonists', 'Histamine-3 (H3) Receptor Antagonists/Inverse Agonists', 'Histamine-3 Receptor Antagonist/Inverse Agonist', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'OCT1 inhibitors', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Receptors, Histamine H3']" +DB08860,Pitavastatin,Pitavastatinis an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke.,"['P04035', 'P20701']","Pitavastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.4,5Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.4Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.8,9,10,11,12Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.4,5Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.15,14Skeletal Muscle EffectsPitavastatin may cause myopathy (muscle pain, tenderness, or weakness with creatine kinase (CK) above ten times the upper limit of normal) and rhabdomyolysis (with or without acute renal failure secondary to myoglobinuria). Rare fatalities have occurred as a result of rhabdomyolysis with statin use, including pitavastatin. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. As dosages of pitavastatin greater than 4mg per day were associated with an increased risk of severe myopathy, the product monograph recommends a maximum daily dose of 4mg once daily.32The risk of myopathy during treatment with pitavstatin may be increased with concurrent administration of interacting drugs such asfenofibrate,niacin,gemfibrozil, andcyclosporine. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered withcolchicine, and caution should therefore be exercised when prescribing these two medications together.32Real-world data from observational studies has suggested that 10-15% of people taking statins may experience muscle aches at some point during treatment.28Hepatic DysfunctionIncreases in serum transaminases have been reported with pitavastatin. In most cases, the elevations were transient and either resolved or improved on continued therapy or after a brief interruption in therapy. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin.32Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury.32Increases in HbA1c and Fasting Serum Glucose LevelsIncreases in HbA1c and fasting serum glucose levels have been reported with statins, including pitavastatin. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.32An in vitro study found thatatorvastatin,pravastatin,rosuvastatin, andpitavastatinexhibited a dose-dependent cytotoxic effect on human pancreas islet β cells, with reductions in cell viability of 32, 41, 34 and 29%, respectively, versus control. Moreover, insulin secretion rates were decreased by 34, 30, 27 and 19%, respectively, relative to control.24",O[C@H](C[C@H](O)\C=C\C1=C(N=C2C=CC=CC2=C1C1=CC=C(F)C=C1)C1CC1)CC(O)=O,"Pitavastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (-hydroxy--methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis.Pitavastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increase hepatic uptake of LDL, thereby reducing circulating LDL-C levels.In vitro and in vivo animal studies also demonstrate that statins exert vasculoprotective effects independent of their lipid-lowering properties, also known as the pleiotropic effects of statins.This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.Statins have also been found to bind allosterically to β integrin function-associated antigen- (LFA-), which plays an important role in leukocyte trafficking and in T cell activation.TargetActionsOrganismA-hydroxy--methylglutaryl-coenzyme A reductaseinhibitorHumansUIntegrin alpha-LNot AvailableHumans",[],"['Agents Causing Muscle Toxicity', 'Anticholesteremic Agents', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Hypolipidemic Agents', 'Hypolipidemic Agents Indicated for Hyperlipidemia', 'Lipid Modifying Agents', 'Lipid Modifying Agents, Plain', 'Lipid Regulating Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'OATP2B1/SLCO2B1 substrates', 'P-glycoprotein substrates', 'Toxic Actions', 'UGT1A3 substrates', 'UGT2B7 substrates']" +DB01014,Balsalazide,Balsalazideis an aminosalicylate used to treat ulcerative colitis.,"['P37231', 'P35354', 'P23219', 'P09917']","Balsalazide is a prodrug that has little or no pharmacologic activity until it is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid), an anti inflammatory drug indicated for the treatment of mildly to moderately active ulcerative colitis. Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the intert 4-aminobenzoyl-(beta)-alanine. As a result, the spectrum of pharmacologic activity of balsalazide is similar to that of mesalamine.",OC(=O)CCNC(=O)C1=CC=C(C=C1)\N=N\C1=CC=C(O)C(=C1)C(O)=O,"The mechanism of action of -aminosalicylic acid is unknown, but appears exert its anti-inflammatory effects locally (in the GI tract) rather than systemically. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways (catalyzes the formation of prostaglandin precursors from arachidonic acid), and through the lipoxygenase pathways (catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid and its metabolites), is increased in patients with chronic inflammatory bowel disease. Therefore, it is possible that -aminosalicylic acid diminishes inflammation by blocking production of arachidonic acid metabolites in the colon through both the inhibition of cyclooxygenase and lipoxygenase.TargetActionsOrganismAPeroxisome proliferator-activated receptor gammaagonistHumansAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansAArachidonate -lipoxygenaseinhibitorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Alimentary Tract and Metabolism', 'Aminobenzoates', 'Aminosalicylate', 'Aminosalicylic Acids', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Benzene Derivatives', 'Benzoates', 'Colitis, Ulcerative', 'Gastrointestinal Agents', 'Hydrazines', 'Hydroxy Acids', 'Hydroxybenzoates', 'Inflammatory Bowel Diseases', 'Intestinal Antiinflammatory Agents', 'meta-Aminobenzoates', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Phenols', 'Prodrugs', 'Salicylates', 'Sensory System Agents']" +DB09221,Polaprezinc,"Polaprezinc is a chelated form of zinc and L-carnosine. It is a zinc-related medicine approved for the first time in Japan, which has been clinically used to treat gastric ulcers5,6. It was determined that polaprezinc may be effective in pressure ulcer treatment3. A study in 2013 showed that CO-administration of polaprezinc may be effective against small intestine mucosal injury associated with long-term aspirin therapy1.","['P01375', 'P05231', 'P08700', 'P17948', 'P01138', 'P09619', 'P07900', 'P08238']",Used to treat/manage peptic ulcer disease or irritation of the gastrointestinal tract by promoting tissue healing by the elimination of free radicals1.,NCCC(=O)N1[Zn]OC(=O)[C@@H]1CC1=CN=CN1,"Polaprezinc increases the expression of various antioxidant enzymes, including superoxide dismutase (SOD-), SOD-, heme oxygenase- (HO-), glutathione S-transferase (GST), glutathione peroxidase (GSH-px), peroxidredoxin- (PRDX; PRXI) and PRXD (PRXV).This process occurs in the gastric mucosa, defending mucosal cells against reactive oxygen species. This drug inhibits the activity of the transcription factor nuclear factor-kappaB (NF-kB) and decreases the expression of various inflammatory cytokines, including interleukin (IL) beta, IL-, IL-, and tumor necrosis factor alpha (TNF-a).Polaprezinc also promotes the expression of numerous growth factors, including as platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), in addition to various heat shock proteins (HSPs), including HSP, HSP, HSP, HSP, HSP, and HSP. This process promotes tissue growth and protects against damage the gastric mucosa.TargetActionsOrganismUTumor necrosis factorinhibitorHumansUInterleukin-inhibitorHumansUInterleukin-inhibitorHumansUVascular endothelial growth factor receptor agonistHumansUBeta-nerve growth factoragonistHumansUPlatelet-derived growth factor receptor betaagonistHumansUHeat shock protein HSP -alphaagonistHumansUHeat shock protein HSP -betaagonistHumans",[],"['Amino Acids, Peptides, and Proteins', 'Anti-Ulcer Agents', 'Dipeptides', 'Gastrointestinal Agents', 'Metal cations', 'Metal divalent cations', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptides', 'Proteins', 'Tumor Necrosis Factor Blockers', 'Zinc Compounds']" +DB02300,Calcipotriol,Calcipotriolis a topical synthetic vitamin D2 derivative used in the treatment of plaque psoriasis.,['P11473'],"Calcipotriene is a synthetic analog of vitamin D. In humans, the natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol) in the skin.",O[C@H](\C=C\[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C)C1CC1,"The precise mechanism of calcipotriol in remitting psoriasis is not well-understood, however, it has been shown to have comparable affinity with calcitriol for the Vitamin D receptor while being less than % the activity in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis and are believed to undergo modulation of gene expression with binding of calcipotriol to the VDR. This modulation is thought to affect gene products related to cell differentiation and proliferation.TargetActionsOrganismUVitamin D receptorantagonistHumans",[],"['Antipsoriatics', 'Antipsoriatics for Topical Use', 'Cholestanes', 'Cholestenes', 'Dermatologicals', 'Fused-Ring Compounds', 'Lipids', 'Membrane Lipids', 'Misc. Skin and Mucous Membrane Agents', 'Secosteroids', 'Steroids', 'Sterols', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00836,Loperamide,"Loperamideis a long acting antidiarrheal used to control nonspecific diarrhea and chronic diarrhea caused by inflammatory bowel disease, or gastroenteritis.","['P35372', 'P41143', 'P41145', 'P0DP23', 'P01189', 'O00555', 'Q12809']","Loperamide is an anti-diarrheal agent that provides symptomatic relief of diarrhea.8It decreases peristalsis and fluid secretion in the gastrointestinal tract, delays colonic transit time, and increases the absorption of fluids and electrolytes from the gastrointestinal tract.2,1,5Loperamide also increases rectal tone,1reduces daily fecal volume, and increases the viscosity and bulk density of feces.8It also increases the tone of the anal sphincter, thereby reducing incontinence and urgency.3,8The onset of action is about one hour and the duration of action can be up to three days.3While loperamide is a potent mu-opioid receptor agonist,3it does not mediate significant analgesic activity at therapeutic and supratherapeutic doses.2,3However, at high doses of loperamide, inhibition of P-glycoprotein-mediated drug efflux may allow loperamide to cross the blood-brain barrier, where loperamide can exert central opioid effects and toxicity.1At very high plasma concentrations, loperamide can interfere with cardiac conduction.4Because loperamide inhibits the Na+-gated cardiac channels1and ether-a-go-go–related gene potassium channels,4the drug can prolong the QRS complex and the QTc interval, which can lead to ventricular dysrhythmias, monomorphic and polymorphic ventricular tachycardia, torsade de pointes, ventricular fibrillation, Brugada syndrome, cardiac arrest, and death.1",CN(C)C(=O)C(CCN1CCC(O)(CC1)C1=CC=C(Cl)C=C1)(C1=CC=CC=C1)C1=CC=CC=C1,"Enteric neurons synthesize and release endogenous opioid peptides and other neurotransmitters, such as acetylcholine and substance P. Endogenous opioids bind to opioid receptors expressed on these neurons to regulate gastrointestinal signalling, motility, and balance of fluids and electrolytes.Loperamide acts on the mu-opioid receptor expressed on the circular and longitudinal intestinal muscle.Receptor binding leads to the recruitment of G-protein receptor kinases and the activation of downstream molecular cascades that inhibit enteric nerve activity.By inhibiting the excitability of enteric neurons, loperamide suppresses neurotransmitter release, pre-synaptic and post-synaptic inhibition of transmission of excitatory and inhibitory motor pathways, and secretomotor pathways.Loperamide inhibits the release of acetylcholine and prostaglandins,thereby reducing propulsive peristalsis and increasing intestinal transit time.,Loperamide stimulates the intestinal absorption of water and electrolytes by inhibiting calmodulin.Loperamide can bind to and hyperpolarize submucosal secretomotor neurons, promoting dry, hard stools.TargetActionsOrganismAMu-type opioid receptoragonistHumansUDelta-type opioid receptoragonistHumansUKappa-type opioid receptoragonistHumansUCalmodulininhibitorHumansUPro-opiomelanocortinmodulatorHumansNVoltage-dependent P/Q-type calcium channel subunit alpha-AblockerHumansNPotassium voltage-gated channel subfamily H member blockerHumans",[],"['Agents causing hyperkalemia', 'Alimentary Tract and Metabolism', 'Antiarrhythmic agents', 'Antidiarrheals', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antipropulsives', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Gastrointestinal Agents', 'Moderate Risk QTc-Prolonging Agents', 'Opioid Agonist', 'P-glycoprotein substrates', 'Piperidines', 'QTc Prolonging Agents']" +DB00505,Tridihexethyl,"Tridihexethyl is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Tridihexethyl is an antimuscarinic, anticholinergic drug. Tridihexethyl is no longer available in the US market.","['P20309', 'P11229', 'P08172']","Tridihexethyl is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Tridihexethyl is an antimuscarinic, anticholinergic drug.",CC[N+](CC)(CC)CCC(O)(C1CCCCC1)C1=CC=CC=C1,"Tridihexethyl binds the muscarinic acetylcholine receptor. It may block all three types of muscarinic receptors including M- receptors in the CNS and ganglia, M- receptors in the heart (vagus) and M- receptors at the parasympathetic NEJ system. The muscarinic acetylcholine receptors mediate various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Tridihexethyl inhibits vagally mediated reflexes by antagonizing the action of acetylcholine. This in turn reduces the secretion of gastric acids in the stomach.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Amines', 'Ammonium Compounds', 'Anticholinergic Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Muscarinic Antagonists', 'Nitrogen Compounds', 'Onium Compounds', 'Synthetic Anticholinergics, Quaternary Ammonium Compounds']" +DB04690,Camptothecin,"Camptothecin is an alkaloid isolated from the stem wood of the Chinese tree,Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase, type I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.",['P11387'],Camptothecin demonstrated strong anticancer activity in preliminary clinical trials but also low solubility and adverse drug reaction. Camptothecin is believed to be a potent topoisomerase inhibitor that interferes with the essential function of topoisomerase in DNA replication.,CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O,"Camptothecin binds to the topoisomerase I and DNA complex resulting in a ternary complex, stabilizing it and preventing DNA re-ligation and therefore causes DNA damage which results in apoptosis.TargetActionsOrganismUDNA topoisomerase inhibitorHumans",[],"['Alkaloids', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'BCRP/ABCG2 Substrates', 'Enzyme Inhibitors', 'P-glycoprotein substrates', 'Topoisomerase I Inhibitors', 'Topoisomerase Inhibitors']" +DB00249,Idoxuridine,"Idoxuridineis a pyrimidine analog antiviral used for the treatment of viral eye infections, including herpes simplex keratitis.",['Q9QNF7'],"In chemical structure idoxuridine closely approximates the configuration of thymidine, one of the four building blocks of DNA (the genetic material of the Herpes virus). As a result, idoxuridine is able to replace thymidine in the enzymatic step of viral replication or ""growth"". The consequent production of faulty DNA results in a pseudostructure which cannot infect or destroy tissue. In short, by pre-empting a vital building block in the genetic material of the Herpes simplex virus, Herplex-D topical solution destroys the infective and destructive capacity of the viral material. The virus infected cell may only be attacked during the period of active synthesis of DNA. This occurs early in the development of the Herpes simplex lesion, but at different times in different cells. Therefore, ideally, the affected area should remain saturated with the antiviral agent.",OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(I)C(=O)NC1=O,Idoxuridine acts as an antiviral agent by inhibiting viral replication by substituting itself for thymidine in viral DNA. This in turn inhibits thymidylate phosphorylase and viral DNA polymerases from properly functioning. The effect of Idoxuridine results in the inability of the virus to reproduce or to infect/destroy tissue.TargetActionsOrganismADNAotherHumansUThymidine kinaseunknownHHV-,[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Deoxyribonucleosides', 'Deoxyuridine', 'Dermatologicals', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Analog Antiviral', 'Nucleosides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'Ophthalmologicals', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Sensory Organs']" +DB05246,Methsuximide,Methsuximideis a succinimide anticonvulsant that increases the seizure threshold. Primarily used for childhood absence seizures. Functions by suppressing paroxysmal spike-and-wave patterns associated with lapses of consciousness in absence seizures.,['O43497'],"Used in the treatment of epilepsy. Methsuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.",CN1C(=O)CC(C)(C1=O)C1=CC=CC=C1,"Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-G gives rise to T-type calcium currents. T-type calcium channels belong to the ""low-voltage activated (LVA)"" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.TargetActionsOrganismAVoltage-dependent T-type calcium channel subunit alpha-GinhibitorHumans",[],"['Agents causing hyperkalemia', 'Anti-epileptic Agent', 'Antiarrhythmic agents', 'Anticonvulsants', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Imides', 'Nervous System', 'Potential QTc-Prolonging Agents', 'Pyrrolidines', 'Pyrrolidinones', 'QTc Prolonging Agents', 'Succinimide Derivatives']" +DB00402,Eszopiclone,"Eszopicloneis a sedative-hypnotic used in the treatment of insomnia, improving both the latency phase and the maintenance phase of sleep.","['P14867', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P47869', 'P34903', 'P31644']","Eszopiclone rapidly induces sleep and decreases sleep latency. It also aids in the maintenance of sleep, preventing frequent awakenings.3,4,10This drug has shown anticonvulsant and muscle relaxant properties in animals but is used in humans for its sedating effects.9Eszopiclone is a central nervous system depressant with various effects. These include changes in alertness and motor coordination and the risk of next morning impairment, increasing with the amount of eszopiclone administered. Exercise caution and advise against driving a motor vehicle or activities that require full mental alertness the next morning.10Complex sleep behaviors may result from eszopiclone use. Eszopiclone should be discontinued in these cases.15Avoid the use of alcohol and other CNS depressants when eszopiclone is administered. Advise patients to skip the eszopiclone dose if alcohol has been consumed before bed or during the evening. Use the smallest dose of eszopiclone as possible, especially in elderly patients, who may experience exaggerated drug effects. Though the potential for dependence and abuse with eszopiclone is lower than for other hypnotic drugs, this drug has been abused and is known to cause dependence.14",CN1CCN(CC1)C(=O)O[C@@H]1N(C(=O)C2=NC=CN=C12)C1=NC=C(Cl)C=C1,"The exact mechanism of action of eszopiclone is unknown at this time but is thought to occur via binding with the GABA receptor complexes at binding sites located near benzodiazepine receptors, possibly explaining its hypnotic and sedative effects.,It has particular affinity for GABA-A (or GABAA) receptor subunits , and .,,Eszopiclone increases GABA-A channel currents significantly.GABA-A channels are major inhibitory channels that cause CNS depression when their receptors are activated.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGABA(A) Receptorpositive allosteric modulatorHumansUGamma-aminobutyric acid receptor subunit alpha-agonistHumansUGamma-aminobutyric acid receptor subunit alpha-agonistHumansUGamma-aminobutyric acid receptor subunit alpha-agonistHumans",[],"['Benzodiazepine hypnotics and sedatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Hypnotics (Nonbenzodiazepine)', 'Hypnotics and Sedatives', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Nervous System', 'Photosensitizing Agents', 'Piperazines', 'Psycholeptics', 'Pyrazines', 'Pyridines', 'Zopiclone and prodrugs']" +DB01129,Rabeprazole,"Rabeprazoleis a proton pump inhibitor used to help gastrointestinal ulcers heal, to treat symptoms of gastroesophageal reflux disease (GERD), to eradicate Helicobacter pylori, and to treat hypersecretory conditions such as Zollinger-Ellison Syndrome.",['P20648'],"Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H+, K+-ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.",COCCCOC1=C(C)C(CS(=O)C2=NC3=CC=CC=C3N2)=NC=C1,"Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+/K+ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH . with a half-life of seconds.TargetActionsOrganismAPotassium-transporting ATPase alpha chain inhibitorHumans",[],"['2-Pyridinylmethylsulfinylbenzimidazoles', 'Acetates', 'Acid Reducers', 'Acids, Acyclic', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'BCRP/ABCG2 Inhibitors', 'Benzimidazoles', 'Butylpyrazolidines', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hydroxy Acids', 'Musculo-Skeletal System', 'Proton Pump Inhibitors', 'Proton-pump Inhibitors', 'Pyrazoles', 'Pyrazolones', 'Pyridines', 'Sulfoxides', 'Sulfur Compounds', 'Topical Products for Joint and Muscular Pain']" +DB00905,Bimatoprost,Bimatoprostis a prostaglandin analog used to treat hypotrichosis of the eyelashes and intraocular pressure in open angle glaucoma or ocular hypertension.,"['P43088', 'P34995', 'P43115']","High intraocular pressure is a major risk factor for glaucoma-related visual field loss. A linear relationship exists between intraocular pressure and the risk of damaging the optic nerve, which can lead to considerable visual impairment.13Therefore, conditions such as ocular hypertension and glaucoma can cause dangerous elevations of intraocular pressure. Bimatoprost rapidly decreases intraocular pressure and reduces the risk for visual field loss from ocular hypertension due to various causes.13Other effects of this drug may include gradual changes in eyelid pigmentation, changes in iris pigmentation, changes in eyelash pigmentation, growth and thickness.13Patients should be informed of these possible effects, especially if this drug is only administered to one eye, which may noticeably change in appearance with bimatoprost treatment.13",CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1,"Bimatoprost imitates the effects of prostamides, specifically prostaglandin Fα.Bimatoprost mildly stimulates aqueous humor outflow, relieving elevated intraocular pressure and decreasing the risk of optic nerve damage. It is thought that bimatoprost reduces intraocular pressure (IOP) in humans by causing an increase in outflow of the aqueous humor via the trabecular meshwork and uveoscleral pathways.It achieves the above effects by decreasing tonographic resistance to aqueous humor outflow.Bimatoprost does not affect aqueous humor production.TargetActionsOrganismAProstaglandin F-alpha receptoragonistHumansAProstaglandin E receptor EP subtypeagonistHumansAProstaglandin E receptor EP subtypeagonistHumans",[],"['Amides', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Autacoids', 'Biological Factors', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Inflammation Mediators', 'Lipids', 'Ophthalmologicals', 'Prostaglandin analogs reducing intraocular pressure (IOP)', 'Prostaglandins', 'Prostaglandins F, Synthetic', 'Prostaglandins, Synthetic', 'Sensory Organs']" +DB00969,Alosetron,Alosetronis a 5-HT3 antagonist used to treat diarrhea-predominant IBS.,['P46098'],"Alosetron is a potent and selective antagonist of the serotonin 5-HT3receptor type. Activation of these receptors and the resulting neuronal depolarization affects the regulation of visceral pain, colonic transit, and GI secretions processes that are related to IBS. By blocking these receptors, alosetron is able to effectively control IBS.",CN1C2=C(C3=CC=CC=C13)C(=O)N(CC1=C(C)NC=N1)CC2,"Alosetron is a potent and selective -HTreceptor antagonist. -HTreceptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of irritable bowel syndrome (IBS). -HTreceptor antagonists such as alosetron inhibit activation of non-selective cation channels which results in the modulation of serotonin-sensitive GI motor and sensory processes.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'Antiemetic Serotonin 5-HT3 Receptor Antagonists', 'Antiemetics', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Functional Gastrointestinal Disorders', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Neurotransmitter Agents', 'Pyridines', 'Serotonin 3 Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB01591,Solifenacin,"Solifenacinis a muscarinic antagonist with antispasmodic properties used to treat urge urinary incontinence, urgency, and urinary frequency associated with an overactive bladder.","['P20309', 'P08172', 'P08173', 'P08912', 'P11229']","Solifenacin antagonizes the M2 and M3 muscarinic receptors in the bladder to treat an overactive bladder.3,2It has a long duration of action as it is usually taken once daily.3Patients taking solifenacin should be aware of the risks of angioedema and anaphylaxis.3",O=C(O[C@H]1CN2CCC1CC2)N1CCC2=CC=CC=C2[C@@H]1C1=CC=CC=C1,"Solifenacin is a competitive muscarinic receptor antagonist.It has the highest affinity for M, M, and M muscarinic receptors.% of the muscarinic receptors in the bladder are M, while % are M.Solifenacin's antagonism of the M receptor prevents contraction of the detrusor muscle, while antagonism of the M receptor may prevent contraction of smooth muscle in the bladder.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Agents that produce hypertension', 'Anticholinergic Agents', 'Cholinergic Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Urinary Frequency and Incontinence', 'Drugs Used in Benign Prostatic Hypertrophy', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinuclidines', 'Tetrahydroisoquinolines', 'Urological Agents', 'Urologicals']" +DB00496,Darifenacin,Darifenacinis an M3 muscarinic receptor blocker used to treat urinary incontinence.,"['P20309', 'P11229', 'P08172', 'P08173', 'P08912']","Darifenacin is a competitive muscarinic receptor antagonist.In vitrostudies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9 and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.",NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C1=CC=CC=C1)C1=CC=CC=C1,"Darifenacin selectively antagonizes the muscarinic M receptor. M receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anticholinergic Agents', 'Cholinergic Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Urinary Frequency and Incontinence', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Urological Agents', 'Urologicals']" +DB00849,Methylphenobarbital,"A barbiturate that is metabolized to phenobarbital. It has been used for similar purposes, especially in epilepsy, but there is no evidence mephobarbital offers any advantage over phenobarbital.","['P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P14867', 'P43681', 'P36544', 'P42262', 'Q13002', 'O75469']","Methylphenobarbital, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia.",CCC1(C(=O)NC(=O)N(C)C1=O)C1=CC=CC=C1,"Methylphenobarbital binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumansUNuclear receptor subfamily group I member activatorHumans",[],"['Anticholinergic Agents', 'Anticonvulsants', 'Barbiturates', 'Barbiturates and Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Phenobarbital and similars', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones']" +DB01232,Saquinavir,Saquinaviris an HIV protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 with advanced immunodeficiency.,['Q72874'],"Saquinavir exerts its antiviral activity by inhibiting an enzyme critical for the HIV-1 viral lifecycle.6Like other protease inhibitors, saquinavir has a propensity for participating in drug interactions - use caution when administering saquinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common.6Saquinavir is known to increase the QTc-interval in otherwise healthy individuals, and should therefore be used with caution in patients maintained on other QTc-prolonging medications or for whom prolongation of the QTc-interval may be of particular consequence (e.g. patients with pre-existing heart disease).6Careful and regular monitoring of patient bloodwork is recommended, as saquinavir has been associated with the development of metabolic complications (e.g. diabetes mellitus, hyperlipidemia) and worsening of pre-existing liver disease.6",[H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)C1=NC3=C(C=CC=C3)C=C1)[C@@H](C2)C(=O)NC(C)(C)C,"The HIV lifecycle is comprised of distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious.At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV- protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle.Saquinavir is an inhibitor of the HIV- protease enzyme.Its design is based on the ""peptidomimetic"" principle, wherein the molecule contains a hydroxyethylene scaffold that mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved.By preventing HIV- protease activity, and thus the proteolysis of the Gag polyprotein, saquinavir results in the production of immature, non-infectious viral particles.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Agents Causing Muscle Toxicity', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'BCRP/ABCG2 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors (strong)', 'Cytochrome P-450 CYP3A7 Inhibitors (weak)', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'Isoquinolines', 'Moderate Risk QTc-Prolonging Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OCT1 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protease Inhibitors', 'QTc Prolonging Agents', 'Quinolines', 'Viral Protease Inhibitors']" +DB01291,Pirbuterol,Pirbuterolis a beta-2 adrenergic agonist and bronchodilator used for the symptomatic treatment of asthma.,"['P07550', 'P08588']","Pirbuterol is a beta-2 adrenergic bronchodilator. In vitro studies and in vivo pharmacologic studies have demonstrated that pirbuterol has a preferential effect on beta-2 adrenergic receptors compared with isoproterenol. While it is recognized that beta-2 adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta-2 receptors in the human heart, existing in a concentration between 10-50%. The precise function of these receptors has not been established.",CC(C)(C)NCC(O)C1=NC(CO)=C(O)C=C1,"The pharmacologic effects of beta adrenergic agonist drugs, including pirbuterol, are at least in proof attributable to stimulation through beta adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (AlP) to cyclic-† ,†-adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-Agonists', 'Adrenergics for Systemic Use', 'Adrenergics, Inhalants', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Agents to Treat Airway Disease', 'Alcohols', 'Amines', 'Amino Alcohols', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Drugs for Obstructive Airway Diseases', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Protective Agents', 'Respiratory System Agents', 'Selective Beta 2-adrenergic Agonists']" +DB00006,Bivalirudin,Bivalirudinis a direct thrombin inhibitor used to treat heparin-induced thrombocytopenia and to prevent thrombosis during percutaneous coronary intervention.,['P00734'],Bivalirudin mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.,CC[C@H](C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](N)CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O,"Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.TargetActionsOrganismAProthrombininhibitorHumans",[],"['Amino Acids, Peptides, and Proteins', 'Anticoagulants', 'Antithrombins', 'Blood and Blood Forming Organs', 'Enzyme Inhibitors', 'Hematologic Agents', 'Peptides', 'Protease Inhibitors', 'Serine Protease Inhibitors', 'Thrombin Inhibitors']" +DB00757,Dolasetron,Dolasetronis an antinauseant and antiemetic used in chemotherapy and postoperatively.,['P46098'],"Dolasetron is a highly specific and selective serotonin 5-HT3receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. It is structurally and pharmacologically related to other 5-HT3receptor agonists. The serontonin 5-HT3receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.",[H][C@@]1(C[C@@]2([H])C[C@]3([H])C[C@@]([H])(C1)N2CC3=O)OC(=O)C1=CNC2=C1C=CC=C2,"Dolasetron is a selective serotonin -HTreceptor antagonist. In vivo, the drug is rapidly converted into its major active metabolite, hydrodolasetron, which seems to be largely responsible for the drug's pharmacological activity. The antiemetic activity of the drug is brought about through the inhibition of -HTreceptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of -HTreceptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'Antiemetic Serotonin 5-HT3 Receptor Antagonists', 'Antiemetics', 'Antiemetics and Antinauseants', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 3 Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB00952,Naratriptan,Naratriptanis a 5-HT1B/1D receptor agonist used to treat migraines.,"['P08908', 'P28221', 'P28222', 'P30939']","Naratriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonist. Naratriptan has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3or 5-HT4receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Naratriptan also activates 5-HT1receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Naratriptan in humans.",CNS(=O)(=O)CCC1=CC2=C(NC=C2C2CCN(C)CC2)C=C1,"Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: () stimulation of presynaptic -HTD receptors, which serves to inhibit both dural vasodilation and inflammation; () direct inhibition of trigeminal nuclei cell excitability via -HTB/D receptor agonism in the brainstem and () vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular -HTB receptor agonism.TargetActionsOrganismA-hydroxytryptamine receptor AagonistHumansA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor FagonistHumans",[],"['Agents that produce hypertension', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Biogenic Amines', 'Biogenic Monoamines', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Monoamine Oxidase A Substrates', 'Nervous System', 'Neurotransmitter Agents', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Triptans', 'Vasoconstrictor Agents']" +DB00956,Hydrocodone,Hydrocodoneis an opioid agonist used as an analgesic and antitussive agent.,"['P35372', 'P41143', 'Q99720']","Hydrocodone inhibits pain signaling in both the spinal cord and brain12. Its actions in the brain also produce euphoria, respiratory depression, and sedation.",[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CCC2=O,"Hydrocodone binds to the mu opioid receptor (MOR) with the highest affinity followed by the delta opioid receptors (DOR).Hydrocodone's agonist effect at the MOR is considered to contribute the most to its analgesic effects. Both MOR and DOR are Gi/o coupled and and produces its signal through activation of inward rectifier potassium (GIRK) channels, inhibition of voltage gated calcium channel opening, and decreased adenylyl cyclase activity.In the dorsal horn of the spinal cord, activation of pre-synaptic MOR on primary afferents the inhibition of calcium channel opening and increased activity of GIRK channels hyperpolarizes the neuron and prevents release of neurotransmitters. Post-synaptic MOR can also prevent activation of neurons by glutamate through the aforementioned mechanisms.Hydrocodone can also produce several actions in the brain similarly to other opioids. +Activation of MOR in the periaquaductal gray (PAG) inhibits the GABAergic tone on medulo-spinal neurons.,This allows these neurons, which project to the dorsal horn of the spinal cord, to suppress pain signalling in secondary afferents by activating inhibitory interneurons. MOR can also inhibit GABAergic neurons in the ventral tegmental area, removing the inhibitory tone on dopaminergic neurons in the nucleus accumbens and contributing to the activation of the brain's reward and addiction pathway. The inhibitory action or MOR likely contributes to respiratory depression, sedation, and suppression of the cough reflex.Activation of DOR may contribute to analgesia through the above mechanisms but has not been well studied.TargetActionsOrganismAMu-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansUSigma non-opioid intracellular receptor ligandHumans",[],"['Alkaloids', 'Analgesics', 'Antitussive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cough and Cold Preparations', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Opiate Alkaloids', 'Opioid Agonist', 'Opioids', 'Opium Alkaloids and Derivatives', 'Peripheral Nervous System Agents', 'Respiratory System Agents', 'Semi-synthetic Opioids', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB01348,Spirapril,Spirapril is an ACE inhibitor antihypertensive drug used to treat hypertension. Spirapril is converted to the active spiraprilat after administration. ACE inhibitors are used primarily in treatment of hypertension and congestive heart failure.,['P12821'],"Spirapril is an angiotensin-converting enzyme (ACE) inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. By blocking ACE, spirapril decreases angiotensin II which is a vasoconstrictor and inducer of aldosterone. So by inhibiting the enzymes, aldosterone secreation is decreased (so less sodium is reabsorbed) and there is a decrease in vasoconstriction. Combined, this leades to a decrease in blood pressure.",CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2(C[C@H]1C(O)=O)SCCS2,"Spiraprilat, the active metabolite of spirapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Spiraprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Amino Acids, Peptides, and Proteins', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Dipeptides', 'Enzyme Inhibitors', 'Oligopeptides', 'Peptides', 'Protease Inhibitors']" +DB01416,Cefpodoxime,"Cefpodoximeis a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including gonorrhea, community acquired pneumonia, and sinusitis.",['P0AD68'],"Cefpodoxime is shown to be effective against most Gram positive and Gram negative bacteria, exceptPseudomonas aeruginosa,Enterococcus, andBacteroides fragilis.",[H][C@]12SCC(COC)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O,"Cefpodoxime is active against a wide spectrum of Gram-positive and Gram-negative bacteria. Cefpodoxime is stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and cephalosporins, due to their production of beta-lactamase, may be susceptible to cefpodoxime. Cefpodoxime is inactivated by certain extended spectrum beta-lactamases. The bactericidal activity of cefpodoxime results from its inhibition of cell wall synthesis. The active metabolite of cefpodoxime binds preferentially to penicillin binding protein , which inhibits production of peptidoglycan, the primary constituent of bacterial cell walls.TargetActionsOrganismAPeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta Lactam Antibiotics', 'beta-Lactams', 'Cefpodoxime', 'Cephacetrile', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Prodrugs', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00771,Clidinium,"Clidiniumis a synthetic anticholinergic used to treat peptic ulcer disease, colicky abdominal pain, diverticulitis, and IBS.",['P11229'],Clidinium is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract.,C[N@@+]12CC[C@@H](CC1)C(C2)OC(=O)C(O)(C1=CC=CC=C1)C1=CC=CC=C1,Inhibits muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites primarily by inhibiting the M muscarinic receptors.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumans,[],"['Acids, Carbocyclic', 'Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Anticholinergic Agents', 'Autonomic Agents', 'Benzilates', 'Central Nervous System Depressants', 'Decreased Parasympathetic Acetylcholine Activity', 'Digestive/GI System Activity Alteration', 'Diphenylacetic Acids', 'Drugs for Functional Gastrointestinal Disorders', 'GI Motility Alteration', 'Hydroxy Acids', 'Muscarinic Antagonists', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Phenylacetates', 'Quinuclidines']" +DB00828,Fosfomycin,Fosfomycinis a broad spectrum antibiotic used to treat uncomplicated urinary tract infections.,['P0A749'],"Although used primarily to treat urinary tract infections, fosfomycin has been shown to act synergistically with other antibiotics against clinically relevant bacteria.1There is also growing interest in the potential of fosfomycin to treat more complex infections since it has retained activity against many difficult-to-treat strains of bacteria including methicillin-resistantStaphylococcus aureus(MRSA) and multidrug-resistant enterobacteria.7Further, since fosfomycin has a unique and singular mechanism of action, the risk of cross-resistance with other antibiotics is low.6,5Fosfomycin also demonstrates immunomodulating properties. For example, the antibiotic may influence components of the acute inflammatory cytokine response and enhances neutrophil phagocytic destruction of pathogens.1,4Fosfomycin penetrates biofilms effectively and is capable of not only reducing or eliminating microorganisms in biofilms but can also alter the biofilm structure.1,7",C[C@@H]1O[C@@H]1P(O)(O)=O,"Fosfomycin exerts its bactericidal effects by binding covalently to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme, rendering it inactive. By preventing MurA from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), fosfomycin inhibits the production of the peptidoglycan precursor UDP N-acetylmuramic acid (UDP-MurNAc).,Ultimately, the first step of bacterial cell wall synthesis is disrupted.InEscherichia coli, fosfomycin gains entry into bacterial cells via two mechanisms: the L-alpha-glycerophosphate system and the hexose--phosphate transporter system.Fosfomycin also has important effects on cell adhesion. For example, the adhesion of bacterial cells to urinary epithelial cells is reduced in the presence of fosfomycin. The adhesion ofStreptococcus pneumoniaeandHaemophilus influenzaeto respiratory epithelial cells is also reducedTargetActionsOrganismAUDP-N-acetylglucosamine -carboxyvinyltransferaseinhibitorEscherichia coli (strain K)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Drugs that are Mainly Renally Excreted', 'Organophosphonates', 'Organophosphorus Compounds', 'Otologicals', 'Sensory Organs']" +DB01421,Paromomycin,"Paromomycinis an aminoglycoside antibiotic used in the treatment of acute and chronic intestinal amebiasis, and as an adjunct for the management of hepatic coma.","['Q5SHN7', 'P08865', 'Q96L21']",Paromomycin is a broad spectrum aminoglycoside antibiotic produced byStreptomyces rimosusvar. paromomycinus. The in vitro and in vivo antibacterial action of paromomycin closely parallels that of neomycin.,NC[C@@H]1O[C@H](O[C@@H]2[C@@H](CO)O[C@@H](O[C@@H]3[C@@H](O)[C@H](N)C[C@H](N)[C@H]3O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3N)[C@@H]2O)[C@H](N)[C@@H](O)[C@@H]1O,"Paromomycin inhibits protein synthesis by binding to S ribosomal RNA. Bacterial proteins are synthesized by ribosomal RNA complexes which are composed of subunits, a large subunit (s) and small (s) subunit, which forms a s ribosomal subunit. tRNA binds to the top of this ribosomal structure. Paramomycin binds to the A site, which causes defective polypeptide chains to be produced. Continuous production of defective proteins eventually leads to bacterial death.TargetActionsOrganismAS ribosomal protein SinhibitorThermus thermophilus (strain HB / ATCC / DSM )AS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaAS ribosomal protein SAinhibitorHumansAS ribosomal protein L-likeinhibitorHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Amebicides', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Antiparasitic Agents', 'Antiprotozoals', 'Carbohydrates', 'Glycosides', 'Intestinal Antiinfectives', 'Nephrotoxic agents']" +DB04866,Halofuginone,"Halofuginone is a low molecular weight quinazolinone alkaloid, and a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also effectively suppresses tumor progression and metastasis in mice. Collgard Biopharmaceuticals is developing halofuginone for the treatment of scleroderma and received orphan drug designation from the U.S. Food and Drug Administration in March, 2000.","['P02452', 'P08253']","Halofuginone, a fully synthetic small molecule, is a potent and selective regulator of stromal cell activation, cell migration and Collagen type I synthesis, a process that has been identified as a 'master switch' in the body's tissue repair process.",[H][C@]1(O)CCCN[C@]1([H])CC(=O)CN1C=NC2=C(C=C(Cl)C(Br)=C2)C1=O,"Halofuginone is a potent inhibitor of collagen a(I) and matrix metalloproteinase (MMP-) gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. The profound antitumoral effect of halofuginone is attributed to its combined inhibition of the tumor stromal support, vascularization, invasiveness, and cell proliferation.TargetActionsOrganismUCollagen alpha-(I) chainNot AvailableHumansU kDa type IV collagenaseNot AvailableHumans",[],"['Angiogenesis Inhibitors', 'Angiogenesis Modulating Agents', 'Anti-Infective Agents', 'Antineoplastic Agents', 'Antiparasitic Agents', 'Antiprotozoals', 'Coccidiostats', 'Enzyme Inhibitors', 'Growth Inhibitors', 'Growth Substances', 'Heterocyclic Compounds, Fused-Ring', 'Protein Synthesis Inhibitors', 'Quinazolines']" +DB01108,Trilostane,Trilostane is an inhibitor of 3 beta-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome. It was withdrawn from the United States market in April 1994.,"['P14060', 'P26439', 'P03372', 'Q92731']","Trilostane blocks an enzyme involved in the production of several steroids including cortisol. Inhibiting this enzyme inhibits the production of cortisol. In Cushing's syndrome, the adrenal gland overproduces steroids. Although steroids are important for various functions of the body, too much can cause problems. Trilostane reduces the amount of steroids produced by the adrenal gland. This product was withdrawn from the U.S. market in April 1994.",[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]23O[C@@H]2C(O)=C(C[C@]13C)C#N,"Trilostane produces suppression of the adrenal cortex by inhibiting enzymatic conversion of steroids by -beta-hydroxysteroid dehydrogenase/delta , ketosteroid isomerase, thus blocking synthesis of adrenal steroids.TargetActionsOrganismA beta-hydroxysteroid dehydrogenase/Delta -->-isomerase type inhibitorHumansA beta-hydroxysteroid dehydrogenase/Delta -->-isomerase type inhibitorHumansAEstrogen receptor alphaallosteric modulatorHumansAEstrogen receptor betaallosteric modulatorHumans",[],"['Abortifacient Agents', 'Abortifacient Agents, Steroidal', 'Adrenal Cortex Hormones', 'Androstanes', 'Androstanols', 'Antiadrenal Preparations', 'Anticorticosteroids', 'Antineoplastic Agents', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Oxidative Phosphorylation Coupling Factors', 'Reproductive Control Agents', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Testosterone Congeners']" +DB08820,Ivacaftor,Ivacaftoris a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator used alone or in combination products to treat cystic fibrosis in patients who have specific genetic mutations that are responsive to the medication.,['P13569'],"The use of Ivacaftor has been shown to both improve CF symptoms and modulate underlying disease pathology. This is achieved by potentiating the channel opening probability (or gating) of CFTR protein in patients with impaired gating mechanisms. This is in contrast toLumacaftor, another CF medication, that functions by preventing misfolding of the CFTR protein and thereby results in increased processing and trafficking of mature protein to the cell surface.Results from clinical trials indicated that treatment with ivacaftor results in improved lung function, reduced chance of experiencing a pulmonary exacerbation, reduced sweat chloride, increased weight gain, and improvements in CF symptoms and quality of life.18When combined with tezacaftor, significant improvements in lung function have been observed in clinical studies.14Ivacaftor was not found to increase the QTc interval in a clinically significant manner.18Although ivacaftor given alone has not shown any significant improvements in patients with the delta-F508 mutation, it has shown significant improvements (>10% increase in FEV1 from baseline) in lung function for the following mutations: E56K, P67L, R74W, D110E, D110H, R117C, R117H, G178R, E193K, L206W, R347H, R352Q, A455E, S549N, S549R, G551D, G551S, D579G, S945L, S977F, F1052V, K1060T, A1067T, G1069R, R1070Q, R1070W, F1074L, D1152H, G1244E, S1251N, S1255P, D1270N, and G1349.18This list was expanded by the FDA in May 2017 from 10 to 33 to accommodate more rare mutations.13It is important to note that this drug may cause an increase in liver transaminases (ALT, AST). Ensure to assess liver transaminases before the initiation of treatment, every 3 months during the first year of administration, followed by every year thereafter.18",CC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C,"A wide variety of CFTR mutations correlate to the Cystic Fibrosis phenotype and are associated with differing levels of disease severity. The most common mutation, affecting approximately % of patients with CF worldwide, is known as Fdel-CFTR or delta-F (ΔF), in which a deletion in the amino acid phenylalanine at position results in impaired production of the CFTR protein, thereby causing a significant reduction in the amount of ion transporter present on cell membranes.Ivacaftor as monotherapy has failed to show a benefit for patients with delta-F mutations, most likely due to an insufficient amount of protein available at the cell membrane for interaction and potentiation by the drug.The next most common mutation, GD, affecting -% of CF patients worldwide is characterized as a missense mutation, whereby there is sufficient amount of protein at the cell surface, but opening and closing mechanisms of the channel are altered.Ivacaftor is indicated for the management of CF in patients with this second type of mutation, as it binds to and potentiates the channel opening ability of CFTR proteins on the cell membrane.Ivacaftor exerts its effect by acting as a potentiator of the CFTR protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes of the lungs, pancreas, and other organs. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes,. Ivacaftor improves CF symptoms and underlying disease pathology by potentiating the channel open probability (or gating) of CFTR protein in patients with impaired CFTR gating mechanisms. The overall level of ivacaftor-mediated CFTR chloride transport is dependent on the amount of CFTR protein at the cell surface and how responsive a particular mutant CFTR protein is to ivacaftor potentiation.TargetActionsOrganismACystic fibrosis transmembrane conductance regulatorpotentiatorHumans",[],"['Amines', 'Aniline Compounds', 'Benzene Derivatives', 'Chloride Channel Activation Potentiators', 'Chloride Channel Agonists', 'Cystic Fibrosis Transmembrane Conductance Regulator Potentiators', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (weak)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Membrane Transport Modulators', 'P-glycoprotein inhibitors', 'Phenols', 'Quinolines']" +DB00419,Miglustat,Miglustatis a glucosylceramide synthase inhibitor used for the management of mild to moderate type I Gaucher disease for patients who are not candidates for whole enzyme replacement.,['Q16739'],"Miglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures.",CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO,"Miglustat functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids. The goal of treatment with miglustat is to reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to a level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy), reducing the accumulation of glucocerebroside in macrophages. In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids. In clinical trials, miglustat improved liver and spleen volume, as well as hemoglobin concentration and platelet count. Inhibition of glycosphingolipid synthesis has also shown to reduce intracellular lipid storage, improve fluid-phase endosomal uptake and normalize lipid transport in peripheral blood B lymphocytes of NP-C patients, which results in a decrease in the potentially neurotoxic accumulation of gnagliosides GMand GM, lactosylceramide and glucosylceramide, possibly preventing further neuronal damage. Other studies have also suggested that miglustat may indirectly modulate intracellular calcium homeostasis through its effects on glucosylceramide levels, and evidence has shown that an initiating factor in the pathogenesis of NP-C may be impaired calcium homeostasis related to sphingosine storage. Therefore, the effect that miglustat exerts on intracellular calcium levels may influence an important underlying pathogenic mechanism of NP-C.TargetActionsOrganismACeramide glucosyltransferaseinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Alkaloids', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Carbohydrates', 'Enzyme Inhibitors', 'Gaucher Disease', 'Glucosylceramide Synthase Inhibitor', 'Glucosylceramide Synthase Inhibitors', 'Glycoside Hydrolase Inhibitors', 'Imines', 'Imino Pyranoses', 'Imino Sugars', 'Other Miscellaneous Therapeutic Agents', 'Piperidines', 'Various Alimentary Tract and Metabolism Products']" +DB01600,Tiaprofenic acid,Tiaprofenic acidis a nonsteroidal anti-inflammatory (NSAID) used to manage inflammation and analgesia associated with rheumatoid arthritis and osteoarthritis.,"['P23219', 'P35354']","Tiaprofenic acid is a non-steroidal anti-inflammatory drug of the arylpropionic acid (profen) class, used to treat pain, especially arthritic pain. The typical adult dose is 300mg twice daily. This drug is not recommended for use in the pediatric population.",CC(C(O)=O)C1=CC=C(S1)C(=O)C1=CC=CC=C1,"Tiaprofenic acid belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). It works by blocking the production of a chemical (prostaglandin) which the body produces in response to injury or certain diseases. This prostaglandin would otherwise go on to cause swelling, pain and inflammation.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Acyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Fatty Acids', 'Fatty Acids, Volatile', 'Lipids', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Other Nonsteroidal Anti-inflammatory Agents', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Propionates', 'Prostaglandin Antagonists', 'Sensory System Agents']" +DB00978,Lomefloxacin,Lomefloxacinis a fluoroquinolone used to prevent and treat a wide variety of infections in the body.,"['P43700', 'P43702', 'P11388']","Lomefloxacin is a fluoroquinolone antibiotic used to treat chronic bronchitis, as well as complicated and uncomplicated urinary tract infections. It is also used as a prophylactic or preventative treatment to prevent urinary tract infections in patients undergoing transrectal or transurethral surgical procedures. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such asE.coliandNeisseria gonorrhoeaas well as gram-positive bacteria includingS. pneumoniaeandStaphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.",CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N3CCNC(C)C3)C(F)=C12,"Lomefloxacin is a bactericidal fluoroquinolone agent with activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of lomefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)UDNA topoisomerase -alphainhibitorHumans",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Fluoroquinolone Antibacterial', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'Ophthalmologicals', 'Photosensitizing Agents', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Sensory Organs', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00452,Framycetin,"Framycetinis an aminoglycoside antibiotic used in various formulations and combinations with other agents to treat hemorrhoids, eye and ear infections, and to reduce nasal carriage of staphylococcus.","['P0A7S3', 'P61073']","Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria.",NC[C@@H]1O[C@H](O[C@@H]2[C@@H](CO)O[C@@H](O[C@@H]3[C@@H](O)[C@H](N)C[C@H](N)[C@H]3O[C@H]3O[C@H](CN)[C@@H](O)[C@H](O)[C@H]3N)[C@@H]2O)[C@H](N)[C@@H](O)[C@@H]1O,"Framycetin binds to specific S-subunit proteins and S rRNA, four nucleotides of S rRNA and a single amino acid of protein S. This interferes with decoding site in the vicinity of nucleotide in S rRNA of S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.TargetActionsOrganismAS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaAS ribosomal protein SinhibitorEscherichia coli (strain K)UC-X-C chemokine receptor type antagonistHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Carbohydrates', 'Dermatologicals', 'Glycosides', 'Medicated Dressings', 'Medicated Dressings With Antiinfectives', 'Nasal Preparations', 'Nephrotoxic agents', 'Ophthalmologicals', 'Sensory Organs']" +DB04842,Fluspirilene,Fluspirileneis an antipsychotic agent used in the treatment of schizophrenia.,"['P14416', 'P28223', 'Q06432']","Fluspirilene is a relatively long-acting injectable depot antipsychotic drug used for schizophrenia. Fluspirilene does not differ greatly from other depot antipsychotics (fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate) with respect to treatment efficacy, response or tolerability. Outcomes suggest that fluspirilene does not differ significantly from oral antipsychotics or in different weekly regimens, although much cannot be inferred because of the shortage of trials.",FC1=CC=C(C=C1)C(CCCN1CCC2(CC1)N(CNC2=O)C1=CC=CC=C1)C1=CC=C(F)C=C1,TargetActionsOrganismADopamine D receptorantagonistHumansU-hydroxytryptamine receptor AantagonistHumansUVoltage-dependent calcium channel gamma- subunitinhibitorHumans,['Antipsychotic Treatment'],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antidepressive Agents', 'Antipsychotic Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Diphenylbutylpiperidine Derivatives', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Imidazoles', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Piperidines', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Spiro Compounds', 'Tranquilizing Agents']" +DB11181,Homatropine,"Homatropineis an anticholinergic agent used to dilate the pupil, treat inflammation of the uveal tract, and suppress a cough.","['P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Homatropine is an anticholinergic drug that produces typical anticholinergic effects inducing mydriasis and cycloplegia. Other effects of structurally-related atropine that could also apply to homatropine include inhibition of secretions, tachycardia, relaxation of smooth muscle and central nervous effects including excitation1.",[H][C@]12CC[C@]([H])(C[C@@H](C1)OC(=O)C(O)C1=CC=CC=C1)N2C,"Homatropine is a competitive muscarinic receptor antagonist with a bulky aromatic group in place of the acetyl group of acetylcholine. It is expected to act in similar manner as atropine, producing similar parasympatholytic effects. By blocking muscarinic receptors and cholinergic signalling pathways, homatropine blocks the response of the iris sphincter muscle and cause the pupil to become unresponsive to light upon dilation or mydriasis. It also blocks the accommodative muscle of the ciliary body to cholinergic stimulation.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Alkaloids', 'Anticholinergic Agents', 'Autonomic Agents', 'Aza Compounds', 'Azabicyclo Compounds', 'Muscarinic Antagonists', 'Mydriatics and Cycloplegics', 'Ophthalmologicals', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Sensory Organs']" +DB06698,Betahistine,Betahistineis an antivertigo agent used for the reduction of episodes of vertigo association with Ménière's disease.,"['P35367', 'Q9Y5N1']","Through its actions on the histamine receptors, betahistine provides relief from vertigo associated with Ménière's disease.3,5,11",CNCCC1=CC=CC=N1,"Vertigo is a disturbing sensation of movement caused by dysfunction of the labyrinth (inner ear), vestibular nerve, cerebellum, brainstem, or Central Nervous System (CNS). Vestibular forms of vertigo are often accompanied by auditory dysfunctions such as hyperacusis, hearing loss, and tinnitus.In most cases, adaptive mechanisms of the CNS lead to functional recovery after episodes of vertigo, however, syndromes such as Ménière's disease tend to cause the recurrence of vertigo symptoms. This significantly impacts the quality of life and the ability to carry out daily activities.H-receptor activityThe mechanism of action of betahistine is multifactorial. Ménière's disease is thought to result from a disruption of endolymphatic fluid homeostasis in the ear.Betahistine mainly acts as a histamine H-receptor agonist. The stimulation of H-receptors in the inner ear causes a vasodilatory effect leading to increased permeability of blood vessels and a reduction in endolymphatic pressure; this action prevents the rupture of the labyrinth, which can contribute to the hearing loss associated with Ménière's disease. Betahistine is also purported to act by reducing the asymmetrical functioning of sensory vestibular organs and increasing vestibulocochlear blood flow, relieving symptoms of vertigo.H-receptor activityIn addition to the above mechanisms, betahistine also acts as a histamine H-receptor antagonist, increasing the turnover of histamine from postsynaptic histaminergic nerve receptors, subsequently leading to an increase in H-agonist activity. H-receptor antagonism elevates levels of neurotransmitters including serotonin in the brainstem, inhibiting the activity of vestibular nuclei, thus restoring proper balance and decreasing vertigo symptoms.TargetActionsOrganismAHistamine H receptoragonistHumansAHistamine H receptorantagonistHumans",[],"['Antivertigo Preparations', 'Histamine Agents', 'Histamine Agonists', 'Histamine Antagonists', 'Miscellaneous Central Nervous System Agents', 'Miscellaneous Therapeutic Agents', 'Nervous System', 'Neurotransmitter Agents', 'Pyridines', 'Vasodilating Agents']" +DB00913,Anileridine,Anileridineis an opioid analgesic used to treat moderate to severe pain.,['P35372'],"Anileridine, a potent analgesic, is an analog of pethidine. Anileridine is useful for the relief of moderate to severe pain. It may also be used as an analgesic adjunct in general anesthesia in the same manner as meperidine to reduce the amount of anesthetic needed, to facilitate relaxation, and to reduce laryngospasm. In addition, anileridine exerts mild antihistaminic, spasmolytic and antitussive effects. Anileridine's main pharmacologic action is exerted on the CNS. Respiratory depression, when it occurs, is of shorter duration than that seen with morphine or meperidine when equipotent analgesic doses are used.",CCOC(=O)C1(CCN(CCC2=CC=C(N)C=C2)CC1)C1=CC=CC=C1,"Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Opioids such as anileridine close N-type voltage-operated calcium channels (OP-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP and OP receptor agonist). This results in hyperpolarization and reduced neuronal excitability.TargetActionsOrganismAMu-type opioid receptoragonistHumans",[],"['Anesthetics', 'Anesthetics, General', 'Nervous System', 'Opioid Anesthetics', 'Piperidines']" +DB01093,Dimethyl sulfoxide,"Dimethyl sulfoxideis a reversible mitogen-activated extracellular signal-regulated kinase-1 (MEK1) and MEK2 inhibitor used to treat certain types of melanoma, metastatic non-small cell lung cancer, and locally advanced or metastatic anaplastic thyroid cancer.","['Q01344', 'Q8WXI7', 'P01106']","Dimethyl Sulfoxide may have anti-inflammatory, antioxidant and analgesic activities. Dimethyl Sulfoxide also readily penetrates cellular membranes. The membrane-penetrating ability of dimethyl sulfoxide may enhance diffusion of other substances through the skin. For this reason, mixtures of idoxuridine and dimethyl sulfoxide have been used for topical treatment of herpes zoster in the United Kingdom.",CS(C)=O,"The mechanism of dimethyl sulfoxide's actions is not well understood. Dimethyl sulfoxide has demonstrated antioxidant activity in certain biological settings. For example, the cardiovascular protective effect of dimethyl sulfoxide in copper-deficient rats is thought to occur by an antioxidant mechanism. It is also thought that dimethyl sulfoxide's possible anti-inflammatory activity is due to antioxidant action.TargetActionsOrganismUInterleukin- receptor subunit alphadownregulatorHumansUMucin-downregulatorHumansUMyc proto-oncogene proteindownregulatorHumans",['Extravasation of chemotherapy drugs'],"['Antioxidants', 'Compounds used in a research, industrial, or household setting', 'Cryoprotective Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Free Radical Scavengers', 'Genito Urinary System and Sex Hormones', 'Kinase Inhibitor', 'Miscellaneous Therapeutic Agents', 'Musculo-Skeletal System', 'Protective Agents', 'Solvents', 'Sulfoxides', 'Sulfur Compounds', 'Topical Products for Joint and Muscular Pain', 'Urologicals']" +DB09068,Vortioxetine,Vortioxetineis a serotonin modulating antidepressant indicated for the treatment of major depressive disorder (MDD).,"['P31645', 'P46098', 'P34969', 'P28222', 'P08908', 'P08588', 'P23975']","Vortioxetine binds with high affinity to the human serotonin transporter (Ki=1.6 nM), but not to the norepinephrine (Ki=113 nM) or dopamine (Ki>1000 nM) transporters. Vortioxetine potently and selectively inhibits reuptake of serotonin by inhibition of the serotonin transporter (IC50=5.4 nM). Specifically, vortioxetine binds to 5­HT3 (Ki=3.7 nM), 5­HT1A (Ki=15 nM), 5­HT7 (Ki=19 nM), 5­HT1D (Ki=54 nM), and 5­HT1B (Ki=33 nM), receptors and is a 5­HT3, 5­HT1D, and 5­HT7 receptor antagonist, 5­HT1B receptor partial agonist, and 5­HT1A receptor agonist.",CC1=CC=C(SC2=CC=CC=C2N2CCNCC2)C(C)=C1,"Vortioxetine is classified as a serotonin modulator and simulator (SMS) as it has a multimodal mechanism of action towards the serotonin neurotransmitter system whereby it simultaneously modulates one or more serotonin receptors and inhibits the reuptake of serotonin. More specifically, vortioxetine acts via the following biological mechanisms: as a serotonin reuptake inhibitor (SRI) through inhibition of the serotonin transporter, while also acting as a partial agonist of the -HTB receptor, an agonist of -HTA, and antagonist of the -HT, -HTD, and -HT receptors.TargetActionsOrganismASodium-dependent serotonin transporterinhibitorHumansA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor antagonistHumansA-hydroxytryptamine receptor Bpartial agonistHumansA-hydroxytryptamine receptor AagonistHumansUBeta- adrenergic receptorligandHumansUSodium-dependent noradrenaline transporterblockerHumans",[],"['Agents that produce hypertension', 'Anti-Anxiety Agents', 'Antidepressive Agents', 'Antidepressive Agents Indicated for Depression', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Membrane Transport Modulators', 'Nervous System', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors', 'Piperazines', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin Receptor Antagonists', 'Tranquilizing Agents']" +DB06594,Agomelatine,"Agomelatine is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors, tested in an animal model of depression. Agomelatine was developed in Europe by Servier Laboratories Ltd. and submitted to the European Medicines Agency (EMA) in 2005. The Committee for Medical Products for Human Use (CHMP) recommended refusal of marketing authorization on 27 July 2006. The major concern was that efficacy had not been sufficiently shown. In 2006 Servier sold the rights to develop Agomelatine in the US to Novartis.","['P28335', 'P48039', 'P49286']","Agomelatine resynchronises circadian rhythms in animal models of delayed sleep phase syndrome and other circadian rhythm disruptions. It increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin. Agomelatine has shown an antidepressant-like effect in animal depression models, (learned helplessness test, despair test, and chronic mild stress) circadian rhythm desynchronisation, and in stress and anxiety models. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset. Controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression",COC1=CC2=C(CCNC(C)=O)C=CC=C2C=C1,"The novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors (MT and MT) and as an antagonist at serotonin (-HT)(C) receptors.TargetActionsOrganismA-hydroxytryptamine receptor CantagonistHumansAMelatonin receptor type AagonistHumansAMelatonin receptor type BagonistHumans",[],"['Acetates', 'Acids, Acyclic', 'Amides', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Melatonin, agonists', 'Nervous System', 'Psychoanaleptics', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB01021,Trichlormethiazide,"A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)","['P55017', 'P05023', 'P00915', 'P00918', 'P22748']","Trichloromethiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Trichloromethiazide has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomer-ulonephritis, and chronic renal failure. Trichloromethiazide is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Like other thiazides, Trichloromethiazide promotes water loss from the body (diuretics). They inhibit Na+/Cl-reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.",NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C(Cl)Cl,"Trichlormethiazide seemingly appears to inhibit the active reabsorption of chloride in the ascending loop of Henle. Additionally, it may also do the same for sodium. These actions subsequently alter electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, Trichloromethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like Trichloromethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of Trichloromethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.TargetActionsOrganismASolute carrier family member inhibitorHumansASodium/potassium-transporting ATPase subunit alpha-inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Antihypertensive Agents', 'Benzothiadiazines', 'Cardiovascular Agents', 'Diuretics', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Low-Ceiling Diuretics and Potassium-Sparing Agents', 'Membrane Transport Modulators', 'Natriuretic Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB09245,Toloxatone,"Toloxatone is an antidepressant agent, the first ever use of which was in France, 1984. It acts as a selective and reversible inhibitor of monoamine oxidase-A (MOA)5.",['P21397'],"This drug has been shown to help manage the symptoms of depression by maintaining neuro-synaptic levels of serotonin and catecholamines while regulating their metabolism, which leads to relief of depressive symptoms1.",CC1=CC(=CC=C1)N1CC(CO)OC1=O,"This medication is a reversible inhibitor of monoamine oxidase type-A (also known as RIMA).MAO-A can be found in norepinephrinergic and serotonergic neurons and regulates the metabolism of serotonin and catecholamines, allowing for increased circulation in the synaptic cleft. +Traditional monoamine oxidase inhibitors irreversibly inhibit monoamine oxidase and therefore, side effects, drug interactions, and food interactions persist as long as - weeks after discontinuing toloxatone. The elevation of serotonin and norepinephrine levels occurs rapidly after medication administration. However, the therapeutic relief of depressive symptoms requires weeks of daily treatment to observe results. Selective and reversible MAO-A inhibitors are more effective in treating major depression without several of the drug and food interactions associated with traditional monoamine oxidase inhibitors.TargetActionsOrganismUAmine oxidase [flavin-containing] AantagonistHumans",[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Monoamine Oxidase A Inhibitors', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Nervous System', 'Oxazoles', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB09194,Etoperidone,Etoperidone is an atypical antidepressant introduced in Europe in 1977. It is a phenylpiperazine-substituted triazole derivative with a composition that classifies it as an analog of tradozone and presents a similar pharmacological profile.7Etoperidone was developed by Angelini Francesco ACRAF.2,"['P28223', 'P28335', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'P14416', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Etoperidone has a biphasic effect on the central transmission of serotonin.7It presents the capacity to inhibit serotonin receptor but also to inhibit the reuptake of serotonin, norepinephrine and dopamine.8As part of its actions, etoperidone also inhibits the α-adrenergic receptors which directly corresponds to the sedative and cardiovascular effects.7,10The presence of both effects caused that the effective dose of etoperidone was poorly tolerated thus, efforts have been made to separate the serotonergic and adrenergic functions in order to generate etoperidone-derivatives like nefazodone.10",CCN1C(=O)N(CCCN2CCN(CC2)C2=CC=CC(Cl)=C2)N=C1CC,The activity of etoperidone is made mainly by its major metabolite -('-chlorophenyl)piperazine (mCPP). mCPP binds with different affinity to most of the serotonergic receptors and adrenergic receptors. This metabolite is an agonist of -HTc and an antagonist of -HTa. Part of etoperidone structure contibutes to the activity in the α-adrenergic receptors.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumansA-hydroxytryptamine receptor CagonistHumansUAlpha- adrenergic receptorsantagonistHumansUAlpha- adrenergic receptorsantagonistHumansUDopamine D receptorantagonistHumansUMuscarinic acetylcholine receptorantagonistHumans,[],"['Antidepressive Agents', 'Central Nervous System Depressants', 'Combined Inhibitors of Serotonin/Norepinephrine Reuptake', 'Drugs that are Mainly Renally Excreted', 'Nervous System', 'Piperazines', 'Psychoanaleptics', 'Pyridines', 'Pyridones', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Antagonists']" +DB01553,Cloxazolam,"Cloxazolam is a benzodiazepine with anxiolytic, sedative/hypnotic, muscle relaxant, and antiepileptic effects. It is marketed in the Argentina, Australia, Portugal, Belgium, Switzerland, Luxembourg, Germany, Taiwan and Japan -- mainly for anti-anxiety. The usual dose of cloxazolam in adults is 3-12mg/day for anti-anxiety. Although less commonly noted, it has also been reported as clinically effective in the treatment of depression, schizophrenia, and neurosis. As well, it has also been studied in Japan in doses of 15-30mg/day as an adjunct in the treatment of intractable epilepsy, for which it has demonstrated effectiveness.","['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Studies have shown a superiority of 4mg/day of cloxazepam to 12mg/day of bromazepam in terms of anxiety, depressed mood, and sleep; an insignificant difference in terms of sedative effect; and less muscle relaxant effects. [3]Cloxazolam, administered as a single oral dose of 3mg, when compared to a single 5 mg dose of diazepam in one study, showed similar subjective measures; however, there cloxazolam caused more fatigue, and less mood improvement. Cloxazolam also induced a significant increase in heart rate in the control group of this study. [3]",ClC1=CC2=C(NC(=O)CN3CCOC23C2=CC=CC=C2Cl)C=C1,"Cloxazolam is a long acting benzodiazepine. It acts as a prodrug, with pharmacologically active metabolites, which bind to to the GABAa receptor, which other benzodiazepines bind to, to illicit a physiological response. [wiki]TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Psycholeptics']" +DB01559,Clotiazepam,Clotiazepamis a thienodiazepine used to manage anxiety disorders and insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Clotiazepam is a thienodiazepine possessing anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It increases the stage 2 non-rapid eye movement sleep.",CCC1=CC2=C(S1)N(C)C(=O)CN=C2C1=CC=CC=C1Cl,"Clotiazepam acts at the benzodiazepine receptors (BZD). This agonizes the action of GABA, increasing the frequency of opening of the channel chlorinates and penetration of the ions chlorinates through the ionophore. Increase in membrane polarization decreases the probability of discharge of neurons.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Anti-Anxiety Agents', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C18 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Nervous System', 'Psycholeptics']" +DB14533,Zinc chloride,Zinc chlorideis a medication used to treat zinc deficiencies and associated symptoms and also in total parenteral nutrition.,"['P46663', 'P16455', 'P04075', 'P68104', 'P06733', 'O14556', 'P15531', 'P07237', 'P30101', 'Q06830', 'P78330', 'P60174', 'P49411', 'P03372', 'P08700', 'P02795', 'O14618', 'Q13547', 'P56524', 'P29372', 'P04279', 'P00441', 'Q9BY41', 'O15304', 'P23415', 'Q00987', 'P01308', 'P46939', 'P45381', 'P05109', 'P06702', 'P14780', 'O15350', 'P29034', 'P04637', 'P25713', 'P04731', 'P01023', 'P02765', 'P02647', 'Q0VD83', 'P02649', 'O14791', 'P02746', 'P02747', 'P00736', 'P09871', 'P01024', 'P0C0L5', 'P04003', 'P20851', 'P01031', 'P46736', 'P08603', 'P10909', 'P00450', 'P15169', 'P22792', 'P81605', 'P02671', 'P02751', 'P69905', 'P68871', 'P00738', 'P35858', 'P19827', 'P19823', 'Q06033', 'Q14624', 'P01591', 'P03952', 'P01042', 'P35527', 'P19652', 'Q96PD5', 'P27169', 'P20742', 'P31151', 'P49908', 'P01009', 'P01011', 'P08185', 'P05546', 'P04278', 'P02787', 'P02766', 'P04004', 'P51693', 'Q06481', 'P05067', 'P09874', 'P04114', 'P02790', 'P04196', 'P03951', 'P41238', 'Q02383']","Zinc is a cofactor in many enzymes and mediates a number of catalytic, structural, and regulatory roles in the body.6It has a wide therapeutic index and long duration of action, as most zinc in the body is reabsorbed.2,10Patients should be counselled regarding the risk of administration in patients with severe kidney dysfunction.11",[Cl-].[Cl-].[Zn++],"Zinc performs catalytic, structural, and regulatory roles in the body. Zinc is a component of approximately human proteins.Zinc is cytoprotective against reactive oxygen species mediated apoptosis through the action of metallothioneins.In a promyelocytic leukemia cell line, zinc enhances the up-regulation of A mRNA, which, via the TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of TNF-α, IL-β, and IL-.In patients with diarrhea, zinc restores mucosal barrier integrity, restores enterocyte brush-border enzyme activity, promotes the production of antibodies, and promotes the production of circulating lymphocytes against intestinal pathogens.Zinc also directly affects ion channels as a potassium channel blocker of cAMP-mediated chlorine secretion.Zinc deficiency decreases thymulin, inhibiting T-helper cell maturation and decreased Th- cytokines like IL-.Decreased IL- decreases the activity of NK cells and CD+ T cells.Zinc deficiency also leads to the generation of CD+ T cells, decreased NF-κB activation, decreased phosphorylation of IκB, and decreased binding of NF-κB to DNA.TargetActionsOrganismUB bradykinin receptoragonistHumansUMethylated-DNA--protein-cysteine methyltransferasestabilizationHumansUFructose-bisphosphate aldolase AligandHumansUElongation factor -alpha binderHumansUAlpha-enolasebinderHumansUGlyceraldehyde--phosphate dehydrogenase, testis-specificbinderHumansUNucleoside diphosphate kinase AinhibitorHumansUProtein disulfide-isomerasebinderHumansUProtein disulfide-isomerase AbinderHumansUPeroxiredoxin-binderHumansUPhosphoserine phosphatasebinderHumansUTriosephosphate isomerasebinderHumansUElongation factor Tu, mitochondrialcofactorHumansUEstrogen receptor alphabinderHumansUInterleukin-binderHumansUMetallothionein-cofactorHumansUCopper chaperone for superoxide dismutasecofactorHumansUHistone deacetylase cofactorHumansUHistone deacetylase cofactorHumansUDNA--methyladenine glycosylasecofactorHumansUSemenogelin-cofactorHumansUSuperoxide dismutase [Cu-Zn]cofactorHumansUHistone deacetylase cofactorHumansUApoptosis regulatory protein SivabinderHumansUGlycine receptor subunit alpha-inhibitorHumansUE ubiquitin-protein ligase MdmbinderHumansUInsulinstabilizationHumansUUtrophincofactorHumansUAspartoacylasecofactorHumansUProtein S-AregulatorHumansUProtein S-AregulatorHumansUMatrix metalloproteinase-binderHumansUTumor protein pchaperoneHumansUProtein S-AinactivatorregulatorHumansUCellular tumor antigen pchaperoneHumansUMetallothionein-cofactorHumansUMetallothionein-AbinderHumansUAlpha--macroglobulinligandHumansUAlpha--HS-glycoproteinchelatorHumansUApolipoprotein A-IinducerligandHumansUApolipoprotein B receptorinducerHumansUApolipoprotein EantagonistHumansUApolipoprotein LinhibitorHumansUComplement Cq subcomponent subunit BmodulatorHumansUComplement Cq subcomponent subunit CmodulatorHumansUComplement Cr subcomponentmodulatorHumansUComplement Cs subcomponentmodulatorHumansUComplement CinhibitorligandHumansUComplement C-BmodulatorHumansUCb-binding protein alpha chainmodulatorHumansUCb-binding protein beta chainmodulatorHumansUComplement CligandHumansULys--specific deubiquitinase BRCCcofactorHumansUComplement factor HligandHumansUClusterininducerHumansUCeruloplasminligandHumansUCarboxypeptidase N catalytic chaincofactorHumansUCarboxypeptidase N subunit cofactorHumansUDermcidinstabilizationHumansUFibrinogen alpha chainbinderHumansUFibronectinmodulatorligandHumansUHemoglobin subunit alphainducerHumansUHemoglobin subunit betainducerHumansUHaptoglobinbinderHumansUInsulin-like growth factor-binding protein complex acid labile subunitinducerHumansUInter-alpha-trypsin inhibitor heavy chain HbinderHumansUInter-alpha-trypsin inhibitor heavy chain HbinderHumansUInter-alpha-trypsin inhibitor heavy chain HbinderHumansUInter-alpha-trypsin inhibitor heavy chain HbinderHumansUImmunoglobulin J chaincomponent ofHumansUPlasma kallikreininhibitorHumansUKininogen-cofactorHumansUKeratin, type I cytoskeletal ligandHumansUAlpha--acid glycoprotein binderHumansUN-acetylmuramoyl-L-alanine amidasebinderHumansUSerum paraoxonase/arylesterase inducerHumansUPregnancy zone proteinbinderHumansUProtein S-AbinderHumansUSelenoprotein PbinderHumansUAlpha--antitrypsinligandHumansUAlpha--antichymotrypsinbinderHumansUCorticosteroid-binding globulinmodulatorHumansUHeparin cofactor agonistHumansUSex hormone-binding globulinmodulatorHumansUSerotransferrinligandHumansUTransthyretininducerHumansUVitronectininducerHumansUAmyloid-like protein ligandHumansUAmyloid-like protein ligandHumansUAmyloid beta A proteinligandHumansUPoly [ADP-ribose] polymerase component ofHumansUApolipoprotein B-ligandHumansUHemopexinligandHumansUHistidine-rich glycoproteincofactorHumansUCoagulation factor XIactivatorHumansUC->U-editing enzyme APOBEC-cofactorchelatorHumansUSemenogelin-cofactorHumans",['Dietary supplementation'],"['Acids', 'Acids, Noncarboxylic', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Anions', 'Basic Ointments and Protectants', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Chlorine Compounds', 'Compounds used in a research, industrial, or household setting', 'Cosmetics', 'Dental Agents', 'EENT Drugs, Miscellaneous', 'Electrolyte Solutions', 'Electrolytes', 'Household Products', 'I.V. Solution Additives', 'Ions', 'Metal cations', 'Metal divalent cations', 'Mouthwashes', 'Skin Ulcer, drug therapy', 'Vasoprotectives', 'Zinc Compounds']" +DB09244,Pirlindole,"This drug is classified as a reversible inhibitor of monoamine oxidase A enzyme (also known as a RIMA drug). It was developed and is currently used as an antidepressant in Russia. Its chemical structure is similar to metralindole, and it also shares pharmacological properties with this drug.","['P21397', 'P08908', 'P08913']","Pirlindole regulates that metabolism of norepinephrine and catecholamines, leading to relief of depressive symptoms. The prevention of breakdown of these neuromodulators is thought to elevate mood.",CC1=CC=C2N3CCNC4CCCC(=C34)C2=C1,This drug is a selective and reversible inhibitor of monoamine oxidase A (also known as MAO-A). Its main mechanism of action is selective and reversible inhibition of monoamine oxidase A. Its secondary mechanism of action is the inhibition effect of noradrenaline and -hydroxytryptamine reuptake.TargetActionsOrganismUAmine oxidase [flavin-containing] AantagonistHumansU-hydroxytryptamine receptor AantagonistHumansUAlpha-A adrenergic receptorantagonistHumans,[],"['Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Antidepressive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates', 'Monoamine Oxidase Inhibitors', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB00337,Pimecrolimus,Pimecrolimusis a topical calcineurin inhibitor used in the treatment of mild-moderate atopic dermatitis who are not candidates for other types of therapy due to previous lack of response or other reasons.,"['P42345', 'P62942']","Pimecrolimus is a chemical that is used to treat atopic dermatitis (eczema). Atopic dermatitis is a skin condition characterized by redness, itching, scaling and inflammation of the skin. The cause of atopic dermatitis is not known; however, scientists believe that it may be due to activation of the immune system by various environmental or emotional triggers. Scientists do not know exactly how pimecrolimus reduces the manifestations of atopic dermatitis, but pimecrolimus reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system. Pimecrolimus prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Pimecrolimus also reduces the ability of mast cells to release chemicals that promote inflammation.",[H][C@]1(CC[C@H](Cl)[C@@H](C1)OC)\C=C(/C)[C@@]1([H])OC(=O)[C@]2([H])CCCCN2C(=O)C(=O)[C@]2(O)O[C@@]([H])([C@H](C[C@H]2C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC)C(=O)C[C@H](O)[C@H]1C)OC,"Pimecrolimus binds with high affinity to macrophilin- (FKBP-) and inhibits the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin- and interferon gamma (Th-type) and Interleukin- and Interleukin- (Th-type) cytokine synthesis in human T cells. Also, pimecrolimus prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/lgE.TargetActionsOrganismASerine/threonine-protein kinase mTORpotentiatorHumansUPeptidyl-prolyl cis-trans isomerase FKBPApotentiatorHumans",[],"['Agents for Dermatitis, Excluding Corticosteroids', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Calcineurin Inhibitor Immunosuppressant', 'Calcineurin Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Enzyme Inhibitors', 'Immunologic Factors', 'Immunosuppressive Agents', 'Lactones', 'Misc. Skin and Mucous Membrane Agents', 'Peptidylprolyl Isomerase, antagonists & inhibitors', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB01061,Azlocillin,Azlocillin is a semisynthetic ampicillin-derived acylureido penicillin.,['Q8XJ01'],"Similar tomezlocillinandpiperacillin, azlocillin is an acylampicillin that exhibits an extended-spectrum of activity andin vitropotency that is greater than that of the carboxy penicillins. Azlocillin is shown to be effective against a broad spectrum of bacteria, includingPseudomonas aeruginosaand enterococci.",[H][C@](NC(=O)N1CCNC1=O)(C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@]12[H])C1=CC=CC=C1,"By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, azlocillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that azlocillin interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Agents that reduce seizure threshold', 'Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillin G', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB11994,Diacerein,Diacereinis an slow-onset anthraquinone IL-1 inhibitor used in the treatment of degenerative joint diseases like osteoarthritis.,"['Q13133', 'P55055', 'P09917', 'P05177', 'P08684', 'Q9HB55', 'P20815', 'P24462', 'P05181', 'P11712', 'P10635']",Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity345.,CC(=O)OC1=CC=CC2=C1C(=O)C1=C(OC(C)=O)C=C(C=C1C2=O)C(O)=O,"Diacerein's active metabolite rheinRheinreduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)- and - as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs. The anti-inflammatory action of rhein reduces the level of interleukin-beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism.TargetActionsOrganismUOxysterols receptor LXR-alphainhibitorHumansUOxysterols receptor LXR-betainhibitorHumansUArylamine N-acetyltransferaseinhibitorHelicobacter pyloriUArachidonate -lipoxygenaseinhibitorHumansUCytochrome P AinhibitorHumansUCytochrome P A SubfamilyinhibitorHumansUCytochrome P EinhibitorHumansUCytochrome P CinhibitorHumansUCytochrome P DinhibitorHumans",[],"['Anthracenes', 'Anti-Inflammatory Agents', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Musculo-Skeletal System', 'Quinones']" +DB11582,Thiocolchicoside,Thiocolchicosideis a semi-synthetic colchicine derivative used as an analgesic and anti-inflammatory.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P23415', 'O14788']","Thiocholchicoside is a muscle relaxing agent that works through selective binding to the GABA-A receptor. It prevents muscle contractions by activating the GABA inhibitory motor pathway18.This medication acts as a competitive GABA receptor antagonist and inhibits glycine receptors with similar potency as nicotinic acetylcholine receptors. It has powerful convulsant activity and should not be used in individuals at risk for seizures18,23.Used in combination with glafenine and meprobamate to tranquilize patients undergoing hysterosalpingography. In the treatment of painful muscle spasms. Thiocolchicoside acts both in contractures with a central cause and in contractures of reflex type, rheumatic and traumatic. It also alleviates symptoms of spastic sequelae of hemiparesis, Parkinson's disease and iatrogenic Parkinson symptoms, particularly neurodyslectic syndrome. Some other conditions that may benefit from this medication are acute and chronic lumbar and sciatic pain, cervico-brachial neuralgia, persistent torticollis, post-traumatic and post-operative pain18.",COC1=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C2CC[C@H](NC(C)=O)C3=CC(=O)C(SC)=CC=C3C2=C1OC,"Thiocolchicoside, is a synthetic sulfur derivative of colchicoside, a naturally occurring glucoside contained in the Colchicum autumnale plant. Thiocolchicoside has a selective and potent affinity for g-aminobutyric acid A (GABA-A) receptors and acts on muscular contractures by activating the GABA inhibitory pathways thereby behaving as a potent muscle relaxant. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. GABAergic neurons are involved in myorelaxation, anxiolytic treatment, sedation, and anesthetics. GABA can also modulate heart rate and blood pressure.It also has an affinity for the inhibitory glycine receptors (i.e., have glycomimetic and GABA mimetic activity), therefore acts as a muscle relaxant. Glycine is an inhibitory neurotransmitter and acts as an allosteric regulator of NMDA (N-methyl-D-aspartate) receptors. It is involved in the processing of motor and sensory data, thereby regulating movement, vision, and audition. Inhibitory neurotransmitter in spinal cord, allosteric regulator of NMDA receptors,.In one study, thiocolchicoside inhibited the function of recombinant human strychnine-sensitive glycine receptors composed of the alpha subunit with a potency (median inhibitory concentration of microM) lower than that apparent with recombinant GABA(A) receptors. The drug also inhibited the function of human nicotinic acetylcholine receptors made of the alpha and beta subunits, however, this effect was partial and moreover only apparent at high concentrations. Thiocolchicoside demonstrated no effect on the function of -HT(A) serotonin receptors.TargetActionsOrganismAGABA(A) ReceptorantagonistHumansUGlycine receptor subunit alpha-antagonistHumansUTumor necrosis factor ligand superfamily member antagonistHumans",[],"['Alkaloids', 'Central Nervous System Depressants', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System']" +DB01321,Josamycin,Josamycinis a macrolide antibiotic used for the treatment of various susceptible bacterial infections.,['P44345'],Josamycin is a macrolide antibiotic fromStreptomyces narbonensis. The drug has antimicrobial activity against a wide spectrum of pathogens.,CO[C@H]1[C@@H](CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@@H]1O[C@H](C)[C@@H](O[C@H]2C[C@@](C)(O)[C@@H](OC(=O)CC(C)C)[C@H](C)O2)[C@@H]([C@H]1O)N(C)C)OC(C)=O,"The mechanism of action of macrolides such as Josamycin is via inhibition of bacterial protein biosynthesis by binding reversibly to the subunit S of the bacterial ribosome, thereby inhibiting translocation of peptidyl tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations. Macrolides tend to accumulate within leukocytes, and are therefore actually transported into the site of infection.TargetActionsOrganismAS ribosomal protein LinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Lactones', 'Macrolides', 'Macrolides, Lincosamides and Streptogramins', 'Polyketides']" +DB01220,Rifaximin,"Rifaximinis a rifamycin-based non-systemic antibiotic used for the treatment of gastrointestinal bacterial infections, such as traveler's diarrhea and irritable bowel syndrome, and reduction of overt hepatic encephalopathy recurrence in adults.","['P0A8V2', 'O75469']","Rifaximin is a structural analog of rifampin and a non-systemic, gastrointestinal site-specific antibiotic. This non-systemic property of the drug is due to the addition of a pyridoimidazole ring, which renders it non-absorbable. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis and contributes to restore intestinal microflora imbalance. Other studies have also shown rifaximin to be an pregnane X receptor (PXR) activator. As PXR is responsible for inhibiting the proinflammatory transcription factor NF-kappa B (NF-κB) and is inhibited in inflammatory bowel disease (IBD), rifaximin was proven to be effective for the treatment of IBS-D.",CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C)C(O)=C4C(O)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C1=C(N=C5C=C(C)C=CN15)C4=C3C2=O,"Rifaximin acts by inhibiting RNA synthesis in susceptible bacteria by binding to the beta-subunit of bacterial deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase enzyme. This binding blocks translocation, which stops transcription.TargetActionsOrganismADNA-directed RNA polymerase subunit betainhibitorEscherichia coli (strain K)NNuclear receptor subfamily group I member agonistHumans",[],"['Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics for Topical Use', 'Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strong)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Intestinal Antiinfectives', 'Lactams, Macrocyclic', 'Rifamycin Antibacterial', 'Rifamycins']" +DB09285,Morniflumate,"Morniflumateis an NSAID derived from niflumic acid used in the symptomatic treatment of inflammatory conditions of the airways, ENT, and the urogenital and osteoarticular systems.","['P09917', 'P35354', 'Q15722', 'P21731']","Morniflumate, given at therapeutic dosages to healthy human volunteers, on leukotriene B4 (LTB4) and thromboxane (TXB2) synthesis, both in purified PMNs (polymorphnuclear neutrophils) and in whole blood1.In whole blood experiments, morniflumate reduced blood leukotriene B4 (LTB4) synthesis induced by Ca-ionophore A23187 Bx approximately 50%, both after a single dose and at steady state; the level of inhibition showed a pattern similar to the plasma levels of the bioactive metabolite of morniflumate (M1). The inhibition of serum thromboxane B2 (TXB2) levels was higher than 85%. Hence, morniflumate is demonstrated to reduce arachidonic acid metabolism, by exerting its effects on cyclooxygenase and 5-lipoxygenase. This characteristic might provide a better approach for anti-inflammatory therapy1.In several animal models orally administered morniflumate, the beta-morpholinoethyl ester of niflumic acid, proved almost equal to the parent compound in anti-inflammatory, analgesic and antipyretic activity with the absence of gastric irritating/ulcerogenic effects of its acidic parent compound7.",FC(F)(F)C1=CC(NC2=C(C=CC=N2)C(=O)OCCN2CCOCC2)=CC=C1,"The primary mechanism of niflumic acid and its ester is action is inhibition of enzymes involved in the synthesis of inflammatory prostaglandins. This medication inhibits cyclooxygenase and -lipoxygenase pathways, which lead to fever and inflammation.Niflumic acid, a calcium-activated Cl- channel blocker, is an analgesic and anti-inflammatory agent used in the treatment of inflammatory conditions. Niflumic acid does directly inhibit calcium channels or activate potassium channels. Niflumic acid selectively reduces noradrenaline- and -HT-induced pressor responses by inhibiting a mechanism which leads to the opening of voltage-gated calcium channels. Niflumic acid (NFA) produces biphasic behavior on human CLC-K channels that suggests the presence of two functionally different binding sites: an activating site and a blocking site.TargetActionsOrganismUArachidonate -lipoxygenaseantagonistHumansUProstaglandin G/H synthase Not AvailableHumansULeukotriene B receptor antagonistHumansUThromboxane A receptorNot AvailableHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Aminobenzoates', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Benzene Derivatives', 'Benzoates', 'Fenamates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Nicotinic Acids', 'ortho-Aminobenzoates', 'Pyridines', 'UGT1A9 Inhibitors']" +DB09019,Bromhexine,"Bromhexineis a mucolytic drug used to decrease the viscosity of mucus in the airway, enhancing mucus clearance.","['O15393', 'Q9BYF1']","Bromhexine thins airway secretions, improving breathing and discomfort associated with thick mucus in airways associated with a variety of respiratory conditions.1,11,13",CN(CC1=CC(Br)=CC(Br)=C1N)C1CCCCC1,"Inflammation of the airways, increased mucus secretion, and altered mucociliary clearance are the hallmarks of various diseases of the respiratory tract. Mucus clearance is necessary for lung health; bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract.Recent have studies have demonstrated that bromhexine inhibits the transmembrane serine protease receptor (TMPRSS) in humans. Activation of TMPRSS plays an important role in viral respiratory diseases such as influenza A and Middle East Respiratory Syndrome (MERS). Inhibition of receptor activation and viral entry by bromhexine may be effective in preventing or treating various respiratory illnesses, including COVID-.,In vitro studies have suggested the action of ambroxol (a metabolite of bromhexine) on the angiogensin-converting enzyme receptor (ACE), prevents entry of the viral envelope-anchored spike glycoprotein of SARS-Cov- into alveolar cells or increases the secretion of surfactant, preventing viral entry.,TargetActionsOrganismUTransmembrane protease serine Not AvailableHumansUAngiotensin-converting enzyme binderHumans",['Airway secretion clearance therapy'],"['Amines', 'Aniline Compounds', 'Cough and Cold Preparations', 'Cyclohexanes', 'Cyclohexylamines', 'Cycloparaffins', 'Expectorants', 'Respiratory System Agents']" +DB09093,Chlortetracycline,Chlortetracyclineis the first tetracycline antibiotic most commonly used for veterinary purposes.,"['P0A7V3', 'P0A7W7', 'P0A7U3', 'P0AG59', 'P02359', 'P84077', 'P29422', 'P54762', 'P16233', 'Q9UM07']",Tetracycline antibiotics are bacteriostatic agents which act to inhibit bacterial growth and reproduction2.,[H][C@@]12C[C@@]3([H])C(=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C)C(=O)C1=C(O)C=CC(Cl)=C1[C@@]3(C)O,"Chlortetracycline, like other tetracyclines, competes for the A site of the bacterial ribosome. This binding competes with tRNA carrying amino acids preventing the addition of more amino acids to the peptide chain. This inhibition of protein synthesis ultimately inhibits growth and reproduction of the bacterial cell as necessary proteins cannot be synthesized.TargetActionsOrganismAS ribosomal RNAinhibitorEnteric bacteria and other eubacteriaAS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)AS ribosomal protein SinhibitorEscherichia coli (strain K)UADP-ribosylation factor inhibitorHumansUCatalaseinhibitorMicrococcus luteusUEphrin type-B receptor inhibitorHumansUPancreatic triacylglycerol lipaseinhibitorHumansUProtein-arginine deiminase type-inhibitorHumans",[],"['Agents that produce neuromuscular block (indirect)', 'Alimentary Tract and Metabolism', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antibiotics for Topical Use', 'Antiinfectives and Antiseptics for Local Oral Treatment', 'Antiinfectives for Systemic Use', 'Antiparasitic Agents', 'Antiprotozoals', 'Dermatologicals', 'Enzyme Inhibitors', 'Naphthacenes', 'Ophthalmologicals', 'Protein Synthesis Inhibitors', 'Sensory Organs', 'Stomatological Preparations', 'Tetracyclines']" +DB01012,Cinacalcet,Cinacalcetis a calcium sensing receptor agonist used to treat secondary hyperparathyroidism in chronic kidney disease and hypercalcemia in parathyroid carcinoma.,['P41180'],"Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. In CKD patients on dialysis with uncontrolled secondary HPT, reductions in PTH are associated with a favorable impact on bone-specific alkaline phosphatase (BALP), bone turnover and bone fibrosis. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.",C[C@@H](NCCCC1=CC(=CC=C1)C(F)(F)F)C1=CC=CC2=CC=CC=C12,"Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.TargetActionsOrganismAExtracellular calcium-sensing receptoragonistHumans",[],"['Anti-Parathyroid Agents', 'Calcimimetic Agents', 'Calcium Homeostasis', 'Calcium-Regulating Hormones and Agents', 'Calcium-sensing Receptor Agonist', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Increased Calcium-sensing Receptor Sensitivity', 'Naphthalenes', 'Other Miscellaneous Therapeutic Agents', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB14540,Hydrocortisone butyrate,Hydrocortisone butyrateis a corticosteroid used to treat inflammatory and pruritic corticosteroid-responsive dermatoses.,"['P04083', 'P04150', 'P80365', 'P14060']","Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.",[H][C@@]12CC[C@](OC(=O)CCC)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin- (annexin-) synthesis, which then binds to cell membranes preventing the phospholipase A from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX- and COX-) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin- escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.TargetActionsOrganismAAnnexin ANot AvailableHumansAGlucocorticoid receptorNot AvailableHumansUCorticosteroid -beta-dehydrogenase isozyme Not AvailableHumansU beta-hydroxysteroid dehydrogenase/Delta -->-isomerase type Not AvailableHumans",[],"['11-Hydroxycorticosteroids', '17-Hydroxycorticosteroids', 'Administration, Topical', 'Adrenal Cortex Hormones', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Moderately Potent (Group II)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydrocortisone and derivatives', 'Hydroxycorticosteroids', 'Immunosuppressive Agents', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Steroids']" +DB04552,Niflumic acid,"Niflumic acidis a cyclooxygenase-2 inhibitor used to alleviate inflammation, pain, and edema associated with acute and chronic inflammatory conditions, such as rheumatoid arthritis, osteoarthritis, post-operative inflammatory conditions, and physical trauma.","['P04054', 'P35354', 'P51800', 'P23219', 'P47712', 'O60656']","Niflumic acid, a nonsteroidal anti-inflammatory fenamate, is a Ca2+-activated Cl-channel blocker.",OC(=O)C1=C(NC2=CC=CC(=C2)C(F)(F)F)N=CC=C1,"Niflumic acid is able to inhibit both phospholipase A as well as COX-, thereby acting as an antiinflamatory and pain reduction agent.TargetActionsOrganismAPhospholipase AinhibitorHumansAProstaglandin G/H synthase inhibitorHumansUChloride channel protein ClC-KainducerHumansUProstaglandin G/H synthase Not AvailableHumansUCytosolic phospholipase ANot AvailableHumansUUDP-glucuronosyltransferase -Not AvailableHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Aminobenzoates', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzoates', 'Cyclooxygenase Inhibitors', 'Enzyme Inhibitors', 'Fenamates', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Nicotinic Acids', 'Niflumic Acid and Prodrugs', 'ortho-Aminobenzoates', 'Peripheral Nervous System Agents', 'Pyridines', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain', 'UGT1A9 Inhibitors']" +DB01047,Fluocinonide,Fluocinonideis a high potency corticosteroid commonly used topically for a number of inflammatory skin conditions.,"['P04150', 'Q99835']","Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. It mediates its effects to relieve itching, redness, dryness, crusting, scaling, inflammation, and discomfort associated with inflammatory skin conditions.",[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)COC(C)=O,"Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. Fluocinonide binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin- (annexin-) synthesis, which then binds to cell membranes preventing the phospholipase A from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX- and COX-) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin- escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen). It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUSmoothened homologagonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Allergic Agents', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Pregnadienes', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated', 'Thyroxine-binding globulin inhibitors']" +DB01013,Clobetasol propionate,Clobetasol propionateis a corticosteroid used to treat corticosteroid-responsive dermatoses and plaque psoriasis.,"['P04150', 'P04083', 'P08235']","Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.5Clobetasol propionate is generally applied twice daily so the duration of action is long.10,11,12,13,14,15Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.5Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.5",[H][C@@]12C[C@H](C)[C@](OC(=O)CC)(C(=O)CCl)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-.Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUAnnexin AinducerHumansUMineralocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroids', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated', 'Thyroxine-binding globulin inhibitors']" +DB00288,Amcinonide,Amcinonideis a topical corticosteroid used in the treatment of inflammation and pruritus due to a variety of dermatoses.,"['P04150', 'P04083']","Amcinonide is a topical corticosteroid. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents. Amcinonide reduces or inhibits the actions of chemicals in the body that cause inflammation, redness, and swelling. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. When in an ointment form, amcinonide also helps the skin maintain moisture.",[H][C@@]12C[C@H]3OC4(CCCC4)O[C@@]3(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A. Amcinonide has affinity for the glucocorticoid receptor. It has weak affinity for the progesterone receptor, and virtually no affinity for the mineralocorticoid, estrogen, or androgen receptors.TargetActionsOrganismAGlucocorticoid receptoragonistHumansUAnnexin AagonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Pregnadienes', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated', 'Thyroxine-binding globulin inhibitors']" +DB00880,Chlorothiazide,"Chlorothiazideis a thiazide diuretic used to treat hypertension and edema in congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.","['P55017', 'P00915', 'P00918']","Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl-reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.",NS(=O)(=O)C1=C(Cl)C=C2NC=NS(=O)(=O)C2=C1,"As a diuretic, chlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of chlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.TargetActionsOrganismASolute carrier family member inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumans",[],"['Antihypertensive Agents', 'Benzothiadiazines', 'Cardiovascular Agents', 'Diuretics', 'Drugs causing inadvertant photosensitivity', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Hypotensive Agents', 'Increased Diuresis', 'Membrane Transport Modulators', 'Natriuretic Agents', 'OAT1/SLC22A6 inhibitors', 'Photosensitizing Agents', 'Sodium Chloride Symporter Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB01067,Glipizide,Glipizideis a sulfonylurea medication used in Type 2 Diabetes to sensitize pancreatic beta cells and stimulate insulin release.,"['Q09428', 'P37231']","Glipizide is a blood glucose-lowering agent. The initial onset of blood glucose-lowering effect occurs around 30 minutes post-administration with the duration of action lasting for about 12 to 24 hours.8While the chronic use of glipizide does not result in elevations in the fasting insulin levels over time, the postprandial insulin response, or insulin response to a meal, is observed to be enhanced, even after 6 months of treatment.LabelThe main therapeutic actions of glipizide primarily occur at the pancreas where the insulin release is stimulated, but glipizide also mediates some extrapancreatic effects, such as the promotion of insulin signaling effects on the muscles, fat, or liver cells.9Due to its action on the endogenous cells, sulfonylureas including glipizide is associated with a risk for developing hypoglycemia and weight gain in patients receiving the drug.5,6Chronic administration of glipizide may result in down-regulation of the sulfonylurea receptors on pancreatic beta cells, which are molecular targets of the drug, leading to a reduced effect on insulin secretion.4Like other sulfonylureas, glipizide may work on pancreatic delta (δ) cells and alpha (α) cells to stimulate the secretion of somatostatin and suppress the secretion of glucagon, which are peptide hormones that regulate neuroendocrine and metabolic pathways. Other than its primary action on the pancreas, glipizide also exerts other biological actions outside of the pancreas, or ""extrapancreatic effects"", which is similar to other members of the sulfonylurea drug class. Glipizide may enhance the glucose uptake into the skeletal muscles and potentiate the action of insulin in the liver. Other effects include inhibited lipolysis in the liver and adipose tissue, inhibited hepatic glucose output, and increased uptake and oxidation of glucose. It has also been demonstrated by several studies that the chronic therapeutic use of sulfonylureas may result in an increase in insulin receptors expressed on monocytes, adipocytes, and erythrocytes.4",CC1=NC=C(N=C1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1,"Type diabetes mellitus (TDM) is a chronic metabolic disorder with increasing prevalence worldwide. Characterized by higher-than-normal levels of blood glucose, TDM is a complex disorder that arises from the interaction between genetic, environmental and behavioral risk factors. Insulin is a peptide hormone that plays a critical role in regulating blood glucose levels. In response to high blood glucose levels, insulin promotes the uptake of glucose into the liver, muscle cells, and fat cells for storage. Although there are multiple events occurring that lead to the pathophysiology of TDM, the disorder mainly involves insulin insensitivity as a result of insulin resistance, declining insulin production, and eventual failure of beta cells of pancreatic islets that normally produce insulin.Early management with lifestyle intervention, such as controlled diet and exercise, is critical in reducing the risk of long-term secondary complications, such as cardiovascular mortality.Glipizide, like other sulfonylurea drugs, is an insulin secretagogue, which works by stimulating the insulin release from the pancreatic beta cells thereby increasing the plasma concentrations of insulin.Thus, the main therapeutic action of the drug depends on the functional beta cells in the pancreatic islets.Sulfonylureas bind to the sulfonylurea receptor expressed on the pancreatic beta-cell plasma membrane, leading to the closure of the ATP-sensitive potassium channel and reduced potassium conductance. This results in depolarization of the pancreatic beta cell and opening of the voltage-sensitive calcium channels, promoting calcium ion influx. Increased intracellular concentrations of calcium ions in beta cells stimulates the secretion, or exocytosis, of insulin granules from the cells.Label,Apart from this main mechanism of action, the blood-glucose-lowering effect of glipizide involves increased peripheral glucose utilization via stimulating hepatic gluconeogenesis and by increasing the number and sensitivity of insulin receptors.TargetActionsOrganismAATP-binding cassette sub-family C member inhibitorHumansUPeroxisome proliferator-activated receptor gammaagonistHumans",[],"['Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'Oral Hypoglycemics', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds', 'UGT1A1 Substrates']" +DB00912,Repaglinide,Repaglinideis a antihyperglycemic used to improve glycemic control in diabetes.,"['Q09428', 'P37231', 'P35367']","Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.",CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O,"Repaglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels ( to mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than mmol/L). Repaglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.TargetActionsOrganismAATP-binding cassette sub-family C member inhibitorHumansUPeroxisome proliferator-activated receptor gammaagonistHumansAHistamine H receptorantagonistHumans",[],"['Acids, Acyclic', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Glinide', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'Meglitinides', 'OATP1B1/SLCO1B1 Substrates', 'Oral Hypoglycemics', 'Potassium Channel Blockers', 'Stereoisomerism']" +DB00731,Nateglinide,Nateglinideis a meglitinide used to treat non insulin dependent diabetes mellitus.,"['Q09428', 'P37231']","Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Nateglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.",CC(C)[C@H]1CC[C@@H](CC1)C(=O)N[C@H](CC1=CC=CC=C1)C(O)=O,"Nateglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels ( to mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than mmol/L). Nateglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.TargetActionsOrganismAATP-binding cassette sub-family C member inhibitorHumansUPeroxisome proliferator-activated receptor gammaagonistHumans",[],"['Alimentary Tract and Metabolism', 'Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Blood Glucose Lowering Agents', 'Cyclohexanes', 'Cycloparaffins', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Glinide', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'OAT1/SLC22A6 inhibitors', 'Oral Hypoglycemics', 'Potassium Channel Blockers', 'UGT1A9 Substrates']" +DB09231,Benidipine,Benidipineis a synthetic dihydropyridine calcium channel blocker used to treat hypertension and angina pectoris.,"['Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555', 'Q00975', 'O43497', 'O95180', 'Q9P0X4']","Benidipine reduces systolic and diastolic blood pressure as well as to present decreases in heart rate pulse after treatment. It is reported also a decrease urinary protein excretion and serum triglycerides.4Different studies have shown benidipine anti-oxidative activity, stimulation of NO production, suppression of adhesion molecules expression, stimulation of osteoblast differentiation, suppression of the proliferation of vascular smooth muscle cells and mesangial cells, as well as myocardial protection. The enhancement of NO production is associated with the cardioprotective and antiartheriosclerotic effects of benidipine.2",COC(=O)C1=C(C)NC(C)=C([C@@H]1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)O[C@@H]1CCCN(CC2=CC=CC=C2)C1,"Benidipine is a tripe calcium channel inhibitor by inhibiting L, N and T type calcium channel.It presents a very long-lasting activity that can be explained by its high affinity for cell membranes from the DHP binding site; this characteristic indicated a long-lasting pharmacological activity of benidipine. The additional property of benidipine is the vascular selectivity towards peripheral blood vessels.TargetActionsOrganismAVoltage-dependent L-type calcium channelantagonistHumansAVoltage-dependent N-type calcium channel subunit alpha-BantagonistHumansAVoltage-dependent T-type calcium channelantagonistHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Membrane Transport Modulators', 'Moderate Risk QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB06335,Saxagliptin,Saxagliptinis an DPP-4 inhibitor used for the management of type 2 diabetes mellitus.,['P27487'],"Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong the QTc interval to a clinically significant degree.",[H][C@@]12C[C@]1([H])N([C@@H](C2)C#N)C(=O)[C@@H](N)C12CC3CC(CC(O)(C3)C1)C2,"Saxagliptin is a dipeptidyl peptidase- (DPP-) inhibitor antidiabetic for the treatment of type diabetes. DPP- inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] +DPP- is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP- has two main mechanisms of action, an enzymatic function and another mechanism where DPP- binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S hydroxyl oxygen on DPP-. The inhibition of DPP- increases levels active of glucagon like peptide (GLP-), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.TargetActionsOrganismADipeptidyl peptidase inhibitorHumans",[],"['Agents causing angioedema', 'Alimentary Tract and Metabolism', 'Amino Acids, Peptides, and Proteins', 'Blood Glucose Lowering Agents', 'Bridged-Ring Compounds', 'Cycloparaffins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'DPP-IV Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypoglycemia-Associated Agents', 'Incretins', 'OAT3/SLC22A8 Substrates', 'Oligopeptides', 'Oral Hypoglycemics', 'Peptides', 'Protease Inhibitors']" +DB11827,Ertugliflozin,Ertugliflozinis a SGLT2 inhibitor used to treat type 2 diabetes mellitus.,['P31639'],"Ertugliflozin causes a dose-dependent increase in urinary glucose excretion and an increase in urinary volume in patients with T2DM.3,10",CCOC1=CC=C(CC2=CC(=CC=C2Cl)[C@]23OC[C@](CO)(O2)[C@@H](O)[C@H](O)[C@H]3O)C=C1,"Kidneys play an integral role in glucose homeostasis. After being filtered into urine within the nephron, most of the plasma glucose is reabsorbed through two types of sodium-dependent glucose cotransporters (SGLTs), SGLT and SGLT, expressed in proximal renal tubules.More specifically, SGLT is responsible for –% of renal glucose reabsorption while SGLT is responsible for the remaining -%.Under physiological conditions, less than one percent of glucose is excreted in urine.,In the case of hyperglycemia, SGLTs become saturated and the renal threshold for urinary glucose excretion is increased. Kidneys respond to an elevated threshold for glycosuria by elevating glucose reabsorption and increasing maximum glucose reabsorptive capacity.Ertugliflozin is an inhibitor of SGLT that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.TargetActionsOrganismASodium/glucose cotransporter inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'BCRP/ABCG2 Substrates', 'Blood Glucose Lowering Agents', 'Diuretics', 'Drugs Used in Diabetes', 'P-glycoprotein substrates', 'Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors', 'Sodium-Glucose Transporter 2 Inhibitors', 'UGT1A1 Inhibitors', 'UGT1A4 Inhibitors', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB09089,Trimebutine,Trimebutineis a spasmolytic agent used for the symptomatic treatment of irritable bowel syndrome (IBS) and treatment of postoperative paralytic ileus following abdominal surgery.,"['P35372', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555', 'Q12791', 'Q16558', 'Q9Y691', 'Q9NPA1', 'Q86W47', 'O15554', 'Q92952', 'Q9H2S1', 'Q9UGI6', 'P11229', 'P08172', 'P20309', 'P08173', 'O43497', 'O95180', 'Q9P0X4']","Trimebutine is a spasmolytic agent that acts directly on smooth muscle to modulate gastric motility. It shows a ""dual function"" that stimulates or inhibits spontaneous contractions depending on the concentration and prior contractile activity in the preparation. Targeting ion conductance that regulates GI motility, trimebutine inhibits the inward calcium currents and calcium-dependent potassium currents in a concentration-dependent manner2. At lower concentrations (1-10uM), trimebutine depolarizes the resting membrane potential without affecting the amplitude of contractions, which is thought to be mediated by inhibition of outward potassium currents. It is also shown to activate T-type Ca2+ channel and increase gastric emptying, intestinal and colonic contractility1. At higher concentrations (100-300uM), reduced amplitude of spontaneous contractions and action potentials is thought to be mediated by inhibition of L-type Ca2+ channels and inward calcium current2. Trimebutine mediates a local anesthetic action by acting as a weak agonist at mu opioid receptors.",CCC(COC(=O)C1=CC(OC)=C(OC)C(OC)=C1)(N(C)C)C1=CC=CC=C1,"At high concentrations, trimebutine is shown to inhibit the extracellular Ca+ influx in the smooth muscle cells through voltage dependent L-type Ca+ channels and further Ca+ release from intracellular Ca+ stores,. Trimebutine is suggested to bind to the inactivated state of the calcium channel with high affinity. Reduced calcium influx attenuates membrane depolarization and decrease colon peristalsis. It also inhibits outward K+ currents in response to membrane depolarization of the GI smooth muscle cells at resting conditions through inhibition of delayed rectifier K+ channels and Ca+ dependent K+ channels, which results in induced muscle contractions,. Trimebutine binds to mu opioid receptors with more selectivity compared to delta or kappa opioid receptors but with lower affinity than their natural ligands. Its metabolites (N-monodesmethyl-trimebutine or nor-trimebutine), are also shown to bind to opoid receptors on brain membranes and myenteric synaptosomes.TargetActionsOrganismAMu-type opioid receptoragonistHumansAVoltage-dependent L-type calcium channelinhibitorHumansACalcium-activated potassium channelinhibitorHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansUVoltage-dependent T-type calcium channelactivatorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Antiarrhythmic agents', 'Anticholinergic Agents', 'Antimuscarinics Antispasmodics', 'Autonomic Agents', 'Benzene Derivatives', 'Benzoates', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs for Functional Gastrointestinal Disorders', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Hydroxy Acids', 'Hydroxybenzoate Ethers', 'Hydroxybenzoates', 'Muscarinic Antagonists', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Phenols', 'Phenyl Ethers', 'Potential QTc-Prolonging Agents', 'Prokinetic Agents', 'QTc Prolonging Agents', 'Synthetic Anticholinergics, Esters With Tertiary Amino Group']" +DB01157,Trimetrexate,Trimetrexateis a folate antagonist used for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients as an alternative therapy in combination with leucovorin.,['P00374'],"Trimetrexate, a non-classical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase (DHFR). During DNA synthesis and cellular reproduction, folic acid is reduced to tetrahydrofolic acid by the enzyme folic acid reductase. By interfering with the reduction of folic acid, trimetrexate interferes with tissue cell reproduction. Generally, the most sensitive cells to the antimetabolite effect of trimetrexate are those cells which are most actively proliferating such as malignant cells, dermal epithelium, buccal and intestinal mucosa, bone marrow, fetal cells, and cells of the urinary bladder. Because the proliferation of cells in malignant tissues is greater than in most normal tissues, trimetrexate may impair the growth of the malignant tissues without causing irreversible damage to normal tissues. Due to very serious and potentially life-threatening side-effects of this drug, leucovorin must be co-administered for at least 72 hours after the last dose.",COC1=CC(NCC2=C(C)C3=C(C=C2)N=C(N)N=C3N)=CC(OC)=C1OC,"In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.TargetActionsOrganismADihydrofolate reductaseinhibitorHumans",[],"['Acids, Acyclic', 'Acids, Aldehydic', 'Anti-Infective Agents', 'Antimetabolites', 'Antineoplastic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Carbohydrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Folic Acid Antagonists', 'Hepatotoxic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Hydroxy Acids', 'Narrow Therapeutic Index Drugs', 'Noxae', 'Pharmaceutical Preparations', 'Quinazolines', 'Sugar Acids', 'Toxic Actions', 'Uronic Acids']" +DB09026,Aliskiren,Aliskirenis a direct renin inhibitor used to manage hypertension.,['P00797'],"Aliskiren reduces blood pressure by inhibiting renin. This leads to a cascade of events that decreases blood pressure, lowering the risk of fatal and nonfatal cardiovascular events including stroke and myocardial infarction.2,9",COCCCOC1=C(OC)C=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=C1,"Aliskiren is a renin inhibitor.Renin is secreted by the kidneys when blood volume and renal perfusion decrease. It normally cleaves the protein angiotensinogen to form angiotensin I. Angiotensin I is then converted to angiotensin II, an active protein. Angiotensin II is a potent vasoconstrictor that causes the release of catecholamines into the circulation. It also promotes the secretion of aldosterone in addition to sodium reabsorption, increasing blood pressure. Additionally, angiotensin II acts on the adrenal cortex where it stimulates aldosterone release. Aldosterone increases sodium reabsorption and potassium excretion in the nephron.Aliskiren prevents the above process via binding to renin at its active site, stopping the cleavage of angiotensin, in turn inhibiting the formation of angiotensin I. This ends the cascade of angiotensin II mediated mechanisms that normally increase blood pressure.TargetActionsOrganismARenininhibitorHumans",[],"['Acids, Acyclic', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing hyperkalemia', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Benzene Derivatives', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dicarboxylic Acids', 'Enzyme Inhibitors', 'Ethers', 'Hypotensive Agents', 'Methyl Ethers', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Renin Inhibitors']" +DB00447,Loracarbef,Loracarbef is a carbacephem antibiotic sometimes grouped together with the second-generation cephalosporin antibiotics. It is marketed under the trade name Lorabid.,"['Q75Y35', 'Q8XJ01']","Loracarbef is considered a second generation cephalosporin antibiotic. The advantages of cephalosporin antibiotics include a broad range of activity, a safe record in children with almost no dose-related toxicity, and the lack of need to monitor levels. Adverse reactions are rare and consist primarily of hypersensitivity reactions with urticaria, nonspecific rash, and pruritus. Loracarbef can be used to treat a large number of bacterial infections caused by gram-negative and gram-positive bacteria, including upper respiratory tract bacterial infections, chronic bronchitis, pneumonia, sinusitis, pharyntitis and tonsillitis, skin absceses, urinary tract infections and pyelonephritis caused byE. coli,S. pyogenes,S. aureus,S. saprphyticus,S. penumoniae,H. influenzaeandM. catarrhalis.",N[C@@H](C(=O)N[C@H]1[C@H]2CCC(Cl)=C(N2C1=O)C(O)=O)C1=CC=CC=C1,"Loracarbef is an oral, synthetic beta-lactam antibiotic of the carbacephem class. Chemically, carbacephems differ from cephalosporin-class antibiotics in the dihydrothiazine ring where a methylene group has been substituted for a sulfur atom. Loracarbef has a spectrum of activity similar to that of the second generation cephalosporins. It is structurally identical to cefaclor except for a sulfur atom that has been replaced by a methylene group. This change gives greater chemical stability in solution and allows storage at room temperature. Loracarbef, like all b-lactams and cephalosporins, inhibits penicillin binding proteins, enzymes that create the cross-linkage of the peptidoglycan polymer. This binding leads to interference with the formation and remodeling of the cell wall structure.TargetActionsOrganismAPenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB06448,Lonafarnib,Lonafarnibis a potent farnesyl transferase inhibitor used to reduce mortality associated with Hutchinson-Gilford progeria syndrome (HGPS) and other progeroid laminopathies.,"['P49354', 'P49356']","Lonafarnib is a direct farnesyl transferase inhibitor that reduces the farnesylation of numerous cellular proteins, including progerin, the aberrantly truncated form of lamin A that accumulates in progeroid laminopathies such as Hutchinson-Gilford progeria syndrome. Treatment with lonafarnib has been associated with electrolyte abnormalities, myelosuppression, and increased liver enzyme levels (AST/ALT), although causation remains unclear. Also, lonafarnib is known to cause nephrotoxicity in rats and rod-dependent low-light vision decline in monkeys at plasma levels similar to those achieved under recommended dosing guidelines in humans; patients taking lonafarnib should undergo regular monitoring for both renal and ophthalmological function. In addition, based on observations from animal studies with rats, monkeys, and rabbits with plasma drug concentrations approximately equal to those attained in humans, lonafarnib may cause both male and female fertility impairment and embryo-fetal toxicity.13",NC(=O)N1CCC(CC(=O)N2CCC(CC2)[C@H]2C3=C(CCC4=C2C(Br)=CC(Cl)=C4)C=C(Br)C=N3)CC1,"Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder estimated to affect approximately one in million individuals resulting in premature ageing, associated cardiovascular, cerebrovascular, and musculoskeletal effects and early death around years of age.,,,TheLMNAgene encodes lamin A and lamin C, two proteins involved in nuclear integrity and function at the inner nuclear membrane. Under normal conditions, the -exonLMNAgene produces full-length prelamin A, which undergoes farnesylation of the C-terminalCaaXmotif, followed by proteolytic cleavage of the terminal three amino acids (aaX) by the metalloproteinase ZMPSTE, subsequent carboxymethylation, and finally removal of the last amino acids to yield mature, unfarnesylated, lamin A protein.,In HGPS, a single heterozygous C-to-T mutation at position results in a cryptic splice site that removes the last nucleotides of exon and a concomitant -amino acid deletion in the C-terminus of the prelamin A protein. This aberrant prelamin A protein, often called progerin, is permanently farnesylated but unable to complete maturation due to the removal of the second endoproteolytic cleavage site.,Although the exact mechanism is unclear, progerin accumulation results in a host of adverse symptoms associated with ageing such as skeletal dysplasia, joint contractures, atherosclerosis, myocardial fibrosis/dysfunction, scleroderma-like cutaneous effects, lipoatrophy, alopecia, and a severe failure to thrive.,,,,An additional notable effect of HGPS is increased vascular and peripheral calcification.Children affected by HGPS typically die due to myocardial infarction or stroke.Mechanistic understanding of HGPS remains unclear, although a recent study correlated progerin accumulation, telomere dysfunction, DNA damage-mediated inflammatory cytokine release, and HGPS symptoms, suggesting that the nuclear effects of progerin accumulation may result in pleiotropic downstream effects.Lonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), with a reported ICvalue of . nM; lonafarnib is specific for FTase, as it does not appreciably inhibit the related GGPT- enzyme at concentrations up to μM.Inhibition of progerin farnesylation reduces progerin accumulation in the inner nuclear membrane, which subsequently slows the progression of HGPS and other progeroid laminopathies.,,,TargetActionsOrganismAProtein farnesyltransferase/geranylgeranyltransferase type- subunit alphainhibitorHumansAProtein farnesyltransferase subunit betainhibitorHumans",[],"['Alimentary Tract and Metabolism', 'BCRP/ABCG2 Inhibitors', 'Benzocycloheptenes', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strong)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Farnesyltransferase Inhibitor', 'Farnesyltransferase Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B3 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Various Alimentary Tract and Metabolism Products']" +DB12598,Nafamostat,Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.,"['P00734', 'P00742', 'P00748', 'P07477', 'P06870', 'P05362']",Nafamostat is a fast-acting proteolytic inhibitor used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin by competitively inhibiting several serine proteases including thrombin. It improves acute pancreatitis and prevents blood clot formation during extracorporeal circulation and has an anti-inflammatory effect in vitro. A study suggets that nafamostat has a neuroprotective role during ischemia-induced brain injury from antithrombin activity5.,NC(=N)NC1=CC=C(C=C1)C(=O)OC1=CC2=C(C=C1)C=C(C=C2)C(N)=N,"Nafamostat mesilate inhibits various enzyme systems, such as coagulation and fibrinolytic systems (thrombin, Xa, and XIIa), the kallikrein–kinin system, the complement system, pancreatic proteases and activation of protease-activated receptors (PARs). Nafamostat inhibits lipopolysaccharide-induced nitric oxide production, apoptosis, and interleukin (IL)- and IL- levels in cultured human trophoblasts. It is shown to act as an antioxidant in TNF-α-induced ROS production.TargetActionsOrganismAProthrombininhibitorHumansACoagulation factor XinhibitorHumansACoagulation factor XIIinhibitorHumansATrypsin-inhibitorHumansAKallikrein-inhibitorHumansUIntercellular adhesion molecule inhibitorHumans",[],"['Amidines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anticoagulants', 'Antirheumatic Agents', 'Complement Inactivating Agents', 'Enzyme Inhibitors', 'Fibrinolysin, antagonists & inhibitors', 'Hematologic Agents', 'Immunologic Factors', 'Kallikreins, antagonists & inhibitors', 'OCT1 substrates', 'OCT2 Substrates', 'Peripheral Nervous System Agents', 'Protease Inhibitors', 'Sensory System Agents', 'Serine Protease Inhibitors', 'Trypsin Inhibitors']" +DB00528,Lercanidipine,Lercanidipineis a calcium channel blocker for the management of hypertension.,['Q06432'],"Lercanidipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Lercanidipine is similar to other peripheral vasodilators. Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.",COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)(C)CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=C1,"By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Lercanidipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.TargetActionsOrganismAVoltage-dependent calcium channel gamma- subunitinhibitorHumans",[],"['ACE Inhibitors and Calcium Channel Blockers', 'Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Pyridines', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00919,Spectinomycin,Spectinomycinis an aminocyclitol antibiotic used to treat susceptible strains of Neisseria gonorrhoeae.,['P0A7S3'],Spectinomycin is an aminocyclitol antibiotic produced by a species of soil microorganism designated as Streptomyces spectabilis. In vitro studies have shown spectinomycin to be active against most strains ofNeisseria gonorrhoeae(minimum inhibitory concentration <7.5 to 20 mcg/mL). Footprint studies indicate that spectinomycin exerts regional effects on ribosomal structure.,[H][C@@]12O[C@H](C)CC(=O)[C@]1(O)O[C@]1([H])[C@@H](NC)[C@@H](O)[C@@H](NC)[C@H](O)[C@@]1([H])O2,Spectinomycin is an inhibitor of protein synthesis in the bacterial cell; the site of action is the S ribosomal subunit. It is bactericidal in its action.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K),[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Carbohydrates', 'Dioxanes', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring']" +DB01148,Flavoxate,"Flavoxateis a muscarinic antagonist and spasmolytic used for the symptomatic relief of conditions associated with lack of muscle control in the bladder, such as dysuria, urgency, and nocturia.","['P11229', 'P08172']","Flavoxate is a spasmolytic flavone derivative that acts by relaxing the smooth muscle in the urinary tract. Flavoxate is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Muscarinic receptors play an important role in several major cholin-ergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.",CC1=C(OC2=C(C=CC=C2C(=O)OCCN2CCCCC2)C1=O)C1=CC=CC=C1,"Flavoxate acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, urge severity and improving retention, facilitating increased volume per void.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anticholinergic Agents', 'Autonomic Agents', 'Benzopyrans', 'Chromones', 'Drugs for Urinary Frequency and Incontinence', 'Drugs that are Mainly Renally Excreted', 'Flavones', 'Flavonoids', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Pyrans', 'Urological Agents', 'Urologicals']" +DB01150,Cefprozil,"Cefprozilis a cephalosporin antibiotic used in the treatment of various bacterial infections, such as pharyngitis, tonsillitis, otitis media, and uncomplicated skin infections.","['Q04707', 'P14677', 'P0A3M5']","Cefprozil, a semisynthetic, second-generation cephalosporin, is used to treat otitis media, soft-tissue infections, and respiratory tract infections.",[H][C@]12SCC(C=CC)=C(N1C(=O)[C@@]2([H])NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O,"Cefprozil, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefprozil interferes with an autolysin inhibitor.TargetActionsOrganismAPenicillin-binding protein AinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)APenicillin-binding protein xinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)APenicillin-binding protein BinhibitorStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta Lactam Antibiotics', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Second-Generation Cephalosporins', 'Sulfur Compounds', 'Thiazines']" +DB00364,Sucralfate,Sucralfateis a gastro-duodenal protective agent used in the treatment of gastric and duodenal ulcers and to prevent duodenal ulcer recurrence.,"['P0DJD9', 'P09038', 'P01133']","This drug aids in the healing of duodenal ulcers, relieving painful inflammation by creating a protective mechanical barrier between the lining or skin of the gastrointestinal tract and damaging substances2. In addition, sucralfate acts to increase levels of growth factors locally, and also causes an increase in prostaglandins which are important in the healing of the mucosa (lining) of the gastrointestinal tract2.",O.O[Al](O)O.O[Al](O)OS(=O)(=O)OC[C@H]1O[C@@](COS(=O)(=O)O[Al](O)O)(O[C@H]2O[C@H](COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@H]2OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]1OS(=O)(=O)O[Al](O)O,"The mechanism of action of this drug in the healing duodenal ulcers is not yet completely defined, however, there are several probable mechanisms that adequately describe the healing activity of sucralfate. There is evidence that sucralfate acts locally to aid in tissue healing, and not systemicallyLabel.Studies in both humans and animals have indicated that sucralfate forms a complex that binds to protein-rich exudate found on the surface of ulcers. It binds to albumin and fibrinogen,preventing blood clot lysis by stomach acid (hydrochloric acid). Sucralfate increases the tissue levels of fibroblast growth factors and epidermal growth factors,,leading to an increase in prostaglandins at the gastrointestinal tract lining, which promotes the healing of gastrointestinal ulcers.In the laboratory setting, a sucralfate-albumin film provides a barrier against the entry of hydrogen ions, which are a component of gastric acid. In humans, sucralfate, given at therapeutic doses for ulcers, decreases pepsin activity in gastric fluids by %Label. Pepsin has been shown to be damaging to tissues, further aggravating ulcer lesion inflammation. Bile salts have been implicated in mucosal injury to the gastrointestinal tract,. Sucralfate has also been shown to adsorb bile salts in the laboratory, setting, which could further contribute to its beneficial effects in ulcer healingLabel.TargetActionsOrganismAPepsin A-inhibitorHumansAFibroblast growth factor agonistinducerHumansAPro-epidermal growth factorinducerHumansUFibrinogenbinderHumans",['Anti-platelet Therapy'],"['Alimentary Tract and Metabolism', 'Aluminium Compounds', 'Aluminum Complex', 'Anti-Ulcer Agents', 'Carbohydrates', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Drugs that are Mainly Renally Excreted', 'Gastric Cytoprotectants', 'Gastrointestinal Agents', 'Glycosides', 'Metal cations', 'Metal divalent cations', 'Organometallic Compounds', 'Protectants', 'Sulfur Compounds', 'Thioglycosides']" +DB00835,Brompheniramine,"Brompheniramineis a histamine H1 antagonist used to treat coughs, upper respiratory symptoms, and nasal congestion associated with allergies and the common cold.","['P35367', 'P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Brompheniramine is an antihistaminergic medication of the propylamine class. It is a first-generation antihistamine. In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Brompheniramine is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",CN(C)CCC(C1=CC=C(Br)C=C1)C1=CC=CC=N1,"Brompheniramine is an antagonist of the H histamine receptors with moderate antimuscarinic actions, as with other common antihistamines such as diphenhydramine. Due to its anticholindergic effects, brompheniramine may cause drowsiness, sedation, dry mouth, dry throat, blurred vision, and increased heart rate.TargetActionsOrganismAHistamine H receptorantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",['Airway secretion clearance therapy'],"['Agents producing tachycardia', 'Anti-Allergic Agents', 'Anticholinergic Agents', 'Antihistamines for Systemic Use', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 Substrates', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'Propylamine Derivatives', 'Pyridines', 'QTc Prolonging Agents', 'Substituted Alkylamines']" +DB04982,Talampanel,"Talampanel is a substance that is being studied in the treatment of brain tumors and other brain disorders, such as epilepsy and Parkinson disease. It is a type of AMPA receptor antagonist.","['P42261', 'P42262', 'P42263', 'P48058']","Talampanel, a potent and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor antagonist, is a potential new antiepileptic drug (AED). Talampanel dosing strategies may be reliant on concomitant AED medication, as enzyme-inducing AEDs enhance, whereas VPA inhibits its metabolism. Talampanel was well tolerated, although adverse events occurred at lower doses compared with those in healthy subjects, probably because of the additive effect of concomitant AEDs.",C[C@@H]1CC2=CC3=C(OCO3)C=C2C(=NN1C(C)=O)C1=CC=C(N)C=C1,"Talampanel is a potent noncompetitive and selective antagonist of the glutamine AMPA receptors. Studies in primates have shown that the administration of talampanel to parkinsonian monkeys significantly decreased levodopa-induced dyskinesias by %. When given alone, talampanel did not modify the severity of parkinsonian symptoms. However, in combination with levodopa, talampanel potentiated the antiparkinsonian action of levodopa by increasing motor activity.TargetActionsOrganismUGlutamate receptor Not AvailableHumansUGlutamate receptor Not AvailableHumansUGlutamate receptor Not AvailableHumansUGlutamate receptor Not AvailableHumans",[],"['Benzazepines', 'Heterocyclic Compounds, Fused-Ring', 'Receptors, AMPA, antagonists & inhibitors']" +DB00486,Nabilone,Nabiloneis a synthetic delta-9-THC used in the treatment of anorexia and weight loss in HIV patients as well as nausea and vomiting in cancer chemotherapy.,"['P34972', 'P21554']","Nabilone is a cannabinoid with therapeutic uses. It is an analog of dronabinol (also known as tetrahydrocannabinol or THC), the psychoactive ingredient in cannabis. Although structurally distinct from THC, nabilone mimics THC's structure and pharmacological activity through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, however it is considered to be twice as active as Δ⁹-THC.",[H][C@@]12CC(=O)CC[C@@]1([H])C(C)(C)OC1=CC(=CC(O)=C21)C(C)(C)CCCCCC,"Nabilone is an orally active synthetic cannabinoid which, like other cannabinoids, has complex effects on the central nervous system (CNS). It has been suggested that the antiemetic effect of nabilone is caused by interaction with the cannabinoid receptor system, i.e., the CB () receptor, which is a component of the endocannabinoid system of the body.The endocannabinoid system is widely distributed throughout the central and peripheral nervous system (via the Cannabinoid Receptors CB and CB) and plays a role in many physiological processes such as inflammation, cardiovascular function, learning, pain, memory, stress and emotional regulation, and the sleep/wake cycle among many others. CB receptors are found in both the central and peripheral nervous system, and are most abundant in the hippocampus and amygdala, which are the areas of the brain responsible for short-term memory storage and emotional regulation. CB receptors are mainly located in the peripheral nervous system and can be found on lymphoid tissue where they are involved in regulation of immune function.TargetActionsOrganismACannabinoid receptor partial agonistHumansACannabinoid receptor partial agonistHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Antiemetics', 'Antiemetics and Antinauseants', 'Autonomic Agents', 'Cannabinoids and similars', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Gastrointestinal Agents', 'Hypotensive Agents', 'Miscellaneous Antiemetics', 'Peripheral Nervous System Agents', 'Photosensitizing Agents', 'Psychotropic Drugs', 'Terpenes', 'Tranquilizing Agents']" +DB01283,Lumiracoxib,"Lumiracoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID). On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure. New Zealand and Canada have also followed suit in recalling the drug.","['P35354', 'P23219']","Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity.",CC1=CC=C(NC2=C(Cl)C=CC=C2F)C(CC(O)=O)=C1,The mechanism of action of lumiracoxib is due to inhibition of prostaglandin synthesis via inhibition of cyclooygenase- (COX-). Lumiracoxib does not inhibit COX- at therapeutic concentrations.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans,[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'COX-2 Inhibitors', 'Cyclooxygenase Inhibitors', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Peripheral Nervous System Agents', 'Phenylacetates', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory System Agents', 'UGT1A9 Substrates']" +DB00751,Epinastine,Epinastineis an H1 receptor antagonist used to prevent itching in allergic conjunctivitis.,"['P35367', 'P25021', 'P35348', 'P08913', 'P28223', 'P34969']","Epinastine is an antihistamine and an inhibitor of histamine release from the mast cell for topical administration to the eyes. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. Epinastine is a topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H1-receptor and has affinity for the histamine H2 receptor. Epinastine also possesses affinity for the a1-, a2-, and 5-HT2-receptors. Epinastine does not penetrate the blood/brain barrier and, therefore, is not expected to induce side effects of the central nervous system.",NC1=NCC2N1C1=CC=CC=C1CC1=CC=CC=C21,"Epinastine has a multiaction effect that inhibits the allergic response in ways: . stabilizes mast cells by preventing mast cell degranulation to control the allergic response, . prevents histamine binding to both the H- and H-receptors to stop itching and provide lasting protection, and . prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response.TargetActionsOrganismAHistamine H receptorantagonistHumansAHistamine H receptorantagonistHumansUAlpha-A adrenergic receptorunknownHumansUAlpha-A adrenergic receptorunknownHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor antagonistHumans",[],"['Acid Reducers', 'Antidepressive Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decongestants and Antiallergics', 'Decreased Histamine Release', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Inhibitors', 'Histamine H2 Antagonists', 'Neurotransmitter Agents', 'Ophthalmics', 'Ophthalmologicals', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sensory Organs', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB09224,Melperone,"Melperoneis an atypical butyrophenone antipsychotic used to treat sleep disorders, confusion, and psychomotor dysfunction associated with geriatric, psychiatric, and alcohol-dependent patients.",['P14416'],"Melperone has been demonstrated to produce an antipsychotic effect at doses that cause minimal extrapyramidal symptoms frequently associated with more traditional antipsychotics6,8.",CC1CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1,"Melperone demonstrates antagonist activity at D dopaminergic and HTA serotonergic receptors. It has a weak affinity to D receptors and possesses less risk of inducing dopamine receptor supersensitivity after both acute and chronic administration. In addition, the ratio of dopamine D/D occupancy for melperone has been shown to resemble the binding profile of clozapine.TargetActionsOrganismADopamine D receptorantagonistHumans",[],"['Antiarrhythmic agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Butyrophenone Derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Ketones', 'Moderate Risk QTc-Prolonging Agents', 'Nervous System', 'Neurotoxic agents', 'Psycholeptics', 'Psychotropic Drugs', 'QTc Prolonging Agents', 'Tranquilizing Agents']" +DB09227,Barnidipine,Barnidipineis a calcium channel blocker used to treat various forms of hypertension.,"['Q13936', 'O43497', 'O95180']","Barnidipine reduces peripheral resistance and lowers blood pressure. The chronic use of the drug is not reported to lead to an increase in basic heart frequency. The antihypertensive effects of barnidipine are reported to remain during the entire 24-hour dose interval. Barnidipine does not exert any negative effect on serum lipids profile, glucose level or blood electrolytes8.",COC(=O)C1=C(C)NC(C)=C([C@H]1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)O[C@H]1CCN(CC2=CC=CC=C2)C1,"Barnidipine is a lipophilic ,-dihydropyridine calcium antagonist that is characterized by a slow onset of action and a strong and long-lasting binding to the L-type calcium channels. It displays high affinity for the channels expressed in the smooth muscle cells in the vascular wall. Its main mechanism of action arises from the reduction of peripheral vascular resistance secondary to its vasodilatory actions.Calcium ion influx via L-subtype ‘voltage-operated’ channels in the excitable membranes of the smooth muscle cells promotes the formation of calcium-dependent formation of cross-bridges between myosin and actin which are the two major contractile proteins that drive contraction. By blocking the L-type 'voltage-dependent' calcium channels, barnidipine selectively blocks the calcium ion influx in the smooth muscle cells and inhibits the activation of contractile proteins. It is suggested that barnidipine displays a high affinity to the inactivated state of the channel. Like other dihydropyridine calcium antagonists, barnidipine is predicted to interact with the alpha -C subunit of the L-type calcium channels. Alpha -C subunit of the channel is predicted to reside within the bilayer or channel pore at a location closer to the extracellular rather than the intracellular face of the membrane,. Its lipophilicity is likely a reason why barnidipine displays a slow onset and long duration of action. Being a highly lipophilic molecule with an octanol/water partition coefficient of , barnidipine is expected to accumulate in the cell membrane and consequently, gains access to its target receptor in a slow manner.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CantagonistHumansUVoltage-dependent T-type calcium channel subunit alpha-GantagonistinhibitorHumansUVoltage-dependent T-type calcium channel subunit alpha-HantagonistinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Pyridines', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB05511,Piclidenoson,"CF 101 (known generically as IB-MECA) is an anti-inflammatory drug for rheumatoid arthritis patients. Its novel mechanism of action relies on antagonism of adenoside A3 receptors. +CF101 is supplied as an oral drug and has an excellent safety profile. It is also being considered for the treatment of other autoimmune-inflammatory disorders, such as Crohn's disease, psorasis and dry eye syndrome.",['P0DMS8'],"CF-101 is an adenoside A3 agonist for the treatment of a variety of autoimmune-inflammatory disorders, particularly rhematoid arthritis. In clinical trials, it was found to be safe, well tolerated and showed strong evidence of an anti-inflammatory effect in rheumatoid arthritis patients. In this trial, a statistically significant correlation was found between A(3)AR expression level and response to the drug, so A(3)AR expression may serve as a biopredictor of patient response.",CNC(=O)[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C(NCC3=CC(I)=CC=C3)N=CN=C12,"CF is an A()AR agonist. A()AR is highly expressed in inflammatory cells and overexpressed in peripheral blood mononuclear cells, reflecting its role in the remote inflammatory process. In normal tissues, there is low adenoside A receptor expression. A()AR activation with a specific agonist deregulates the NF-kappaB signaling pathway in inflammatory cells and initiates immunomodulatory effects.TargetActionsOrganismUAdenosine receptor ANot AvailableHumans",[],"['Heterocyclic Compounds, Fused-Ring', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Purine Nucleosides', 'Purines', 'Ribonucleosides']" +DB04879,Vatalanib,Vatalanib (PTK787/ZK-222584) is a new oral antiangiogenic molecule that inhibits all known vascular endothelial growth factor receptors. Vatalanib is under investigation for the treatment of solid tumors.,"['P17948', 'P35968', 'P35916']","Vatalanib is a novel oral angiogenesis inhibitor being developed by Schering (in collaboration with Novartis AG). Vatalanib selectively inhibits the tyrosine kinase domains of vascular endothelial growth factor (VEGF) receptors, platelet-derived growth factor (PDGF) receptor, and c-KIT.",ClC1=CC=C(NC2=NN=C(CC3=CC=NC=C3)C3=CC=CC=C23)C=C1,"Vatalanib potently inhibits vascular endothelial growth factor (VEGF) receptor tyrosine kinases, important enzymes in the formation of new blood vessels that contribute to tumor growth and metastasis.TargetActionsOrganismUVascular endothelial growth factor receptor Not AvailableHumansUVascular endothelial growth factor receptor Not AvailableHumansUVascular endothelial growth factor receptor Not AvailableHumans",[],"['Enzyme Inhibitors', 'Protein Kinase Inhibitors', 'Pyridazines', 'Tyrosine Kinase Inhibitors']" +DB06212,Tolvaptan,Tolvaptanis a selective vasopressin V2-receptor antagonist to slow kidney function decline in patients at risk for rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). Also used to treat hypervolemic and euvolemic hyponatremia.,"['P30518', 'P37288']","Urine volume and fluid intake increase in a dose dependent manner which results in overall negative fluid balance in patients taking tolvaptan. Increases in serum sodium and osmolality can be observed 4-8 hours post-administration and is maintained for 24 hours. The magnitude of serum sodium and osmolality change increases with escalating doses. Furthermore, a decrease in urine osmolality and increase in free water clearance can be observed 4 hours after post-administration of tolvaptan. The affinity for V2 receptors is 29x greater than that of V1a receptors and does not have any appreciable affinity for V2 receptors.",CC1=CC=CC=C1C(=O)NC1=CC(C)=C(C=C1)C(=O)N1CCC[C@@H](O)C2=C1C=CC(Cl)=C2,"Tolvaptan is a selective and competitive arginine vasopressin receptor antagonist. Vasopressin acts on the V receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin.TargetActionsOrganismAVasopressin V receptorantagonistHumansNVasopressin Va receptorantagonistHumans",[],"['Agents causing hyperkalemia', 'Antidiuretic Hormone Receptor Antagonists', 'Benzazepines', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Diuretics', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Natriuretic Agents', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Vasopressin V2 Receptor Antagonist', 'Vasopressin V2 Receptor Antagonists']" +DB11195,Xylitol,Xylitolis an ingredient added to dental products to remove bacteria.,"['P12070', 'P24300', 'P15587', 'P12851', 'Q54873']","There has been evidence of xylitol in dental hygiene in reducing dental caries disease and also reversing the process of early caries1. Xylitol increases salivary flow and pH, reduces the levels ofStreptococcus mutansin plaque and saliva and reduces the adhesion on the microorganism to the teeth surface1.Streptococcus mutansis the main target plaque microorganism2, but xylitol may potentially have inhibitory actions against several other bacterial species1. +It prevents a shift of the bacterial community towards a more cariogenic microflora in oral environment4. Oral ingestion of xylitol causes a smaller rise in plasma glucose and insulin concentrations than does the ingestion of glucose in healthy men and diabetics6.",OC[C@H](O)[C@@H](O)[C@H](O)CO,"Xylitol is initially taken up by the microorganism and accumulates intracellularly. Accumulated xylitol is transported into an energy-consuming cycle, or the inducible fructose transport system. It is converted to non-metabolizable, toxic xylitol--phosphate via phosphoenolpyruvate: a constitutive fructose phosphotransferase system byS. mutans. This metabolic process of xylitol, without the gain of any energy molecules, results in the development of intracellular vacuoles and cell membrane degradation.S. mutansdephosphorylates xylitol--phosphate and expels it from the cell, in which requires energy consumption. This ultimately leading to starving of microorganism and growth inhibition. Long-term exposure to xylitol can cause microorganisms to develop resistance to xylitol. This clinically beneficial selection process creates xylitol-resistant mutans strains that are less virulent and less cariogenic than their parent strains. Xylitol also increases the concentrations of ammonia and amino acids in plaque, thereby neutralizing plaque acids. A study suggests that xylitol may also promote remineralization of deeper layers of demineralized enamel by facilitating Ca+ and phosphate movement and accessibility.TargetActionsOrganismUXylose isomeraseNot AvailableArthrobacter sp. (strain NRRL B)UXylose isomeraseNot AvailableStreptomyces rubiginosusUXylose isomeraseNot AvailableStreptomyces olivochromogenesUXylose isomeraseNot AvailableActinoplanes missouriensis (strain ATCC / DSM / CBS . / JCM / NCIMB / NBRC / )UHyaluronate lyaseNot AvailableStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)",[],"['Alcohols', 'Carbohydrates', 'Compounds used in a research, industrial, or household setting', 'Diet, Food, and Nutrition', 'Flavoring Agents', 'Food', 'Food Additives', 'Food Ingredients', 'Physiological Phenomena', 'Sugar Alcohols', 'Sweetening Agents']" +DB04573,Estriol,"Estriolis a weak estrogen used to treat vaginal dryness and estrogen deficiency conditions, such as vaginitis and vulvar itching.","['P03372', 'Q92731', 'P04278']","Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.",[H][C@@]12C[C@@H](O)[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3,"Estriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta. If levels of ""unconjugated estriol"" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. The drug interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estriol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.TargetActionsOrganismAEstrogen receptor alphaagonistHumansUEstrogen receptor betaagonistHumansUSex hormone-binding globulinNot AvailableHumans",['Estrogen Replacement Therapy'],"['Estradiol Congeners', 'Estranes', 'Estrenes', 'Estrogens', 'Fused-Ring Compounds', 'Genito Urinary System and Sex Hormones', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Natural and Semisynthetic Estrogens, Plain', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Sex Hormones and Modulators of the Genital System', 'Steroids', 'Thyroxine-binding globulin inducers']" +DB11979,Elagolix,Elagolixis a gonadotropin releasing hormone receptor antagonist used to treat moderate to severe pain in endometriosis.,['P30968'],"During a three menstrual cycle study in healthy women, an elagolix 150 mg once daily regimen and a 200 mg twice daily regimen resulted in an ovulation rate of about 50% and 32%, respectivelyLabel. In Phase 3 trials in women with endometriosis, elagolix caused a dose-dependent reduction in median estradiol concentrations to approximately 42 pg/mL for the 150 mg once daily regimen and 12 pg/mL for the 200 mg twice daily regimenLabel.Furthermore, the effect of elagolix on the QTc interval was investigated in a randomized, placebo- and positive-controlled, open-label, single-dose, crossover thorough QTc study in 48 healthy adult premenopausal womenLabel. Elagolix concentrations in subjects administered a single dose of 1200 mg was seventeen times higher than the concentration in subjects given elagolix 200 mg twice daily. Nevertheless, there was no clinically relevant prolongation of the QTc intervalLabel.",COC1=CC=CC(=C1F)C1=C(C)N(CC2=C(C=CC=C2F)C(F)(F)F)C(=O)N(C[C@H](NCCCC(O)=O)C2=CC=CC=C2)C1=O,"Endometriosis develops when tissue that is similar to the kind that is normally located in the uterus starts to grow outside of the uterus,. Such growth leads to various symptoms like pain during periods, pelvic pain between periods, and pain during sexual intercourse,. The growths themselves are referred to as lesions and frequently develop on the ovaries, fallopian tubes, and other areas around the uterus, including the bowel or bladder,. The growth of these lesions is dependent upon the estrogen hormone.Elagolix is an orally-administered, nonpeptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary glandLabel,,,. Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.TargetActionsOrganismUGonadotropin-releasing hormone receptorantagonistHumans",[],"['Anti-Gonadotropin-Releasing Hormones', 'Antigonadotropins and Similar Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased GnRH Secretion', 'Gonadotropin Releasing Hormone Receptor Antagonists', 'Gonadotropin-releasing Hormone Antagonists', 'Hydrocarbons, Halogenated', 'Hypothalamic Hormones', 'OATP1B1/SLCO1B1 Substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Pituitary and Hypothalamic Hormones and Analogues', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'UGT1A1 Substrates']" +DB05885,Seletracetam,"Seletracetam is a pyrrolidone derivative and with a structural similarity to newer generation antiepileptic drug levetiracetam. It binds to the same target as levetiracetam but with higher affinity and has shown potent seizure suppression in models of acquired and genetic epilepsy with high CNS tolerability. It is predicted to have low drug-drug interactions and inhibition or induction of any major human metabolizing enzymes. Seletracetam was in Phase II clinical trials under the supervision of the U.S. Food and Drug Administration (FDA) investigated as treatment of epilepsy and partial epilepsy however its development had been put on hold in July 2007. As of 2010, its production was further halted due to the investigation of a newer antiepileptic agent, brivaracetam.","['Q7L0J3', 'Q00975', 'P23415', 'P48167']",Seletracetam is an antiepileptic agent that targets the presynaptic mechanisms of epilepsy. It interferes with synaptic vesicle exocytosis and neurotransmitter release by binding to synaptic vesicle protein 2A (SV2A) which is involved in synaptic vesicle docking and fusion. It is also a N-type calcium channel blocker that inhibits the abnormal neuronal discharge by inhibiting the calcium channel function and associated calcium currents. Seletracetam markedly reduces epileptiform markers of both hyper-excitability and hyper-synchronization in an in vitro slice model of epilepsy and potently suppresses seizures in in vivo epilepsy models mimicking both partial and generalized epilepsy7.,CC[C@H](N1C[C@@H](CC1=O)C=C(F)F)C(N)=O,"Seletracetam binds to SVA in a stereospecific and selective manner. SVA is a membrane glycoprotein present in synaptic vesicles of neurons that plays a role as calcium regulators in neurotransmitter release and modulate synaptic networks. Seletracetam is thought to reduce excessive neuronal activity by modulating SVA function and restoring the ability of a neuron to regulate its neurotransmitter release. +Seizure generation induces a sustained membrane depolarization causing a prolonged firing of voltage-dependent calcium currents sufficient to induce a significant rise in calcium concentration. High voltage-activated calcium currents are inhibited by seletracetam by blocking N-type calcium channels in the pyramidal neurons. The drug reduces the degree of calcium influx and decreases the intraneuronal calcium concentration, blocking the abnormal fluctuations in membrane potential occurring during epileptic discharges.TargetActionsOrganismASynaptic vesicle glycoprotein AmodulatorHumansAVoltage-dependent N-type calcium channel subunit alpha-BblockerHumansUGlycine receptor (alpha-/beta)bindingHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Pyrrolidines', 'Vasodilating Agents']" +DB05541,Brivaracetam,Brivaracetamis an anticonvulsant used for the treatment of partial-onset seizures that functions by binding to synaptic vesicle glycoprotein 2A (SV2A) in the brain.,"['Q7L0J3', 'P35498', 'Q9Y5Y9', 'Q9UI33', 'Q99250', 'Q9NY46', 'P35499', 'Q14524', 'Q01118', 'Q9UQD0', 'Q15858', 'Q07699', 'O60939', 'Q9NY72', 'Q8IWT1']",Brivaracetam binds SV2A with high affinity2. SV2A is known to play a role in epileptogenesis through modulation of synaptic GABA release3. It is thought that brivaracetam exerts its anti-epileptogenic effects through its binding to SV2A. Brivaracetam is also known to inhibit Na+ channels which may also contribute to its anti-epileptogenic action4.,CCC[C@H]1CN([C@@H](CC)C(N)=O)C(=O)C1,The precise mechanism of brivaracetam's anti-epileptogenic activity is unknown.TargetActionsOrganismASynaptic vesicle glycoprotein AunknownHumansASodium channel proteininhibitorHumans,[],"['Anticonvulsants', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Epoxide Hydrolase Inhibitors', 'Miscellaneous Anticonvulsants', 'Nervous System', 'Pyrrolidines']" +DB01320,Fosphenytoin,Fosphenytoinis an antiepileptic agent used for the management of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery.,['Q14524'],"Fosphenytoin is a water-soluble phenytoin prodrug used for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. Each 1.5 mg of fosphenytoin sodium is equivalent to 1.0mg of phenytoin sodium (PE equivalents); care should be taken to calculate the dose required in PE equivalents properly. Serious adverse effects such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), and hematopoietic complications may occur and indicate an alternate antiepileptic should be used. Withdrawal of fosphenytoin sodium may precipitate seizures and should be done gradually.6",OP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1,"Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",[],"['Anti-epileptic Agent', 'Anticonvulsants', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Enzyme Inducing Antiepileptic Drugs', 'Hydantoins', 'Imidazoles', 'Imidazolidines', 'Membrane Transport Modulators', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Phenytoin and Prodrugs', 'Prodrugs', 'Sodium Channel Blockers', 'Thyroxine-binding globulin substrates', 'UGT1A6 Inhibitors', 'UGT1A9 Inhibitors']" +DB00303,Ertapenem,Ertapenemis a carbapenem antibiotic used for the treatment of moderate to severe infections caused by susceptible bacteria.,"['P02918', 'P02919', 'P44469', 'P0AD65', 'P45059', 'P0AD68', 'P24228', 'P08506']","Ertapenem is a carbapenem antibiotic with time-dependent bactericidal activity.3,4Its optimal bactericidal activity is achieved when drug concentrations exceed the minimal inhibitory concentrations (MIC) for a specified portion of the dosing interval.2,3,4It works against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It is stable against hydrolysis by various beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases, but not metallo-beta-lactamases.5,6",[H][C@]12[C@@H](C)C(S[C@]3([H])CN[C@@]([H])(C3)C(=O)NC3=CC=CC(=C3)C(O)=O)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O,"Ertapenem exhibits a bactericidal mode of action.It works by binding to and inhibiting bacterial penicillin-binding proteins (PBPs).InEscherichia coli, it has a strong affinity toward PBPs a, b, , , and with preferential binding to PBPs and .Upon binding to PBPs, ertapenem inhibits bacterial cell wall synthesis by interfering with the lengthening and strengthening of the peptidoglycan portion of the cell wall, thereby inhibiting cell wall synthesis.TargetActionsOrganismAPenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)APenicillin-binding protein inhibitorEscherichia coli (strain K)APeptidoglycan synthase FtsIinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)APeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacBinhibitorEscherichia coli (strain K)AD-alanyl-D-alanine carboxypeptidase DacCinhibitorEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Carbapenems', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penem Antibacterial', 'Sulfur Compounds']" +DB00560,Tigecycline,Tigecyclineis a glycylcycline antibiotic used to treat a number of susceptible bacterial infections.,"['P0A7X3', 'P0A7S3', 'P0A7S9', 'P0AG59', 'P0A7U3']","Tigecycline is the first clinically-available drug in a new class of antibiotics called the glycylcyclines. Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines.",[H][C@@]12CC3=C(C(O)=C(NC(=O)CNC(C)(C)C)C=C3N(C)C)C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2,"Tigecycline, a glycylcycline, inhibits protein translation in bacteria by binding to the S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. Tigecycline carries a glycylamido moiety attached to the -position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. Tigecycline is not affected by the two major tetracycline resistance mechanisms, ribosomal protection and efflux. Accordingly, tigecycline has demonstrated in vitro and in vivo activity against a broad spectrum of bacterial pathogens. There has been no cross resistance observed between tigecycline and other antibiotics. Tigecycline is not affected by resistance mechanisms such as beta-lactamases (including extended spectrum beta-lactamases), target site modifications, macrolide efflux pumps or enzyme target changes (e.g. gyrase/topoisomerase). In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterial drugs. In general, tigecycline is considered bacteriostatic.TargetActionsOrganismAS ribosomal RNAbinderEnteric bacteria and other eubacteriaAS ribosomal protein SbinderEscherichia coli (strain K)AS ribosomal protein SbinderEscherichia coli (strain K)AS ribosomal protein SbinderEscherichia coli (strain K)AS ribosomal protein SbinderEscherichia coli (strain K)AS ribosomal protein SbinderEscherichia coli (strain K)",[],"['Agents that produce neuromuscular block (indirect)', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Enzyme Inhibitors', 'Glycylcyclines', 'Naphthacenes', 'Protein Synthesis Inhibitors', 'Tetracyclines']" +DB01579,Phendimetrazine,Phendimetrazineis a sympathomimetic amine used as adjunct therapy for the short term management of exogenous obesity.,"['P35348', 'P23975', 'P35368']","Phendimetrazine is a phenylalkylamine sympathomimetic amine with pharmacological activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance has been demonstrated with all drugs of this class in which these phenomena have been looked for. Drugs of this class used in obesity are commonly known as ''anorectics or anorexigenics."" It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved.",C[C@H]1[C@@H](OCCN1C)C1=CC=CC=C1,Phendimetrazine may act in a similar way to amphetamines in that it activates the alpha-adrenergic system to induce an appetite suppressive and metabolic increase effect. The drug also acts as a norepinephrine-dopamine releasing agent (NDRA). It can bind to and reverse the NET.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansASodium-dependent noradrenaline transporternegative modulatorHumansUAlpha-B adrenergic receptoragonistHumans,[],"['Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amphetamines', 'Appetite Suppression', 'Central Nervous System Agents', 'Central Nervous System Stimulants', 'Increased Sympathetic Activity', 'Oxazines', 'Sympathomimetic Amine Anorectic', 'Sympathomimetics']" +DB08934,Sofosbuvir,Sofosbuviris a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.,['O39930'],"Sofosbuvir acts against HCV and is categorized as a direct-acting antiviral agent (DAA).At a dose 3 times the recommended dose, sofosbuvir does not prolong QTc to any clinically relevant extentLabel.",CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](N2C=CC(=O)NC2=O)[C@](C)(F)[C@@H]1O)OC1=CC=CC=C1,"Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NSB (non-structural protein B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-), sofosbuvir incorporates into HCV RNA by the NSB polymerase and acts as a chain terminatorSynthesis,. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg+ ions present in HCV NSB polymerase's GDD active site motif and preventing further replication of HCV genetic material,Label.TargetActionsOrganismARNA-dependent RNA-polymeraseinhibitorHepatitis C Virus",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Substrates', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Hepatitis C Virus Nucleotide Analog NS5B Polymerase Inhibitor', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Nucleotides', 'P-glycoprotein substrates', 'Pyrimidine Nucleosides', 'Pyrimidine Nucleotides', 'Pyrimidines', 'Ribonucleosides', 'Ribonucleotides', 'RNA Replicase Inhibitors', 'Treatments for Hepatitis C', 'Uracil Nucleotides']" +DB01265,Telbivudine,Telbivudineis a thymidine nucleoside analog used for the treatment of chronic hepatitis B with clinical evidence of viral replication or persistent elevations in serum aminotransferases (ALT or AST).,['Q05486'],"Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate.",CC1=CN([C@@H]2C[C@@H](O)[C@H](CO)O2)C(=O)NC1=O,"Telbivudine '–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine '–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine '–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine inhibits anticompliment or second-strand DNA.TargetActionsOrganismADNANot AvailableHumansAProtein PNot AvailableHBV-F",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Deoxyribonucleosides', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside and Nucleotide Reverse Transcriptase Inhibitors', 'Nucleoside Reverse Transcriptase Inhibitors', 'Nucleosides', 'Nucleosides and Nucleotides', 'Pyrimidine Nucleosides', 'Pyrimidines']" +DB00547,Desoximetasone,Desoximetasoneis a glucocorticoid used to treat inflammatory and pruritic corticosteroid-responsive dermatoses.,['P04150'],"Like other topical corticosteroids, desoximetasone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Desoximetasone is a potent topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved.",[H][C@@]12C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase Ainhibitory proteins, collectively called lipocortins. This is achieved first by the drug binding to the glucocorticoid receptors which then translocates into the nucleus and binds to DNA causing various activations and repressions of genes. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Pregnadienediols', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated']" +DB13943,Testosterone cypionate,Testosterone cypionateis an androgen used to treat low or absent testosterone.,"['P10275', 'P03372', 'P08235']",Administration of ester derivatives of testosterone as testosterone cypionate generates an increase in serum testosterone to levels reaching 400% from the baseline within 24 hours of administration. These androgen levels remain elevated for 3-5 days after initial administration.3The continuous variation in plasma testosterone after intramuscular administration of testosterone cypionate results in fluctuations in mood and libido as well as some local inflammation.4,[H][C@@]12CC[C@H](OC(=O)CCC3CCCC3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C,"The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to -alpha-dihydrotestosterone (DHT) by the cytoplasmic enzyme -alpha-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about . times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.TargetActionsOrganismAAndrogen receptoragonistHumansUEstrogen receptor alphaNot AvailableHumansUMineralocorticoid receptorNot AvailableHumans",[],"['Anabolic Agents', 'Androgens', 'Androstanes', 'Androstenes', 'Androstenols', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Delayed-Action Preparations', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OAT3/SLC22A8 Inducers', 'P-glycoprotein inhibitors', 'Steroids', 'Testosterone and derivatives', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors']" +DB00984,Nandrolone phenpropionate,C18 steroid with androgenic and anabolic properties. It is generally prepared from alkyl ethers of estradiol to resemble testosterone but less one carbon at the 19 position. It is a schedule III drug in the U.S.,['P10275'],"Nandrolone is an anabolic steroid occurring naturally in the human body, albeit in small quantities. Nandrolone increases production and urinary excretion of erythropoietin. It may also have a direct action on bone marrow. Nandrolone binds to the androgen receptor to a greater degree than testosterone, but due to its inability to act on the muscle in ways unmediated by the receptor, has less overall effect on muscle growth.",[H][C@@]12CC[C@H](OC(=O)CCC3=CC=CC=C3)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H],"Nandrolone is an androgen receptor agonist. The drug bound to the receptor complexes which allows it to enter the nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.TargetActionsOrganismAAndrogen receptoragonistHumans",[],"['Anabolic Agents', 'Androgens', 'Estranes', 'Estrenes', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Nandrolone and esters', 'Steroids', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors']" +DB09289,Tianeptine,Tianeptineis an atypical tricyclic antidepressant with antidepressant and anxiolytic effects primarily used to treat major depressive disorder.,"['P35372', 'P42261', 'P08908', 'P35462']","Analyses in large-scale epidemiologic surveys have shown that the anxiety disorders are widely comorbid with major depression. This makes antidepressant with anxiolytic properties particularly unique and attractive2.Tianeptine is effective in reducing depressive symptoms in mild to severe major depressive disorder and also alleviates anxious symptoms associated with depression without the need for coadministration of an anti-anxiety medication2.These findings, however, are met with controversial data. In a study of healthy volunteers, Tianeptine-treated subjects were less accurate at identifying facial expressions, suggesting a lack of improvement in the psychomotor symptoms of depression. The tianeptine group also showed reduced memory and reduced attentional vigilance to various stimuli6.",CN1C2=CC=CC=C2C(NCCCCCCC(O)=O)C2=C(C=C(Cl)C=C2)S1(=O)=O,"Recent studies suggest that tianeptine acts as a full agonist at the mu-type opioid receptor (MOR),. The mu opioid receptors are currently being studied as effective targets for antidepressant therapies. It is believed that the clinical effects of tianeptine are owed to its modulation of these receptors. In addition to its actions on the opioid receptor, previous studies have owed its action to its effect on the serotonin receptor,, dopamine (D/) receptors, and glutamate receptors,, as discussed below:Tianeptine has challenged the monoaminergic hypothesis of depression, as well as the widely supported monoaminergic mechanisms whereby the action of most known antidepressants have been explained. Specifically, this drug is thought to persistently alter glutamate receptor bursting of the hippocampal CA commissural associational synapse. Current research suggests that tianeptine produces its antidepressant effects through the modulation of glutamate receptor activity (for example, AMPA receptors and NMDA receptors) and affect the release of brain-derived neurotrophic factor (BDNF), which impacts neural plasticity. More recent studies by support the role of tianeptine in the modulation of glutaminergic activity in the amygdala, the emotional region of the brain associated with memories.Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, and thus prevents stress-related behavioral issues,. In rodents, the stress of acute restraint increases extracellular levels of glutamate in the basolateral amygdala an effect that was inhibited by tianeptine. Interestingly, the SSRI fluoxetine increased extracellular glutamate levels in the basolateral amygdala regardless of stress conditions. These data demonstrate that the mechanism of action of tianeptine is distinct from SSRIs and support the hypothesis that the mechanism of action of tianeptine relates to alteration of glutaminergic activity in the amygdala and the hippocampus,,.In addition to the above mechanisms, tianeptine is a unique antidepressant and anxiolytic medication that stimulates the uptake of serotonin (-hydroxytryptamine; -HT), and -hydroxyindoleacetic acid (-HIAA) in brain tissue.Although the monoaminergic neurotransmitters serotonin (-HT), noradrenaline (NA) and dopamine (DA) are proven to be related to the occurrence of depressive disorders, it is now recognized that monoamine deficits are not sufficient to explain the mechanism of action of antidepressant medications.TargetActionsOrganismAMu-type opioid receptoragonistHumansUGlutamate receptor modulatorHumansU-hydroxytryptamine receptor AinhibitorHumansUDopamine D receptoragonistHumans",[],"['Agents Causing Muscle Toxicity', 'Agents that produce hypertension', 'Agents that reduce seizure threshold', 'Analgesics', 'Antidepressive Agents', 'Antidepressive Agents, Tricyclic', 'Azepines', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Narrow Therapeutic Index Drugs', 'Nervous System', 'Neurotoxic agents', 'Psychoanaleptics', 'Psychotropic Drugs', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Sulfur Compounds', 'Thiepins']" +DB13751,Glycyrrhizic acid,"Glycyrrhizic acid is extracted from the root of the licorice plant;Glycyrrhiza glabra.11It is a triterpene glycoside with glycyrrhetinic acid that possesses a wide range of pharmacological and biological activities. When extracted from the plant, it can be obtained in the form of ammonium glycyrrhizin and mono-ammonium glycyrrhizin.8Glycyrrhizic acid has been developed in Japan and China as a hepatoprotective drug in cases of chronic hepatitis.1From January 2014, glycyrrhizic acid as part of the licorice extract was approved by the FDA as an existing food sweetener.12It was approved by Health Canada to be used in over-the-counter products but all the products are currently on the status canceled post marketed.10","['P28845', 'P01375', 'P42574', 'Q00653', 'P19838', 'P06858']","Glycyrrhizic acid was reported to present antiallergic, antiviral and anti-inflammatory activities as well as improvements in glucose tolerance.1The effect of glycyrrhizic acid in metabolic syndrome generates a significant decrease in blood glucose, fasting blood glucose and mean serum insulin concentration.2",[H][C@@]12C[C@](C)(CC[C@]1(C)CC[C@]1(C)C2=CC(=O)[C@]2([H])[C@@]3(C)CC[C@H](O[C@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4O[C@@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4O)C(O)=O)C(O)=O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)=O,"Glycyrrhizic acid can be found in the alpha and beta forms. The alpha form is predominant in the liver and duodenum and thus, it is thought that the anti-inflammatory liver effect of this drug are mainly due to the action of this isomer. Glycyrrhizic acid anti-inflammatory effect is generated via suppression of TNF alpha and caspase . It also inhibits the translocation of NFkB into the nuclei and conjugates free radicals. Some studies have shown a glycyrrhizic-driven inhibition of CD+ T cell proliferation via JNK, ERK and PIK/AKT.The antiviral activity of glycyrrhizic acid includes the inhibition of viral replication and immune regulation.The antiviral activity of glycyrrhizic acid seems to be of a broad spectrum and be able to cover several different viral types such as vaccinia virus, herpes simplex virus, Newcastle disease virus and vesicular stomatitis virus.The effect of glycyrrhizic acid on metabolism is thought to be related to its inhibitory activity towards -beta-hydroxysteroid dehydrogenase type which in turn decreases the activity of hexose--phosphate dehydrogenase. On the other hand, some studies have shown a potential lipoprotein lipase induction in non-hepatic tissues and thus it is suggested to enhance dyslipidemic conditions.TargetActionsOrganismACorticosteroid -beta-dehydrogenase isozyme antagonistHumansATumor necrosis factorantagonistHumansACaspase-antagonistHumansANuclear factor NF-kappa-Btranslocation inhibitorHumansALipoprotein lipaseinducerHumans",[],"['Alimentary Tract and Metabolism', 'Anti-Inflammatory Agents', 'Bile and Liver Therapy', 'BSEP/ABCB11 Substrates', 'Liver Therapy', 'Liver Therapy, Lipotropics', 'Pentacyclic Triterpenes', 'Terpenes', 'Triterpenes']" +DB00910,Paricalcitol,Paricalcitolis a vitamin D analog used to treat hyperparathyroidism associated with stage 3 or greater chronic kidney disease.,['P11473'],"Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin and from dietary intake. Vitamin D requires two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR). The endogenous VDR activator, calcitriol [1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone. In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis.1 Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy. An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL).",[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1C[C@@H](O)C[C@H](O)C1)[C@H](C)\C=C\[C@H](C)C(C)(C)O,"Paricalcitol is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D) and the A (-nor) ring. Preclinical andin vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.TargetActionsOrganismAVitamin D receptoragonistHumans",[],"['Anti-Parathyroid Agents', 'Bone Density Conservation Agents', 'Calcium Homeostasis', 'Cholestanes', 'Cholestenes', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Lipids', 'Membrane Lipids', 'Secosteroids', 'Steroids', 'Sterols', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'UGT1A4 substrates', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB01425,Alizapride,"Alizaprideis a dopamine antagonist used to prevent nausea and vomiting associated with medical procedures, surgeries, and cancer therapies.",['P14416'],Alizapride is a dopamine antagonist.,COC1=CC2=NNN=C2C=C1C(=O)NCC1CCCN1CC=C,"The anti-emetic action of Alizapride is due to its antagonist activity at D receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)—this action prevents nausea and vomiting triggered by most stimuli. Structurally similar to metoclopramide and, therefore, shares similar other atributres related to emesis and prokinetics.TargetActionsOrganismADopamine D receptorantagonistHumans",['Antiemetics'],"['Alimentary Tract and Metabolism', 'Antiemetics', 'Autonomic Agents', 'Central Nervous System Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs for Functional Gastrointestinal Disorders', 'Gastrointestinal Agents', 'Peripheral Nervous System Agents', 'Propulsives']" +DB03516,Eniluracil,"Eniluracil, which was previously under development by GlaxoSmithKline (GSK), is being developed by Adherex to enhance the therapeutic value and effectiveness of 5-fluorouracil (5-FU), one of the world’s most widely-used oncology agents. 5-FU is widely used in the U.S. and is often first or second line therapy for a variety of cancers including colorectal, breast, gastric, head and neck, ovarian and basal cell cancer of the skin. Eniluracil could improve 5-FU by increasing its effectiveness, reducing its side effects and/or making it orally available. Eniluracil has received Orphan Drug status from the FDA for the treatment of hepatocellular cancer in combination with fluoropyrimidines (including 5-FU).","['Q06278', 'P47989', 'Q12882']","Eniluracil is an orally active dihydropyrimidine dehydrogenase (DPD) inhibitor, designed to enhance activity of chemotaxic agents. It is under investigation by Adherex, under license from GlaxoSmithKline, for the treatment of cancer in combination with 5-fluorouracil (5-FU).",O=C1NC=C(C#C)C(=O)N1,"Normally, -FU is rapidly broken down in the body by an enzyme known as dihydropyrimidine dehydrogenase (DPD). Eniluracil irreversibly inhibits DPD, thereby substantially slowing the breakdown of -FU and prolonging exposure of the tumor cells to the drug.TargetActionsOrganismUAldehyde oxidaseNot AvailableHumansUXanthine dehydrogenase/oxidaseinhibitorHumansUDihydropyrimidine dehydrogenase [NADP(+)]Not AvailableHumans",[],"['Enzyme Inhibitors', 'Pyrimidines', 'Pyrimidinones']" +DB01117,Atovaquone,Atovaquoneis an antimicrobial indicated for the prevention and treatment of Pneumocystis jirovecii pneumonia (PCP) and for the prevention and treatment of Plasmodium falciparum malaria.,"['Q02768', 'Q08210', 'Q02127']","Atovaquone is a highly lipophilic drug that closely resembles the structureubiquinone. Its inhibitory effect being comparable to ubiquinone, atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis in atovaquone-responsive parasites. Cytochrome bc1 complex (complex III) seems to serve as a highly discriminating molecular target for atovaquone in Plasmodia. There is no significant risk for myelosuppression associated with atovaquone, making this drug a beneficial therapeutic agent for recipients of bone marrow transplantation.",OC1=C([C@H]2CC[C@@H](CC2)C2=CC=C(Cl)C=C2)C(=O)C2=CC=CC=C2C1=O,"The mechanism of action againstPneumocystis cariniihas not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes. The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis. Atovaquone also has been shown to have goodin vitroactivity againstToxoplasma gondii.TargetActionsOrganismACytochrome binhibitorPlasmodium falciparumADihydroorotate dehydrogenase (quinone), mitochondrialinhibitorPlasmodium falciparum (isolate D)UDihydroorotate dehydrogenase (quinone), mitochondrialinhibitorHumans",[],"['Anti-Infective Agents', 'Antibiotics for Pneumocystis Pneumonia', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Biguanides', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Miscellaneous Antiprotozoals', 'Naphthalenes', 'Naphthoquinones', 'P-glycoprotein inhibitors', 'Quinones']" +DB00478,Rimantadine,Rimantadineis an RNA synthesis inhibitor used to prevent influenza A infection.,['P21430'],"Rimantadine, a cyclic amine, is a synthetic antiviral drug and a derivate of adamantane, like a similar drug amantadine. Rimantadine is inhibitory to the in vitro replication of influenza A virus isolates from each of the three antigenic subtypes (H1N1, H2H2 and H3N2) that have been isolated from man. Rimantadine has little or no activity against influenza B virus. Rimantadine does not appear to interfere with the immunogenicity of inactivated influenza A vaccine.",CC(N)C12CC3CC(CC(C3)C1)C2,"The mechanism of action of rimantadine is not fully understood. Rimantadine appears to exert its inhibitory effect early in the viral replicative cycle, possibly inhibiting the uncoating of the virus. The protein coded by the M gene of influenza A may play an important role in rimantadine susceptibility.TargetActionsOrganismAMatrix protein other/unknownInfluenza A virus (strain A/Ann Arbor// HN)",[],"['Adamantanes', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Bridged-Ring Compounds', 'Cyclic Amines', 'Cycloparaffins', 'Enzyme Inhibitors', 'Influenza A M2 Protein Inhibitor', 'M2 Protein Inhibitors', 'Nucleic Acid Synthesis Inhibitors']" +DB00869,Dorzolamide,Dorzolamideis a carbonic anhydrase inhibitor used to treat high intraocular pressure in ocular hypertension and open angle glaucoma.,"['P00918', 'P22748', 'P00915', 'P07451']","Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension. When used in combination with topic beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure. The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.2",CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O,"Elevated intraocular pressure is a characteristic manifestation of ocular hypertension or open-angle glaucoma. The level of intraocular pressure (IOP) is governed by the balance between the production of aqueous humour (by ocular ciliary processes) and its outflow from the anterior segment of the eye via trabecular (conventional) or uveoscleral (unconventional) pathways. When there is an increase in the resistance to the trabecular outflow of aqueous humour, the intraocular pressure is elevated. Subsequently, optic nerve damage can occur from blood flow restrictions and mechanical distortion of ocular structures. Optic nerve damage can further result in optic disc cupping and progressive visual field loss (and blindness in some cases).Carbonic anhydrase (CA) is a ubiquitous enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate ions and dehydration of carbonic acid.,In the ocular ciliary processes, the local production of bicarbonate by CAs promotes sodium and fluid transport. CA-II is a key isoenzyme found primarily in red blood cells (RBCs) that regulates aqueous humour production.Dorzolamide is a highly specific CA-II inhibitor, where it displays a -fold higher affinity for carbonic anhydrase II than carbonic anhydrase I.The inhibition of CA-II in the ciliary process disrupts the formation of bicarbonate ions and reduces sodium and fluid transport, which leads to decreased aqueous humour secretion and reduced intraocular pressure.,TargetActionsOrganismACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Amides', 'Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Carbonic Anhydrase Inhibitors', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Substrates', 'Diuretics', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Intraocular Pressure, drug effects', 'Ophthalmologicals', 'Sensory Organs', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB00287,Travoprost,Travoprostis a prostaglandin analog used in the treatment of elevated intraocular pressure due to open angle glaucoma or ocular hypertension.,['P43088'],"Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analog that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acidLabel. The travoprost free acid is potent and highly selective for the FP prostanoid receptorLabel.",CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(=C1)C(F)(F)F,"Travoprost, a prostaglandin Fα analogue, is a highly selective full agonist which has a high affinity for the prostaglandin FP receptor, and facilitates reductions in intraocular pressure by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways,,. Reduction of the intraocular pressure in man starts about hours after administration and maximum effect is reached after hours. Significant lowering of intraocular pressure can be maintained for periods exceeding hours with a single dose,,.TargetActionsOrganismAProstaglandin F-alpha receptoragonistHumans",[],"['Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Inflammation Mediators', 'Lipids', 'Ophthalmics', 'Ophthalmologicals', 'Prostaglandin analogs reducing intraocular pressure (IOP)', 'Prostaglandins', 'Prostaglandins F, Synthetic', 'Prostaglandins, Synthetic']" +DB00654,Latanoprost,Latanoprostis an isopropyl ester prodrug used to treat increased intraocular pressure.,['P43088'],"Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow.2A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours.3A note on eye and periorbital changesBetween 3 to 10% of patients taking latanoprost have experienced iris pigmentation after about 3-4 months of latanoprost use.1,2Patients should be notified of this risk before initiating treatment. It may occur in both patients with light-colored irides (green-brown or blue/grey-brown) or dark-colored (brown) irides, but is less pronounced in the latter group.1This drug may also cause other ocular effects including infrequent conjunctival hyperemia, pigmentation of periocular tissues, eyelash changes, hypertrichosis, and ocular irritation.3,6",CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1,"Elevated intraocular pressure leads to an increased risk of glaucomatous visual field loss. The higher the intraocular pressure, the higher the risk of damage to the optic nerve and loss of visual field.Latanoprost selectively stimulates the prostaglandin F alpha receptor and this results in a decreased intraocular pressure (IOP) via the increased outflow of aqueous humor, which is often implicated in cases of elevated intraocular pressure.,Possible specific mechanisms of the abovementioned increased aqueous outflow are the remodeling of the extracellular matrix and regulation of matrix metalloproteinases. These actions result in higher tissue permeability related to humor outflow pathways, which likely change outflow resistance and/or outflow rates.TargetActionsOrganismAProstaglandin F-alpha receptoragonistHumans",[],"['Antiglaucoma Preparations and Miotics', 'Antihypertensive Agents', 'Autacoids', 'Biological Factors', 'Compounds used in a research, industrial, or household setting', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Lipids', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Ophthalmic Solutions', 'Ophthalmologicals', 'Pharmaceutical Preparations', 'Pharmaceutical Solutions', 'Prostaglandin analogs reducing intraocular pressure (IOP)', 'Prostaglandins', 'Prostaglandins F, Synthetic', 'Prostaglandins, Synthetic', 'Sensory Organs', 'Solutions']" +DB00449,Dipivefrin,Dipivefrinis a prodrug of epinephrine used in ophthalmic solutions to reduce intraocular pressure in chronic open-angle glaucoma.,"['P35348', 'P08913', 'P07550', 'P06276', 'P22303']","Dipivefrin is a member of a class of drugs known as prodrugs. Prodrugs are usually not active in themselves and require biotransformation to the parent compound before therapeutic activity is seen. These modifications are undertaken to enhance absorption, decrease side effects and enhance stability and comfort, thus making the parent compound a more useful drug. Enhanced absorption makes the prodrug a more efficient delivery system for the parent drug because less drug will be needed to produce the desired therapeutic response. Dipivefrin is a prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid. The addition of pivaloyl groups to the epinephrine molecule enhances its lipophilic character and, as a consequence, its penetration into the anterior chamber.",CNCC(O)C1=CC(OC(=O)C(C)(C)C)=C(OC(=O)C(C)(C)C)C=C1,"Dipivefrin is a prodrug with little or no pharmacologically activity until it is hydrolyzed into epinephrine inside the human eye. The liberated epinephrine, an adrenergic agonist, appears to exert its action by stimulating α -and/or β-adrenergic receptors, leading to a decrease in aqueous production and an enhancement of outflow facility. The dipivefrin prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are associated with conventional epinephrine therapy.TargetActionsOrganismAAlpha-A adrenergic receptoragonistHumansAAlpha-A adrenergic receptoragonistHumansABeta- adrenergic receptoragonistHumansACholinesterasesubstrateHumansUAcetylcholinesteraseinhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic alpha-1 Receptor Agonists', 'Adrenergic alpha-2 Receptor Agonists', 'Adrenergic alpha-Agonists', 'Adrenergic beta-1 Receptor Agonists', 'Adrenergic beta-2 Receptor Agonists', 'Adrenergic beta-3 Receptor Agonists', 'Adrenergic beta-Agonists', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antiglaucoma Preparations and Miotics', 'Benzene Derivatives', 'Biogenic Amines', 'Biogenic Monoamines', 'Catecholamines', 'Catechols', 'Cholinesterase substrates', 'Ethanolamines', 'Mydriatics', 'Neurotransmitter Agents', 'Ophthalmics', 'Ophthalmologicals', 'Phenols', 'Sensory Organs', 'Sympathomimetics in Glaucoma Therapy']" +DB01194,Brinzolamide,Brinzolamideis a carbonic anhydrase inhibitor used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.,"['P00918', 'P00915', 'P22748', 'P35218', 'P07451']","Inhibition of carbonic anhydrase II (CA-II) in the ciliary process of the eye slows the formation of bicarbonate and thus fluid flow, lowering intraocular pressure (IOP).3,4The IOP-reducing effect of brinzolamide as adjunctive therapy to the prostaglandin analog travoprost was studied. Following a 4-week run-in with travoprost, patients with an IOP ≥19 mmHg were randomized to receive added treatment with brinzolamide or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the brinzolamide group and 3.2 to 4.2 mmHg for the timolol group were observed. There was an overall higher incidence of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies.11A clinical trial was conducted with brinzolamide in 32 pediatric patients less than 6 years of age, diagnosed with glaucoma or ocular hypertension. Some patients were naive to IOP therapy whilst others were on other IOP-lowering medicinal product(s). Those who had been on previous IOP medicinal products were not required to discontinue their IOP medicinal product(s) until the initiation of monotherapy with brinzolamide.11Among patients who were naive to IOP therapy (10 patients), the efficacy of brinzolamide was similar to that seen previously in adults, with mean IOP reductions from baseline ranging up to 5 mmHg. Among patients who were on topical IOP-lowering medicinal products (22 patients), mean IOP increased slightly from baseline in the brinzolamide group.11",CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O,"Brinzolamide is a highly specific, reversible, non-competitive inhibitor of carbonic anhydrases (CA), the enzymes catalyzing the reversible reaction of water and carbon dioxide (CO) to form bicarbonate ions.Although there are isoforms of CA in human tissues, brinzolamide has the highest affinity to CA II.,Brinzolamide and its active metabolites were not found to displace any known ligands in vitro from their respective receptors or enzymes commonly involved in producing side effects or ancillary pharmacology, thus explaining brinzolamide's high order of safety.TargetActionsOrganismACarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase A, mitochondrialinhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Amides', 'Antiglaucoma Preparations and Miotics', 'Carbonic Anhydrase Inhibitors', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Diuretics', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Ophthalmics', 'Ophthalmologicals', 'Sensory Organs', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB06809,Plerixafor,Plerixaforis a CXCR4 antagonist used in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma.,['P61073'],"Plerixafor is a bicyclam derivative that antagonizes C-X-C chemokine receptor type 4 (CXCR4) by binding to three acidic residues in the ligand-binding pocket: Asp171, Asp262, and Glu288.7,10Blood levels of CD34+ cells peaked between 6 and 9 hours after the administration of 0.24 mg/kg plerixafor in healthy subjects. In combination with a granulocyte-colony stimulating factor (G-CSF), circulating CD34+ cells in the peripheral blood peaked between 10 and 14 hours. The use of plerixafor is not associated with QT/QTc prolongation at single doses up to 0.40 mg/kg.9Serious hypersensitivity reactions, such as anaphylactic-type reactions, have occurred in patients receiving plerixafor. The use of plerixafor may also cause tumor cell mobilization in leukemia patients, splenic enlargement and rupture, embryo-fetal toxicity, and hematologic effects, such as leukocytosis and thrombocytopenia. When used in combination with G-CSF for hematopoietic stem cell mobilization‚ plerixafor may lead to the release of tumor cells from the marrow and their subsequent collection in the leukapheresis product.9",C(N1CCCNCCNCCCNCC1)C1=CC=C(CN2CCCNCCNCCCNCC2)C=C1,"Plerixafor inhibits the C-X-C chemokine receptor type (CXCR) on CD+ cells and reversibly blocks the binding of its ligand, stromal cell-derived factor--alpha (SDF-α). SDF-α and CXCR play a role in the trafficking and homing of human hematopoietic stem cells (HSCs) to the marrow compartment. In the marrow, stem cell CXCR can help anchor HSCs to the marrow matrix, either directly via SDF-α or through the induction of other adhesion molecules. By blocking the interaction between SDF-α and CXCR with plerixafor, the mobilization of progenitor cells is triggered. Adding granulocyte-colony stimulating factor (G-CSF) to enhance CD+ cell mobilization increases the yield of stem cells, an important determinant of graft adequacy.,,TargetActionsOrganismAC-X-C chemokine receptor type antagonistinhibitorHumans",['Mobilization of hematopoietic stem cells'],"['Adjuvants, Immunologic', 'Amines', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Antineoplastic and Immunomodulating Agents', 'Benzene Derivatives', 'Benzyl Compounds', 'Drugs that are Mainly Renally Excreted', 'Hematinics', 'Hematopoietic Stem Cell Mobilizer', 'Increased Hematopoietic Stem Cell Mobilization', 'Polyamines']" +DB01055,Mimosine,Mimosine is an antineoplastic alanine-substituted pyridine derivative isolated fromLeucena glauca.,"['P34896', 'P13500', 'P14679']",Mimosine inhibits DNA synthesis at the level of elongation of nascent chains by altering deoxyribonucleotide metabolism. It arrests the cell cycle in the late G(1) phase.,N[C@@H](CN1C=CC(=O)C(O)=C1)C(O)=O,"Mimosine causes inhibition of DNA replication, changes in the progression of the cells in the cell cycle, and apoptosis. Mimosine appears to introduce breaks into DNA. Mimosine is an iron/zinc chelator. Iron depletion induces DNA double-strand breaks in treated cells, and activates a DNA damage response that results in focal phosphorylation of histones. This leads to inhibition of DNA replication and/or DNA elongation. Some studies indicate that mimosine prevents the initiation of DNA replication, whereas other studies indicate that mimosine disrupts elongation of the replication fork by impairing deoxyribonucleotide synthesis by inhibiting the activity of the iron-dependent enzyme ribonucleotide reductase and the transcription of the cytoplasmic serine hydroxymethyltransferase gene (SHMT). Inhibition of serine hydroxymethyltransferase is moderated by a zinc responsive unit located in front of the SHMT gene.TargetActionsOrganismASerine hydroxymethyltransferase, cytosolicinhibitorHumansAC-C motif chemokine inhibitorHumansUTyrosinaseinhibitorHumans",[],"['Alanine', 'Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Pyridines', 'Pyridones']" +DB00719,Azatadine,Azatadineis an H1 receptor antagonist used to treat perennial and allergic rhinitis as well as eustachian tube congestion.,['P35367'],"Azatadine is an antihistamine, related to cyproheptadine, with anti-serotonin, anticholinergic (drying), and sedative effects. Azatadine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, azatadine is not used clinically as an anti-psychotic. Antihistamines antagonize the vasodilator effect of endogenously released histamine, especially in small vessels, and mitigate the effect of histamine which results in increased capillary permeability and edema formation. As consequences of these actions, antihistamines antagonize the physiological manifestations of histamine release in the nose following antigen-antibody interaction, such as congestion related to vascular engorgement, mucosal edema, and profuse, watery secretion, and irritation and sneezing resulting from histamine action on afferent nerve terminals.",CN1CCC(CC1)=C1C2=CC=CC=C2CCC2=C1N=CC=C2,Antihistamines such as azatadine appear to compete with histamine for histamine H- receptor sites on effector cells. The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H- receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release.TargetActionsOrganismAHistamine H receptorantagonistHumans,[],"['Agents that reduce seizure threshold', 'Anticholinergic Agents', 'Antihistamines for Systemic Use', 'Benzocycloheptenes', 'Cholinergic Agents', 'Dibenzocycloheptenes', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Piperidines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB06153,Pizotifen,Pizotifenis a serotonin and tryptamine antagonist indicated for migraine prophylaxis.,"['P11229', 'P08172', 'P20309', 'P28223', 'P41595', 'P28335', 'P08908', 'P28222', 'P35367', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Various studies have shown pizotifen to be effective in the prophylaxis of migraines in reducing the frequency and severity of vascular headaches3. Evidence from studiesin vivoandin vitrodemonstrate antagonistic actions towards serotonin and histamine. Pizotifen blocks the postsynaptic 5-HT2 receptors, as supported by antagonism of several direct agonists of 5-HT receptors5. It is an antagonist at histamine H1 receptors, and is weakly anticholinergic9. It also binds to α1- and α2-adrenergic receptors, and dopamine receptors9. Pizotifen elicits a minimal effect as an epinephrine or bradykinin antagonist10. Pizotifen exhibits weak sedative properties in mouse and monkey studies, as indicated by inhibition of locomotion and potentiation of barbiturates, without changes in cardiac or respiratory rates10. In dogs, intravenous administration of pizotifen cause rapid hypotension but was reversed to normal within 30 minutes10. Pizotifen was shown to inhibit serotonin uptake in the isolated perfused cat spleen and,in vivo, inhibits serotonin-induced contractions in rat uterus and cat nictiating membrane2. In contrast, pizotifen demonstrated a venoconstrictor activityin vivowhen orally or intravenously administered to saphenous veins in conscious dogs4. Pizotifen has the potential to stimulate the appetite and may cause weight gain upon treatment2.In a double-blind clinical study of patients with mild to moderate depression, treatment of pizotifen led to clinical improvement of the depressive symptoms. However, deterioration of the schizophrenic emotional symptoms was also observed in patients with depression and chronic schizophrenia1. This indicates that pizotifen may potentially improve the symptoms of patients with depressions in conjunction with migraines1.Neuroprotective effect of pizotifen was investigatedin vitroin a mouse cell model of Huntington's disease (HD). According to a chemical screen of a mouse HdhQ111/Q111 striatal cell model of HD, treatment of pizotifen was associated with increased ATP levels and decreased activation of caspase-3, leading to enhanced cell viability6. Transient activation of ERK signalling pathway lasting for less than 3 hours was also observed. In the R6/2 transgenic mouse model of HD, rotarod performance of the mouse treated with pizotifen was seen, accompanied by an increase in DARPP-32 protein expression and restoration of striatal area6. However these effects being reflectedin vivoare not established.",CN1CCC(CC1)=C1C2=C(CCC3=CC=CC=C13)SC=C2,"While the mechanism of action is not fully understood, it is proposed that pizotifen works by inhibiting the peripheral actions of serotonin and histamine in increasing the membrane permeability of cranial vessels and transudation of plasmakinin, while altering pain thresholds in migraines. By blocking -HT receptors, pizotifen attenuates the signalling of serotonin in causing cranial vasoconstriction, as well as serotonin-enhanced platelet function and aggregation,. There is evidence that it also inhibits the peripheral actions of bradykinin. Pizotifen may inhibit serotonin reuptake by blood platelets, which affects the tonicity and decreases passive distension of extracranial arteries. The effects of pizotifen leading to appetite stimulation may be due to the drug acting at the metabolic level rather than a direct stimulation of the appetite centre.TargetActionsOrganismUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansUMuscarinic acetylcholine receptor MantagonistHumansU-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumansU-hydroxytryptamine receptor CantagonistHumansU-hydroxytryptamine receptor Apartial agonistHumansU-hydroxytryptamine receptor BantagonistHumansUHistamine H receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-D adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAlpha-C adrenergic receptorantagonistHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anticholinergic Agents', 'Antidepressive Agents', 'Antimigraine Agents, Miscellaneous', 'Antimigraine Preparations', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Muscarinic Antagonists', 'Nervous System', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Psychotropic Drugs', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin 5-HT2C Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists', 'Sulfur Compounds', 'Thiophenes']" +DB00464,Sodium tetradecyl sulfate,Sodium tetradecyl sulfateis an anionic surfactant used to treat varicose veins of the lower extremities.,"['P07225', 'P04070']","Sodium tetradecyl sulfate is an anionic surfactant which occurs as a white, waxy solid. It is used as a sclerosing agent in sclerotherapy. Sclerotherapy is an injection of a sclerosing agent directly through the skin into a lesion and is used primarily for slow-flow vascular anomalies, particularly for venous malformation and lymphatic malformation. Intravenous injection causes intima inflammation and thrombus formation. This usually occludes the injected vein. Subsequent formation of fibrous tissue results in partial or complete vein obliteration that may or may not be permanent.",[Na+].CCCCC(CC)CCC(CC(C)C)OS([O-])(=O)=O,"Sodium tetradecyl sulfate is a potent toxin for endothelial cells in that brief exposure to even low concentrations are effective in stripping endothelium over a considerable distance and exposing highly thrombogenic endothelium in the process. Diluted sodium tetradecyl sulfate is also able to induce a hypercoagulable state, possibly by selective inhibition of protein C, and can also promote platelet aggregation.TargetActionsOrganismAVitamin K-dependent protein SinhibitorHumansAVitamin K-dependent protein CinhibitorHumans",[],"['Acids', 'Alcohols', 'Alkanesulfonates', 'Alkanesulfonic Acids', 'Antivaricose Therapy', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Fatty Alcohols', 'Lipids', 'Pharmaceutical Preparations', 'Pharmaceutical Solutions', 'Sclerosing Agents for Local Injection', 'Sclerosing Solutions', 'Solutions', 'Sulfonic Acids', 'Sulfur Acids', 'Sulfur Compounds', 'Surface-Active Agents', 'Vasoprotectives']" +DB00552,Pentostatin,Pentostatinis an adenosine deaminase inhibitor used to treat hairy cell leukemia.,['P00813'],"Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the ""S"" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).",OC[C@H]1O[C@H](C[C@@H]1O)N1C=NC2=C1N=CNC[C@H]2O,"Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).TargetActionsOrganismAAdenosine deaminaseinhibitorHumans",[],"['Adenosine Deaminase Inhibitors', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cancer immunotherapy', 'Cardiotoxic antineoplastic agents', 'Coformycin', 'Deoxyribonucleosides', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Enzyme Inhibitors', 'Formycins', 'Immunosuppressive Agents', 'Immunotherapy', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'Pyrimidine Nucleosides', 'Pyrimidines']" +DB08836,Temocapril,"Temocapril is a prodrug-type angiotensin-I converting enzyme (ACE) inhibitor not approved for use in the United States, but is approved in Japan and South Korea. Temocapril can also be used in hemodialysis patients without risk of serious accumulation.",['P12821'],"Temocapril is a prodrug of its active metabolite (and diacid form) temocaprilat which contains a thiazepine ring. Temocaprilat has slightly higher potency than enalaprilat in ACE inhibition isolated from rabbit lung. ACE inhibitors exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.). When compared with other Angiotensin-converting Enzyme Inhibitors, temocapril's advantages include a rapid onset of action and what research suggests is tighter vascular ACE binding than enalaprilat.",CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CS[C@@H](CN(CC(O)=O)C1=O)C1=CC=CS1,TargetActionsOrganismUAngiotensin-converting enzymeinhibitorHumans,[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Angiotensin-Converting Enzyme Inhibitors', 'Antihypertensive Agents', 'Azepines', 'Cardiovascular Agents', 'Enzyme Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'Protease Inhibitors', 'Sulfur Compounds', 'Thiepins']" +DB01583,Liotrix,"Liotrix is a synthetically derived thyroid hormone replacement preparation. It consists of levothyroxine sodium (thyroxine, T4) and liothyronine sodium (triiodothyronine, T3) in a 4 to 1 ratio by weight. Liotrix was developed when it was believed that serum levels of both T4 and T3 were maintained by direct thyroidal secretion. It is now known that the thyroid gland secretes approximately ten times more T4 than T3 and that 80% of serum T3 is derived from deiodination of T4 in peripheral tissues. Administration of levothyroxine alone is sufficient for maintaining serum T4 and T3 levels in most patients and combination hormone replacement therapy generally offers no therapeutic advantage. In fact, administration of T3 may result in supratherapeutic levels of T3.","['P10827', 'P10828']","Thyroid hormone drugs are natural or synthetic preparations containing T4or T3or both. T4and T3are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. Liotrix is a synthetic preparation of T4 and T3 in a 4:1 weight-based ratio. These hormones enhance oxygen consumption by most tissues of the body and increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system.",[Na+].[Na+].N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1)C([O-])=O.N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C([O-])=O,"The hormones, Tand T, are tyrosine-based hormones produced by the thyroid gland. Iodine is an important component in their synthesis. The major secreted form of thyroid hormone is T. T is converted T, the more active thyroid hormone, by deiodinases in peripheral tissues. T acts in the body to increase basal metabolic rate, alter protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). Thyroid hormones are essential for proper development and differentiation of all cells of the human body. Tand Tregulate protein, fat and carbohydrate metabolism to varying extents. The most pronounced effect of the hormones is in altering how human cells use energetic compounds. The thyroid hormone derivatives bind to the thyroid hormone receptors initially to initiate their downstream effects.TargetActionsOrganismAThyroid hormone receptor alphaagonistHumansAThyroid hormone receptor betaagonistHumans",[],"['Agents used to treat hypothyroidism', 'Amino Acids', 'Amino Acids, Aromatic', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'l-Triiodothyronine', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein inducers', 'Pharmaceutical Preparations', 'Thyroid Products', 'Thyronines', 'Thyroxine-binding globulin substrates']" +DB00380,Dexrazoxane,Dexrazoxaneis a cytoprotective drug used to prevent and improve cardiomyopathy associated with doxorubicin treatment for metastatic breast cancer.,"['P11388', 'Q02880']","Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.",C[C@@H](CN1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1,"The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II.TargetActionsOrganismADNA topoisomerase -alphainhibitorHumansUDNA topoisomerase -betaNot AvailableHumans",[],"['Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Cytoprotective Agent', 'Detoxifying Agents for Antineoplastic Treatment', 'Diketopiperazines', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Immunosuppressive Agents', 'Miscellaneous Therapeutic Agents', 'Myelosuppressive Agents', 'Piperazines', 'Protective Agents', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB00261,Anagrelide,"Anagrelideis a platelet-reducing agent used to treat thrombocythemia, and its related complications, secondary to myeloproliferative neoplasms.",['Q14432'],"Anagrelide decreases platelet counts by suppressing transcription factors necessary for the synthesis and maturation of platelet-producing cells.9The drug itself appears to have a relatively short residence time in the body necessitating twice or four times daily dosing. However, given that the pharmacological effect of anagrelide therapy is reliant on a gradual suppression of platelet-producing cells, it may take 7 to 14 days11for its administration to be reflected in reduced platelet counts - for this reason any changes to anagrelide doses should not exceed 0.5 mg/day in any one week.9Evidence from animal studies suggests anagrelide may impair female fertility.9Female patients of reproductive age should be advised of the potential for adverse effects on fertility prior to initiating therapy.",ClC1=CC=C2N=C3NC(=O)CN3CC2=C1Cl,"The exact mechanism by which anagrelide lowers platelet count is unclear. Evidence from human trials suggests a dose-related suppression of megakaryocyte maturation, the cells responsible for platelet production - blood drawn from patients receiving anagrelide showed a disruption to the post-mitotic phase of megakaryocyte development and a subsequent reduction in their size and ploidy.This may be achieved via indirect suppression of certain transcription factors required for megakaryocytopoeisis, including GATA- and FOG-.Anagrelide is a known inhibitor of phosphodiesterase A (PDEA), although its platelet-lowering effects appear unrelated to this inhibition.While PDE inhibitors, as a class, can inhibit platelet aggregation, this effect is only seen at higher anagrelide doses (i.e. greater than those required to reduce platelet count).Modulation of PDEA has been implicated in causing cell cycle arrest and apoptosis in cancer cells expressing both PDEA and SLFN,and may be of value in the treatment of gastrointestinal stromal tumours.TargetActionsOrganismAcGMP-inhibited ','-cyclic phosphodiesterase AinhibitorHumans",[],"['Agents producing tachycardia', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Antiplatelet agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (weak)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Decreased Platelet Production', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Narrow Therapeutic Index Drugs', 'Phosphodiesterase 3 Inhibitors', 'Phosphodiesterase Inhibitors', 'Platelet-reducing Agents', 'QTc Prolonging Agents', 'Thrombocytosis']" +DB04883,Darusentan,Darusentan is a selective endothelin ETA receptor antagonist. It is being evaluated as a treatment for congestive heart failure and hypertension.,['P25101'],Darusentan is a selective endothelin ETA receptor antagonist.,COC1=CC(OC)=NC(O[C@H](C(O)=O)C(OC)(C2=CC=CC=C2)C2=CC=CC=C2)=N1,"The mode of action by which the endothelin receptor antagonists cause a decrease of the BP is not yet totally elucidated; however, peripheral vasodilatation due to blockade of the vasoconstrictor effects of endothelin is the most likely explanation. A reduction of cardiac contractility is considered unlikely. Several studies have been published that investigated the effects of either selective or nonselective endothelin receptor blockade in patients with heart failure. In these studies, application of endothelin antagonists, while decreasing both systemic and pulmonary BP increased cardiac index and did not alter cardiac contractility or heart rate.TargetActionsOrganismUEndothelin- receptorNot AvailableHumans",[],"['Acids, Carbocyclic', 'Endothelin Receptor Antagonists']" +DB14639,Boldenone undecylenate,Not Available,['P10275'],"The activity of boldenone is mainly anabolic, with a low androgenic potency. The drug is commonly used in doping within bodybuilding, even though this use is illegal. If intended to assist in bodybuilding, the drug is taken as part of a steroid stack of other anabolic steroids, usually with a potent androgen like testosterone as the 'base' of the stack. Boldenone is an androgen that differs from 17b-testosterone (17b-T) by only one double bond at the 1-position, and the removal of the methyl group protecting the 17-OH group allows it to be orally active.",C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)C=C[C@]34C)[C@@H]1CC[C@@H]2OC(=O)CCCCCCCCC=C,"Boldenone is a steroid hormone which has androgenic activity. Androgens bind to the androgen receptor, which regulates gene transcription.TargetActionsOrganismAAndrogen receptorNot AvailableHumans",[],"['Androstanes', 'Androstenes', 'Androstenols', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Steroids']" +DB12371,Siponimod,Siponimodis a medication used to treat relapsing multiple sclerosis.,"['Q9H228', 'P21453']","Immune system effectsSiponimod causes a dose-dependent decrease of the peripheral blood lymphocyte count within 6 hours of the first dose, caused by the reversible accumulation of lymphocytes in lymphoid tissues, due to lack of lymphocyte releaseLabel. This results in a decrease in the inflammation that is involved in multiple sclerosis. Lymphocyte counts return to normal in 90% of patients within 10 days after the cessation of therapyLabel.Effects on heart rate and rhythmSiponimod causes a temporary decrease in heart rate and atrioventricular conduction upon beginning treatment. The maximum fall in heart rate is observed in the first 6 hours post ingestion. Autonomic heart responses, including diurnal variation of heart rate and response to exercise activities, are not altered by siponimod treatmentLabel.Effects on pulmonary functionDose-dependent decreases in absolute forced expiratory volume over a time frame of 1 second were noted in siponimod-treated patients and were higher than in patients taking placeboLabel.",CCC1=CC(=CC=C1CN1CC(C1)C(O)=O)C(\C)=N\OCC1=CC=C(C2CCCCC2)C(=C1)C(F)(F)F,"Inflammation of the white and gray matter tissues in the central nervous system caused by localized immune cell infiltration and their cytokines are the initial cause of damage in MS. B lymphocytes and their cytokines are other factors in the pathogenesis of MS. Lymphotoxin [or transforming growth factor beta (TGF-β)] and TNF-α produced by these cells encourage inflammation. The SP receptor is an important receptor related to the function of lymphocytes and can be found in the central nervous system. SP receptor (SPR) signaling is associated with a wide variety of physiological processes for lymphocytes, including their egress and recirculation,.Siponimod is classified as a sphingosine--phosphate (SP) receptor modulator. Siponimod binds with high affinity to both SP receptors and . This drug blocks the ability of lymphocytes to release from the lymph nodes, decreasing the number of lymphocytes found in the peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is not known at this time, but may involve the abovementioned decrease of lymphocytes into the central nervous system, decreasing the inflammatory effects of MSLabel.TargetActionsOrganismUSphingosine -phosphate receptor modulatorHumansUSphingosine -phosphate receptor Not AvailableHumans",[],"['Agents that produce hypertension', 'Antineoplastic and Immunomodulating Agents', 'Azetines', 'Benzene Derivatives', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Immunologic Factors', 'Immunomodulatory Agents', 'Immunosuppressive Agents', 'Immunotherapy', 'Narrow Therapeutic Index Drugs', 'Receptors, Lysosphingolipid, antagonists & inhibitors', 'Selective Immunosuppressants', 'Sphingosine 1 Phosphate Receptor Modulators', 'Sphingosine 1-phosphate Receptor Modulator']" +DB01280,Nelarabine,Nelarabineis a purine nucleoside analog and antineoplastic agent used for the treatment of with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma with inadequate clinical response to prior chemotherapeutic treatments.,"['P09884', 'P18858', 'P49642', 'P23921']","Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G.14Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP).14Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent.14Since T lymphoblasts have a higher expression of deoxycytidine kinase, ara-G preferentially accumulates in T cells over B cells, thus showing higher toxicity to T lymphoblasts.1,4",COC1=NC(N)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O,"Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. As a nucleoside analog, Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA.,,,Due to its intact '-OH group, ara-GTP can be incorporated into the growing DNA strand without absolute chain termination.Despite that, the inclusion of ara-GTP into DNA strand can impair proper DNA repair processes, although the exact mechanism is not well understood, leading to inhibition of DNA elongation, apoptosis, and cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.,,,TargetActionsOrganismADNAincorporation into and destabilizationHumansADNA polymerase alpha catalytic subunitinhibitorHumansADNA ligase inhibitorHumansADNA primase small subunitinhibitorHumansARibonucleoside-diphosphate reductase large subunitinhibitorHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Immunosuppressive Agents', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'Purine Analogues']" +DB06695,Dabigatran etexilate,Dabigatran etexilateis an anticoagulant used for the prevention of venous thromboembolic events or stroke in patients with recent elective hip or knee replacement surgery and atrial fibrillation.,['P00734'],"Dabigatran etexilate is a double prodrug that is hydrolyzed to the activedabigatranby intestinal and hepatic carboxylesterases.12,13,14Dabigatran is a reversible competitive thrombin inhibitor that directly inhibits the conversion by thrombin of fibrinogen to fibrin, impairing the clotting process and acting as an anticoagulant.4,7,8,18,19Dabigatran use prolongs coagulation markers such as the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT), and dilute thrombin time (dTT), but not the international normalized ratio (INR), which cannot be used in this context as it can inwarfarinmonitoring.18,19As with all anticoagulant therapies, dabigatran carries a risk of bleeding, which may increase with concomitant use of antiplatelet agents, fibrinolytic therapy, heparins, or chronic NSAID use, and should be monitored for. Premature discontinuation of dabigatran, in the absence of an alternative anticoagulant, also carries an increased risk of thromboembolic events. Due to the risk of an epidural or spinal hematoma, dabigatran should generally not be used in the context of neuraxial anesthesia or spinal puncture; if such use is unavoidable, careful monitoring should be employed. Dabigatran should not be used in patients with prosthetic heart valves due to an increased occurrence of major bleeding and thromboembolic events. Dabigatran is a substrate of the P-gp transporter and should generally not be administered together with P-gp inhibitors or inducers, especially in patients with impaired renal function. Lastly, dabigatran or any other direct-acting oral anticoagulant should not be administered in patients with triple-positive antiphospholipid syndrome (APS) due to an increased risk of recurrent thrombotic events. In case of the need for emergency reversal,idarucizumabis available for use in adult patients; the safety and efficacy ofidarucizumabhas not been established in pediatric patients yet, for whom reversal may be achieved through hemodialysis, prothrombin complex concentrates, or recombinant FVIIa. However, none of these have been sufficiently evaluated in clinical trials.18,19",CCCCCCOC(=O)\N=C(\N)C1=CC=C(NCC2=NC3=C(C=CC(=C3)C(=O)N(CCC(=O)OCC)C3=NC=CC=C3)N2C)C=C1,"Hemostasis is a complex process that balances coagulation to prevent excessive thrombus formation or excessive bleeding. Central to the coagulation process is the serine protease thrombin (FIIa), which is synthesized as inactive prothrombin (FII) and subsequently activated by FXa/FVa, leading to a positive feedback loop and the production of large quantities of thrombin; once enough thrombin is formed, it cleaves soluble fibrinogen to form insoluble fibrin fibres that, together with aggregated platelets, form a clot. Although beneficial in wound healing, aberrant thrombus formation can lead to serious health consequences.Dabigatran is a univalent reversible direct thrombin inhibitor (DTI) that competitively inhibits thrombin with a Kiof . ± . nmol/L.,,,Furthermore, the reversible nature of the inhibition is believed to allow for some normal physiological thrombin function, which may help alleviate some adverse effects associated with anticoagulation therapy.In addition, dabigatran has several glucuronidated metabolites, all of which have been shown to possessin vitroactivity similar to the parent compound.In addition to a direct effect on thrombin activity, dabigatran has also been shown to inhibit platelet aggregation, another step in the coagulation pathway. However, the mechanism remains unclear as dabigatran inhibits platelet aggregation stimulated by thrombin and von Willebrand factor (vWF), but not by other pathways such as ADP- or thromboxane A-induced aggregation.,,,,TargetActionsOrganismAProthrombininhibitorHumans",[],"['Anticoagulants', 'Antithrombins', 'Benzimidazoles', 'Blood and Blood Forming Organs', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Hematologic Agents', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Pyridines', 'Serine Protease Inhibitors', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB09075,Edoxaban,Edoxabanis a novel oral anticoagulant used for reducing the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF).,['P00742'],"Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio).",CN(C)C(=O)[C@H]1CC[C@H](NC(=O)C(=O)NC2=NC=C(Cl)C=C2)[C@@H](C1)NC(=O)C1=NC2=C(CN(C)CC2)S1,"Edoxaban is a selective inhibitor of factor Xa, a serine endopeptidase of the clotting cascade required for cleavage of prothrombin into thrombin.TargetActionsOrganismACoagulation factor XinhibitorHumans",[],"['Anticoagulants', 'Antithrombins', 'Blood and Blood Forming Organs', 'Direct factor Xa inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Factor Xa Inhibitors', 'Hematologic Agents', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Serine Protease Inhibitors', 'Sulfur Compounds']" +DB06689,Ethanolamine oleate,Ethanolamine oleateis a mild sclerosing agent used in the treatment of esophageal varices with recent bleeding episodes.,['P00748'],"When injected intravenously, ethanolamine oleate acts primarily by irritation of the intimal endothelium of the vein and produces a sterile dose-related inflammatory response. This results in fibrosis and possible occlusion of the vein. Ethanolamine oleate also rapidly diffuses through the venous wall and produces a dose-related extravascular inflammatory reaction.",NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O,"The oleic acid component of ethanolamine oleate is responsible for the inflammatory response, and may also activate coagulation in vivo by release of tissue factor and activation of Hageman factor. The ethanolamine component, however, may inhibit fibrin clot formation by chelating calcium, so that a procoagulant action of ethanolamine oleate has not been demonstrated.TargetActionsOrganismUCalcium ionschelatorHumansUCoagulation factor XIIactivatorHumans",[],"['Antivaricose Therapy', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Fatty Acids', 'Fatty Acids, Monounsaturated', 'Fatty Acids, Unsaturated', 'Lipids', 'Pharmaceutical Preparations', 'Pharmaceutical Solutions', 'Sclerosing Agents for Local Injection', 'Sclerosing Solutions', 'Solutions', 'Vasoprotectives']" +DB01282,Carbetocin,Carbetocinis an oxytocin agent used to control postpartum hemorrhage and bleeding after giving birth.,['P30559'],"Carbetocin is a drug used to control postpartum hemorrhage, bleeding after giving birth. It is sold under the trade name Duratocin. It is an analogue of oxytocin, and its action is similar to that of oxytocin; it causes contraction of the uterus.",[H][C@]1(NC(=O)[C@H](CC2=CC=C(OC)C=C2)NC(=O)CCCSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)[C@@H](C)CC,"Carbetocin binds to oxytocin receptors present on the smooth musculature of the uterus, resulting in rhythmic contractions of the uterus, increased frequency of existing contractions, and increased uterine tone. The oxytocin receptor content of the uterus is very low in the non-pregnant state, and increases during pregnancy, reaching a peak at the time of delivery.TargetActionsOrganismAOxytocin receptoragonistHumans",[],"['Amino Acids, Peptides, and Proteins', 'Delayed-Action Preparations', 'Drug Delivery Systems', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypotensive Agents', 'Oxytocin and Analogues', 'Peptide Hormones', 'Peptides', 'Pharmaceutical Preparations', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormones', 'Pituitary Hormones, Posterior', 'Posterior Pituitary Lobe Hormones', 'Reproductive Control Agents', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Uterotonic agents']" +DB13174,Rhein,"Rhein is an anthraquinone metabolite of rheinanthrone and senna glycoside is present in many medicinal plants including Rheum palmatum, Cassia tora, Polygonum multiflorum, and Aloe barbadensis1. It is known to have hepatoprotective, nephroprotective, anti-cancer, anti-inflammatory, and several other protective effects.","['Q13133', 'P55055', 'P09917']","*Liver: *Reverses animal models of non-alcoholic fatty liver disease by lowering liver lipids and reducing inflammation5. Also reverses and prevents fibrosis in liver injury6.*Kidney: *Protects against fibrosis in nephropathy models and improves epithelial tight junction function79.Bone and joint:Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity192021.Lipid lowering and anti-obesity:Reduces body weight and fat content, and lowers high density lipoprotein and low density lipoprotein14. May prevent adipocyte differentiation13.Anti-oxidant/Pro-oxidant: Reduces levels of reactive oxygen species (ROS) at concentrations of about 2-16 microM but induces the generation of ROS at concentrations of 50 microM and above1516.Anti-cancer:Rhein has been observed to produce DNA damage and suppress DNA repair in cancer cells22. It induces apoptosis via ER stress, calcium, and mitochondria mediated pathways23. Rhein also prevents cancer cell invasion into systemic circulation by preventing angiogenesis and breakdown of the extracellular matrix24. Finally, rhein suppresses the activation of several tumor promoting signalling pathways242526.*Anti-inflammatory: *Suppresses the production of pro-inflammatory cytokines such as interleukin-1beta and interleukin-61920.*Anti-diabetic: *Lowers plasma glucose and increases survival of islet beta cells in type 2 diabetes mellitus models2.Anti-microbial:Inhibits arylamine N-acteyltransferase and cell growth in Helicobacter pylori11. Rhien also appears to be effective against many genotypes of Staphylococcus aureus12.Anti-allergenic:Inhibits production of leukotrienes and the release of histamine from mast cells17.",OC(=O)C1=CC2=C(C(O)=C1)C(=O)C1=C(C=CC=C1O)C2=O,"*Liver: *The reversal of non-alcoholic fatty liver disease stems from rhien's lipid lowering and anti-obesity actions which result in an overall decrease in body weight, high density lipoprotein, and low density lipoprotein as well as its anti-inflammatory action. The reversal of hepatic fibrosis is thought to be due to rhien's anti-inflammatory and anti-oxidant action which suppresses the pro-fibrotic signalling from macrophages and further damage from reactive oxygen species respectively. Ultimately this results in reduced expression of alpha-smooth muscle actin (Alpha-SMA) which is indicative of decreased hepatic stellate cell and myofibroblast activation. Rhein also appears to suppress the expression of transforming growth factor-Beta (TGF-Beta)*Kidney: *The protection from fibrosis in the kidney also appears to stem from rhien's anti-inflammatory action resulting in less inflammatory cell infiltration along with suppression of alpha-SMA and fibronectin expression. These indicate a reduction in the activation of interstitial fibroblasts which are responsible for excess production of extracellular matrix components. Rhien may also suppress TGF-beta expression in the kidney. The anti-fibrotic mechanism of rhien may involve the upregulation of bone morphogenetic protein and hepatic growth factor. In diabetic nephropathy rhein appears to suppress the expression of integrin-linked kinase leading to a reduction in the matrix metalloproteinase-/tissue inhibitor of matrix metalloproteinase- ratio. The improvement of epithelial tight junction function seems to involve upregulation of zona occludins protein- and occludin expression.Bone and joint:Rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)- and - as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs. The anti-inflammatory action of rhein reduces the level of interleukin-beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism.*Lipid lowering and anti-obesity: *Rhein is known to bind and inhibit liver X receptor alpha and beta with Kd values of . microM and . microM respectively. This decreases the expression of genes such as that of sterol regulatory element binding transcription factor (SREBPc) and its downstream genes for fatty acid synthase (FAS), steroyl-coenzyme A desaturase (SCD), and acetyl CoA carboxylase (ACC). SREBPc, FAS, SCD, and ACC are all involved in adipogenesis and their suppression results in less fat content. The genes for ABCA and ABCG are also suppressed. These correspond to cholesterol efflux trasporters and likely explain the reductiion in HDL and LDL seen with rhein. The inhibition of LXR by rhien relieves the inhibition on uncoupling protein expression in brown adipose tissue. The result of this is increased thermogenesis which likely plays a role in the reduction of body weight produced by rhien. Additionally, rhein may downregulate peroxisome proliferator-receptor gamma and its downstream genes to inhibit adipocyte differentiation.Anti-oxidant/Pro-oxidant:The antoxidant mechanism is unknown. The pro-oxidant action of rhien may involve the inhibition of mitochondrial respiratory complex and subsequent facilitation of NADH and NADPH dependent lipid peroxidation.Anti-cancer:The exact mechanism of rhein's ability to damage DNA and supress the expression of DNA repair enzymes ADR and MGMT is unknown. The mechanism through which rhien induces ER stress is unknown but likely involves its pro-oxidant properties. Rhein has been observed to produce increases in cytosolic calcium, reductions in mitochondrial membrane potential, and upregulation of pro-apoptotic proteins as well as leakage of cytochrome C which would induce apoptosis via the intrinsic pathway. The reduction of matrix metalloproteinase- serves to prevent extra cellular matrix breakdown by cancer cells and hinders their invasion into surrounding tissue. Rhein also decreases vascular endothelial growth factor expression through an unknown mechanism to prevent cancer cells from stimulating agiogenesis. Rhein reduces the activity of the nuclear factor kappa (NFkappaB) pathway by preventing the destruction of IKBalpha. The activity of the phosphoinositol -kinase/Akt pathway is also reduced by rhien. Rhein's inhibition of the mitogen-activated protein kinase pathways (particularly those involving extracellular signal regulated kinase) appears to follow a U-shaped dose response curve. ERK phosphorylation is inhibited at low concentrations of around microM but activated at higher concentrations of around microM. Furthermore, ERK phosporylation is again inhibited at extremely high concentrations in excess of microM. The suppression of these three pathways is likely involved in the anti-proliferative effects of rhein.Anti-inflammatory:The mechanism of rhein's anti-inflammatory effect likely involves its inhibition of the NFkappa B pathway which plays a role in the production of many pro-inflammatory cytokines. Rhein's anti-oxidant activity may also play a role in preventing damage during inflammation.Anti-diabetic:Rhein is thought to increase islet beta cell survival by suppressing the expression of dynamin-related protein and thereby preventing mitochondrial fission. Rhein's anti-oxidant properties are also thought to play a role in protecting islet beta cells. The reduction in plasma glucose is likely due to increased survival of islet beta cells and subsequent increases in insulin secretion. Rhein's anti-inflammatory action may also serve to reduce insulin resistance.Anti-microbial:Rhien inhibits H. pylori arylamine N-acetyltransferase in a dose dependent manner. The mechanism of rhein's anti-microbial effect on H. pylori and S. aureus are unknown.Anti-allergenic:Rhien inhibits -lipoxygenase with an IC of .microM. Rhien also inhibits mast cell degranulation although the specific mechanism is unknown.TargetActionsOrganismUOxysterols receptor LXR-alphainhibitorHumansUOxysterols receptor LXR-betainhibitorHumansUArylamine N-acetyltransferaseinhibitorHelicobacter pyloriUArachidonate -lipoxygenaseinhibitorHumans",[],"['Anthracenes', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'NADH, NADPH Oxidoreductases, antagonists & inhibitors', 'Quinones']" +DB00569,Fondaparinux,"Fondaparinuxis an anticoagulant used to prevent venous thromboembolism, to treat deep vein thrombosis, and to improve survival following myocardial infarction.","['P00742', 'P01008']","Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%)1,2. At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment.",CO[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]2O[C@H]([C@@H](O[C@H]3O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]4O[C@@H]([C@@H](O[C@H]5O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H]5NS(O)(=O)=O)[C@H](O)[C@H]4O)C(O)=O)[C@H](OS(O)(=O)=O)[C@H]3NS(O)(=O)=O)[C@H](O)[C@H]2OS(O)(=O)=O)C(O)=O)[C@H](O)[C@H]1NS(O)(=O)=O,"The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure. As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients,,. However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux,.TargetActionsOrganismACoagulation factor XinhibitorHumansAAntithrombin-IIIpotentiatorHumans",[],"['Anticoagulants', 'Antithrombins', 'Blood and Blood Forming Organs', 'Carbohydrates', 'Cardiovascular Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Factor Xa Inhibitors', 'Fibrin Modulating Agents', 'Hematologic Agents', 'Indirect factor Xa inhibitors', 'Miscellaneous Anticoagulants', 'Oligosaccharides', 'Polysaccharides', 'Protease Inhibitors', 'Serine Protease Inhibitors']" +DB00644,Gonadorelin,Gonadorelinis a synthetic GnRH used to test the function of gonadotropes and the pituitary.,"['P30968', 'Q96P88']","Gonadorelin is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pitutitary. In the pituitary GnRH stimulates synthesis and release of FSH and LH, a process that is controlled by the frequency and amplitude of GnRH pulses, as well as the feedback of androgens and estrogens. The pulsatility of GnRH secretion has been seen in all vertebrates, and it is necessary to ensure a correct reproductive function. Thus a single hormone, GnRH, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male. Its short half life requires infusion pumps for its clinical use",CC(C)CC(NC(=O)CNC(=O)C(CC1=CC=C(O)C=C1)NC(=O)C(CO)NC(=O)C(CC1=CNC2=CC=CC=C12)NC(=O)C(CC1=CN=CN1)NC(=O)C1CCC(=O)N1)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(=O)NCC(N)=O,"Systemic - Like naturally occurring gonadotropin-releasing hormone (GnRH), gonadorelin primarily stimulates the synthesis and release of luteinizing hormone (LH) from the anterior pituitary gland. Follicle-stimulating hormone (FSH) production and release is also increased by gonadorelin, but to a lesser degree. In prepubertal females and some gonadal function disorders, the FSH response may be greater than the LH response. For the treatment of amenorrhea, delayed puberty, and infertility the administration of gonadorelin is used to simulate the physiologic release of GnRH from the hypothalamus in treatment of delayed puberty, treatment of infertility caused by hypogonadotropic hypogonadism, and induction of ovulation in those women with hypothalamic amenorrhea. This results in increased levels of pituitary gonadotropins LH and FSH, which subsequently stimulate the gonads to produce reproductive steroids.TargetActionsOrganismAGonadotropin-releasing hormone receptoragonistHumansAPutative gonadotropin-releasing hormone II receptoragonistHumans",['Ovulation induction therapy'],"['Adrenal Cortex Hormones', 'Amino Acids, Peptides, and Proteins', 'Diagnostic Agents', 'Gonadotropin-releasing hormone agonist', 'Gonadotropin-Releasing Hormone, agonists', 'Gonadotropin-Releasing Hormone, antagonists & inhibitors', 'Gonadotropins and Antigonadotropins', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypothalamic Hormones', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Function', 'Pituitary Hormone-Releasing Hormones', 'Proteins', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Tests for Fertility Disturbances']" +DB00299,Penciclovir,Pencicloviris a topical nucleoside polymerase inhibitor used in the treatment of recurrent herpes labialis.,"['P04293', 'P06478']",Penciclovir is the active metabolite of the oral product famciclovir. The more favorable results observed with topical penciclovir versus topical acyclovir for the treatment of herpes labialis may be due to the longer intracellular half-life of penciclovir in HSV-infected cells. The activated drug inhibits the viral DNA polymerase. This impairs the ability of the virus to replicate within the cell.,NC1=NC(=O)C2=C(N1)N(CCC(CO)CO)C=N2,"Penciclovir hasin vitroactivity against herpes simplex virus types (HSV-) and (HSV-). In cells infected with HSV- or HSV-, viral thymidine kinase phosphorylates penciclovir to a monophosphate form. The monophosphate form of the drug is then converted to penciclovir triphosphate by cellular kinases. The intracellular triphosphate of penciclovir is retainedin vitroinside HSV-infected cells for - hours, compared with .- hour for acyclovir.in vitrostudies show that penciclovir triphosphate selectively inhibits viral DNA polymerase by competing with deoxyguanosine triphosphate. Inhibition of DNA synthesis of virus-infected cells inhibits viral replication. In cells not infected with HSV, DNA synthesis is unaltered. Resistant mutants of HSV can occur from qualitative changes in viral thymidine kinase or DNA polymerase. The most commonly encountered acyclovir-resistant mutants that are deficient in viral thymidine kinase are also resistant to penciclovir.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-AThymidine kinaseinducer",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Direct Acting Antivirals', 'Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acid Synthesis Inhibitors', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'Purines', 'Purinones', 'Reverse Transcriptase Inhibitors']" +DB09102,Daclatasvir,Daclatasviris a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.,['Q5L478'],Daclatasvir is a direct-acting antiviral agent that targets the NS5A and causes a decrease in serum HCV RNA levels. It disrupts HCV replication by specifically inhibiting the critical functions of an NS5A protein in the replication complex3. It is shown to cause downregulation of the hyperphosphorylation of NS5A. It does not appear to prolong the QT interval even when given at 3 times the maximum recommended dose.,COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(N1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CN=C(N1)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)OC)C(C)C,NSA is a viral nonstructural phospoprotein that is part of a functional replication complex in charge of viral RNA genome amplification on endoplasmic reticulum membranes. It has the ability to bind to HCV RNA. It is shown to have two distinct functions in HCV RNA replication based on phosphorylated states. Maintaining the HCV replication complex is mediated by the cis-acting function of basally phosphorylated NSA and the trans-acting function of hyperphosphorylated NSA modulates HCV assembly and infectious particle formation. Daclatasvir is shown to disrupt hyperphosphorylated NSA proteins thus interfere with the function of new HCV replication complexes. It is also reported that daclatasvir also blocks both intracellular viral RNA synthesis and virion assembly/secretion in vivo.TargetActionsOrganismANonstructural protein AinhibitorHepatitis C Virus,[],"['Acids, Acyclic', 'Amino Acids', 'Amino Acids, Branched-Chain', 'Amino Acids, Essential', 'Amino Acids, Peptides, and Proteins', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'HCV Replication Complex Inhibitors', 'Hepatitis C Virus NS5A Inhibitor', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B3 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates']" +DB09296,Ombitasvir,Ombitasviris a direct acting antiviral agent used in combination with other antiviral agents for the treatment of Hepatitis C Virus (HCV) infections.,['Q5L478'],Ombitasvir is classified as a direct acting antiviral and acts against HCV to inhibit viral replicationLabel.,COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C(C=C1)[C@@H]1CC[C@H](N1C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)OC)C(C)C)C=C1,"Ombitasvir is an inhibitor of the HCV non-structural protein A. While the precise role of this protein is unknown, it is essential to viral replication and virion assemblyLabel. Potential modes of action of NSA inhibitors like Elbasvir include blocking signaling interactions, redistribution of NSA from the endoplasmic reticulum to the surface of lipid droplets, and modification of the HCV replication complex.TargetActionsOrganismANonstructural protein AinhibitorHepatitis C Virus",[],"['Amides', 'Amines', 'Amino Acids', 'Amino Acids, Branched-Chain', 'Amino Acids, Cyclic', 'Amino Acids, Essential', 'Amino Acids, Peptides, and Proteins', 'Aniline Compounds', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Hepatitis C Virus NS5A Inhibitor', 'Imino Acids', 'P-glycoprotein substrates', 'Treatments for Hepatitis C', 'UGT1A1 Inhibitors']" +DB09183,Dasabuvir,Dasabuviris a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.,['P87764'],Dasabuvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1Label.,COC1=C(C=C(C=C1C1=CC2=CC=C(NS(C)(=O)=O)C=C2C=C1)N1C=CC(=O)NC1=O)C(C)(C)C,"Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NSB gene, which is essential for replication of the viral genomeLabel. Based on drug resistance mapping studies of HCV genotypes a and b, dasabuvir targets the palm domain of the NSB polymerase, and is therefore referred to as a non-nucleoside NSB-palm polymerase inhibitor. The EC values of dasabuvir against genotype a-H and b-Con strains in HCV replicon cell culture assays were . nM and . nM, respectively.By binding to NSb outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome,Label. A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Dasabuvir is therefore limited to treating genotypes a and b, and must be used in combination with other antiviral products.TargetActionsOrganismANonstructural protein B (NSB)inhibitor",[],"['Amides', 'Amines', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Hepatitis C Virus Non-Nucleoside NS5B Palm Polymerase Inhibitor', 'Naphthalenes', 'P-glycoprotein substrates', 'Pyrimidines', 'Pyrimidinones', 'RNA Replicase Inhibitors', 'Sulfones', 'Sulfur Compounds', 'Treatments for Hepatitis C', 'UGT1A1 Inhibitors']" +DB09297,Paritaprevir,Paritapreviris a direct acting antiviral agent used in combination with other antiviral agents for the treatment of Hepatitis C Virus (HCV) infections.,['B0B3C9'],"At concentrations approximately 6 and 1.8 times the therapeutic concentrations of paritaprevir and ombitasvir, the combination did not prolong QTc to any clinically relevant extentLabel.",[H][C@@]12C[C@]1(NC(=O)[C@]1([H])C[C@H](CN1C(=O)[C@H](CCCCC\C=C/2)NC(=O)C1=CN=C(C)C=N1)OC1=NC2=C(C=CC=C2)C2=C1C=CC=C2)C(=O)NS(=O)(=O)C1CC1,"Paritaprevir is a potent inhibitor of the NS/A serine protease of Hepatitis C Virus (HCV)Label. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein (NS) and its activating cofactor Nonstructural Protein A (NSA) are responsible for cleaving it into the following structural and nonstructural proteins required for assembly into mature virus: NS, NSA, NSB, NSA, and NSB. By inhibiting viral protease NS/A, paritaprevir therefore prevents viral replication and function.TargetActionsOrganismANS/A proteininhibitorHepatitis C Virus",[],"['Amides', 'Amino Acids', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Inhibitors', 'Cycloparaffins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'HCV NS3/4A Protease Inhibitors', 'Imino Acids', 'Lactams', 'NS3/4A Protease Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 inhibitors', 'OATP1B3 substrates', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B3 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Sulfones', 'Sulfur Compounds', 'Treatments for Hepatitis C', 'UGT1A1 Inhibitors']" +DB06290,Simeprevir,Simepreviris a direct-acting antiviral agent that inhibits HCV NS3/4A protease to treat chronic hepatitis C virus (HCV) infection in adults with HCV genotype 1 or 4.,"['Q91RS4', 'B0B3C9']","Simeprevir is a direct-acting antiviral agent and inhibitor for HCV NS3/4A protease, which is an important enzyme required for viral replication. UnlikeBoceprevirandTelaprevir, simeprevir is a competitive, reversible, macrocyclic, noncovalent inhibitor. The macromolecular cyclic portion of the molecule improves the affnity and selectivity characteristics, which allows rapid association and slow dissociation to the protein target through noncovalent binding3.",[H][C@]12C[C@]1(NC(=O)[C@]1([H])C[C@H](C[C@@]1([H])C(=O)N(C)CCCC\C=C/2)OC1=CC(=NC2=C1C=CC(OC)=C2C)C1=NC(=CS1)C(C)C)C(=O)NS(=O)(=O)C1CC1,"Simeprevir is accumulated in the liver after uptake into hepatocytes via OATPB/. NS/A heterodimeric complex is composed of the cofactor NA subunit and N subunit which contains the proteolytic site. The NS/A protease cleaves the HCV polyprotein downstream of the NS site, generating non-structural viral proteins NS, NSA, NSB, NSA and NSB and subsequently formation of mature proteins,. Simeprevir exerts an inhibitory action on HCV polyprotein cleavage via induced-fit binding to an extended S subsite located in the NS catalytic site. NS/A inhibitors usually depend on few interactions located in the substrate binding groove of the viral serine protease, thus are susceptible to resistance and failed treatment from few critical mutations in these sites. +At higher concentration above their antiviral half-maximal effective concentration (EC), simeprevir and other NS/A inhibitors also restore interferon (IFN)-signaling pathways that are thought to be disrupted by NS/A protease and recover innate immune processes. NS/A protease cleaves two essential adaptor proteins that initiate signaling leading to activation of IFN regulatory factor and IFN-α/β synthesis, which are mitochondrial antiviral-signaling proteins (MAVS otherwise known as IPS-, VISA, or Cardif) and toll/interleukin- receptor (TIR)- domain-containing adaptor-inducing IFN-β (TRIF). Blocking the function of these adaptor proteins results in impaired interferon induction. NS/A inhibitors recover the proper IFN-signaling pathways,.TargetActionsOrganismANS proteaseinhibitorHepatitis C VirusANS/A proteininhibitorHepatitis C Virus",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'BSEP/ABCB11 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'HCV NS3/4A Protease Inhibitors', 'HCV Protease Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'NS3/4A Protease Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 inhibitors', 'OATP1B3 substrates', 'OATP2B1/SLCO2B1 substrates', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B3 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Protease Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB09027,Ledipasvir,Ledipasviris a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.,['Q5L478'],"Ledipasvir acts against HCV and is categorized as a direct-acting antiviral agent (DAA).At a dose of 120 mg twice daily (2.67 times the maximum recommended dosage), ledipasvir does not prolong QTc interval to any clinically relevant extentLabel.",COC(=O)N[C@@H](C(C)C)C(=O)N1CC2(CC2)C[C@H]1C1=NC(=CN1)C1=CC=C2C3=CC=C(C=C3C(F)(F)C2=C1)C1=CC=C2NC(=NC2=C1)[C@@H]1[C@H]2CC[C@H](C2)N1C(=O)[C@@H](NC(=O)OC)C(C)C,"Ledipasvir is an inhibitor of the Hepatitis C Virus (HCV) NSA protein required for viral RNA replication and assembly of HCV virions. Although its exact mechanism of action is unknown, it is postulated to prevent hyperphosphorylation of NSA which is required for viral production.TargetActionsOrganismANonstructural protein AinhibitorHepatitis C Virus",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'BCRP/ABCG2 Inhibitors', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Hepatitis C Virus NS5A Inhibitor', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Treatments for Hepatitis C']" +DB04862,Merimepodib,"Merimepodib (VX-497) is a novel noncompetitive inhibitor of IMPDH. Merimepodib is orally bioavailable and inhibits the proliferation of primary human, mouse, rat, and dog lymphocytes at concentrations of approximately 100 nM.",['P0C0H6'],"Merimepodib, an oral drug, contains a novel inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme responsible for stimulating the production of lymphocytes. Merimepodib has the potential to exert direct antiviral activity, as well as affect the immune response by acting on lymphocyte migration and proliferation. Consequently, merimepodib may be an effective treatment for hepatitis C virus (HCV) infection, as the disease involves both viral proliferation and liver inflammation.",COC1=C(C=CC(NC(=O)NC2=CC=CC(CNC(=O)O[C@H]3CCOC3)=C2)=C1)C1=CN=CO1,"Merimepodib is a orally active inhibitor of inosine monophospate dehydrogenase (IMPDH). IMPDH inhibition leads to a reduction in intracellular guanosine triphosphate (GTP), a molecule required for DNA and RNA synthesis.TargetActionsOrganismUInosine-'-monophosphate dehydrogenaseNot AvailableStreptococcus pyogenes",[],"['Acids, Acyclic', 'Amides', 'Benzene Derivatives', 'IMP Dehydrogenase, antagonists & inhibitors']" +DB05521,Telaprevir,Telapreviris an NS3/4A viral protease inhibitor used in combination with other antivirals for the curative treatment of chronic Hepatitis C Virus infections.,"['B0B3C9', 'Q9Y6L6', 'O94956']",Telaprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1Label.,[H][C@@]12CCC[C@]1([H])[C@H](N(C2)C(=O)[C@@H](NC(=O)[C@@H](NC(=O)C1=NC=CN=C1)C1CCCCC1)C(C)(C)C)C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1,"Telaprevir is a NS/a protease inhibitor used to inhibit viral HCV replicationLabel. NS/a protease is an integral part of viral replication and mediates the cleavage the virally encoded polyprotein to mature proteins (NSA, NSB, NSA and NSB)Label. Telaprevir inhibits NS/A with an IC of nM.TargetActionsOrganismANS/A proteininhibitorHepatitis C VirusUSolute carrier organic anion transporter family member BinhibitorHumansUSolute carrier organic anion transporter family member BinhibitorHumans",[],"['Amino Acids, Peptides, and Proteins', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals for treatment of HCV infections', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'HCV NS3/4A Protease Inhibitors', 'NS3/4A Protease Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peptides', 'Protease Inhibitors']" +DB11689,Selumetinib,"Selumetinibis a MEK 1/2 inhibitor used in pediatric patients to treat neurofibromatosis type 1 (NF1) accompanied by symptomatic, inoperable plexiform neurofibromas (PN).","['Q02750', 'P36507']","Selumetinib is a non-ATP-competitive mitogen-activated protein kinase kinase 1 and 2 (MEK1 and MEK2) inhibitor.6By selectively targeting MEK1 and MEK2, selumetinib is able to inhibit oncogenic downstream effects of the Raf-MEK-ERK signaling pathway, which is often overactive in certain types of cancer.6Indeed, a study investigating the effects of selumetinib in children with NF-1 found that treatment with the anti-neoplastic resulted in reduced tumor size.3Decreases in tumor-associated pain and improvements in overall function were also subjectively reported.3Selumetinib has minimal off-target activity, contributing to its impressive safety profile.11",CN1C=NC2=C(F)C(NC3=C(Cl)C=C(Br)C=C3)=C(C=C12)C(=O)NOCCO,"The Ras-Raf-MEK-ERK signaling cascade is known to be activated in several types of cancer, and regulates the transcription of proteins involved in apoptosis.,In addition, studies have shown that mutations of the Raf component of the pathway can contribute to chemotherapy drug resistance.,Ras as well as several kinases and phosphatases are responsible for regulating the Raf-MEK-ERK pathway.Often in cancers, Ras (a G-protein coupled receptor) is deregulated, allowing downstream signalling to proceed unchecked.Through several complex steps, Raf phosphorylates and activates MEK, which then phosphorylates and activates ERK.,ERK is then able to exert its effects on several downstream targets.,As such, therapies inhibiting upstream components of this pathway have become attractive targets for cancer treatment.Selumetinib exerts its effects by selectively inhibiting MEK and MEK which can effectively blunt the pleiotropic effects of the Ras-Raf-MEK-ERK cascade.,By inhibiting this oncogenic pathway, selumetinib reduces cell proliferation, and promotes pro-apoptotic signal transduction.,,TargetActionsOrganismADual specificity mitogen-activated protein kinase kinase inhibitorHumansADual specificity mitogen-activated protein kinase kinase inhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Kinase Inhibitor', 'Mitogen-activated protein kinase (MEK) inhibitors', 'Mitogen-Activated Protein Kinase Kinase 1 Inhibitors', 'Mitogen-Activated Protein Kinase Kinase 2 Inhibitors', 'P-glycoprotein substrates', 'Protein Kinase Inhibitors', 'Tyrosine Kinase Inhibitors', 'UGT1A1 Substrates']" +DB05260,Gallium nitrate,Gallium nitrateis a drug previously indicated to treat cancer-related hypercalcemia.,"['P31350', 'P21281']","Gallium nitrate produces a hypocalcemic effect by inhibiting calcium resorption from bone, possibly blocking osteoclast activity and reducing increased bone turnover.9Preclinical studies demonstrated that gallium dose-dependently accumulates in areas of high bone turnover, where it is incorporated into hydroxyapatite, making it less susceptible to dissolution and osteoclast-mediated resorption.4,5No cytotoxic effects were observed on bone cells in drug-treated animals.9Gallium nitrate exhibits antitumour activity, which is reported to be unrelated to the physiological mechanism involved in its bone turnover effects.4Anti-inflammatory and immunosuppressant effects have also been documented.7",[Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O,"A high incidence of hypercalcemia is often observed in patients with non-small cell lung cancer, breast cancer, multiple myeloma, kidney cancer, and cancer of head and neck. Hypercalcemia of malignancy seems to result from an imbalance between the net resorption of bone and urinary excretion of calcium. Patients with extensive osteolytic bone metastases frequently develop hypercalcemia.Althoughin vitroand animal studies have been performed to investigate the mechanism of action of gallium nitrate, the precise mechanism for inhibiting calcium resorption has not been determined.Gallium, the active component that exerts the physiological effects of gallium nitrate, may induce physicochemical changes in the bone matrix to promote hydroxyapatite crystallization and attenuate mineral dissolution.,Gallium may also decrease acid secretion by osteoclastsand modulate the synthesis of osteocalcin, an osteoblast-specific bone matrix protein that triggers bone resorption.Osteoclast morphology or viability is not reported to be affected.Gallium nitrate may modulate inflammation.In vitro, it was shown to block the production of inflammatory cytokines, such as interleukin- (IL-) beta, by macrophage-like cells. Gallium nitrate also dose-dependently inhibited matrix metalloproteinase activity promoted by tissue plasminogen activator (tPA).,TargetActionsOrganismURibonucleoside-diphosphate reductase subunit MinhibitorHumansUV-type proton ATPase subunit B, brain isoforminhibitorHumans",[],"['Antineoplastic Agents', 'Bone Resorption Inhibition', 'Calcium Resorption Inhibitor', 'Calcium-Regulating Hormones and Agents', 'Elements', 'Immunosuppressive Agents', 'Metals', 'Metals, Heavy', 'Narrow Therapeutic Index Drugs']" +DB13872,Lormetazepam,Lormetazepamis a benzodiazepine indicated in the treatment of anxiety and the induction of anesthesia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Lormetazepam is a benzodiazepine which reduces central nervous system (CNS) activity2,1. It produces anxiolytic, muscle relaxant, sedative and hypnotic effects. Because it is a short-acting benzodiapine, it does not produce significant sedation after waking.",CN1C2=C(C=C(Cl)C=C2)C(=NC(O)C1=O)C1=CC=CC=C1Cl,"Lormetazepam, as a benzodiazepine, binds to the regulatory site between the α and γ subunits of γ-aminobutryic acid (GABA) A receptors with γ and α, α, α, or α subunits. This facilitates the opening of the chloride channel allowing chloride ions to flow into the neuron resulting in hyperpolarization. Hyperpolarized neurons require greater simulation to reach their action potential threshold. The general inhibitory effect on neuronal depolarization produces the effects of lormetazepam.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Benzazepines', 'Benzodiazepines and benzodiazepine derivatives', 'Benzodiazepinones', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Psycholeptics']" +DB01072,Atazanavir,Atazanaviris an antiviral protease inhibitor used in combination with other antiretrovirals for the treatment of HIV.,['Q72874'],"Atazanavir (ATV) is an azapeptide HIV-1 protease inhibitor (PI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Atazanavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Atazanivir is pharmacologically related but structurally different from other protease inhibitors and other currently available antiretrovirals.6Atazanavir exhibits anti-HIV-1 activity with a mean 50% effective concentration (EC50) in the absence of human serum of 2 to 5 nM against a variety of laboratory and clinical HIV-1 isolates grown in peripheral blood mononuclear cells, macrophages, CEM-SS cells, and MT-2 cells.10Atazanavir has activity against HIV-1 Group M subtype viruses A, B, C, D, AE, AG, F, G, and J isolates in cell culture. Atazanavir has variable activity against HIV-2 isolates (1.9-32 nM), with EC50values above the EC50values of failure isolates. Two-drug combination antiviral activity studies with atazanavir showed no antagonism in cell culture with PIs (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir), NNRTIs (delavirdine, efavirenz, and nevirapine), NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir DF, and zidovudine), the HIV-1 fusion inhibitor enfuvirtide, and two compounds used in the treatment of viral hepatitis, adefovir and ribavirin, without enhanced cytotoxicity.10HIV-1 isolates with a decreased susceptibility to atazanavir have been selected in cell culture and obtained from patients treated with atazanavir or atazanavir with ritonavir. HIV-1 isolates with 93- to 183-fold reduced susceptibility to atazanavir from three different viral strains were selected in cell culture for 5 months. The substitutions in these HIV-1 viruses that contributed to atazanavir resistance include I50L, N88S, I84V, A71V, and M46I. Changes were also observed at the protease cleavage sites following drug selection. Recombinant viruses containing the I50L substitution without other major PI substitutions were growth impaired and displayed increased susceptibility in cell culture to other PIs (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir). The I50L and I50V substitutions yielded selective resistance to atazanavir and amprenavir, respectively, and did not appear to be cross-resistant.10Concentration- and dose-dependent prolongation of the PR interval in the electrocardiogram has been observed in healthy subjects receiving atazanavir. In placebo-controlled Study AI424-076, the mean (±SD) maximum change in PR interval from the predose value was 24 (±15) msec following oral dosing with 400 mg of atazanavir (n=65) compared to 13 (±11) msec following dosing with placebo (n=67). The PR interval prolongations in this study were asymptomatic. There is limited information on the potential for a pharmacodynamic interaction in humans between atazanavir and other drugs that prolong the PR interval of the electrocardiogram.Electrocardiographic effects of atazanavir were determined in a clinical pharmacology study of 72 healthy subjects. Oral doses of 400 mg (maximum recommended dosage) and 800 mg (twice the maximum recommended dosage) were compared with placebo; there was no concentration-dependent effect of atazanavir on the QTc interval (using Fridericia’s correction). In 1793 subjects with HIV-1 infection, receiving antiretroviral regimens, QTc prolongation was comparable in the atazanavir and comparator regimens. No atazanavir-treated healthy subject or subject with HIV-1 infection in clinical trials had a QTc interval >500 msec",COC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@@H](O)CN(CC1=CC=C(C=C1)C1=CC=CC=N1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C,"Atazanavir selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV- infected cells by binding to the active site of HIV- protease, thus preventing the formation of mature virions. Atazanavir is not active against HIV-.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Amino Acids, Peptides, and Proteins', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'Nephrotoxic agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Oligopeptides', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Peptides', 'Potential QTc-Prolonging Agents', 'Protease Inhibitors', 'Pyridines', 'QTc Prolonging Agents', 'UDP Glucuronosyltransferases Inhibitors', 'UGT1A1 Inhibitors', 'Viral Protease Inhibitors']" +DB13025,Tiapride,"Tiaprideis a dopamine D2 and D3 receptor antagonist indicated in the treatment of chorea in Huntington's disease, as well as agitation and anxiety in the elderly or with acute or chronic alcoholism.","['P14416', 'P35462', 'P08908', 'P28222', 'P28221', 'P28566', 'P30939', 'P28223', 'P41595', 'P28335', 'P46098', 'O95264', 'Q8WXA8', 'Q70Z44', 'A5X5Y0', 'Q13639', 'P50406', 'P34969', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Tiapride has a high degree of regional selectivity for limbic areas. One study found that tiapride shows over three times as much affinity for limbic areas than striatal areas as opposed to the near equal selectivity for limbic and striatal regions shown by haloperidol. +Another study in rats found tiapride's affinity for the septum, a limbic region, to be over thirty times as high as for the striatum. +Efficacy at the D2 receptor is moderate, with 80 percent of receptors occupied even in the presence of excess tiapride concentrations.",CCN(CC)CCNC(=O)C1=CC(=CC=C1OC)S(C)(=O)=O,"Tiapride is a selective dopamine D and D receptor antagonist, offering an advantage over other neuroleptic drugs, such as haloperidol and risperidone, which bind a range of targets including four of the five known dopamine receptor subtypes (D-), serotonin (-HTA, C), α- and α-adrenergic, and histamine H receptors. Compared to these drugs, tiapride has a relatively moderate affinity for its target receptors, displacing percent of H-raclopride binding at a concentration of nM at D receptors and a concentration of nM at D receptors.TargetActionsOrganismADopamine D receptorblockerHumansADopamine D receptorblockerHumansASerotonin ReceptorsantagonistHumansAAlpha- adrenergic receptorsantagonistHumansAAlpha- adrenergic receptorsantagonistHumans",[],"['Acids, Carbocyclic', 'Amines', 'Antipsychotic Agents', 'Benzamides and benzamide derivatives', 'Benzene Derivatives', 'Benzoates', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Dopamine Agents', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Ethylamines', 'Nervous System', 'Neurotoxic agents', 'Neurotransmitter Agents', 'Psycholeptics', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB00701,Amprenavir,Amprenaviris a protease inhibitor used to treat HIV infection.,['Q72874'],Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.,CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1,"Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Acids, Acyclic', 'Amides', 'Amprenavir and Prodrugs', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antibiotics, Antitubercular', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Drugs for Treatment of Tuberculosis', 'Enzyme Inhibitors', 'HIV Protease Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Sulfones', 'Sulfur Compounds', 'Viral Protease Inhibitors']" +DB11093,Calcium citrate,Calcium citrateis an ingredient found in a variety of supplements and vitamins.,"['P41180', 'P27797', 'P27797', 'Q99828', 'Q99828', 'O75340', 'O75340', 'P30626', 'P30626', 'Q99653', 'Q99653', 'P09486', 'P09486', 'P27824', 'P27824', 'P35556', 'P35556', 'P04271', 'P04271', 'O14958', 'O14958', 'Q15493', 'Q15493', 'Q9UBV8', 'Q9UBV8', 'P06703', 'P06703', 'P13693', 'P13693', 'O75838', 'O75838', 'Q99584', 'Q99584', 'P31415', 'P31415', 'Q02818', 'Q02818', 'P80303', 'P80303', 'P0DP23', 'P0DP23', 'Q75N90', 'Q75N90', 'P28676', 'P28676', 'Q9ULU8', 'Q9ULU8', 'P0DP24', 'P0DP24', 'P0DP25', 'P0DP25', 'Q96FQ6', 'Q96FQ6', 'P22676', 'P22676', 'Q13938', 'Q13938', 'Q86UW7', 'Q86UW7', 'Q96L12', 'Q96L12', 'Q9ULB1', 'Q9ULB1', 'P62166', 'P62166']",Increases plasma calcium levels leading to a decrease in calcium flux and increase in calcium deposition into bone3,[Ca++].[Ca++].[Ca++].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O.OC(CC([O-])=O)(CC([O-])=O)C([O-])=O,"Calcium citrate increases plasma calcium levels. This reduces calcium flux from osteocyte activity by reducing the secretion of parathyroid hormone (PTH). Calcium does this by stimulating a G-protein coupled calcium receptor on the surface of parathyroid cells. The reduction in calcium flux increases the amount of calcium deposited in bone resulting in an increase in bone mineral density. The reduction in PTH secretion also reduces the amount of vitamin D metabolized to its active form, calcidiol. Since calcidiol increases the expression of calcium dependent ATPases and transient receptor potential cation channel subfamily V member (TRPV) both of which are involved in calcium uptake from the gut, a reduction in calcidiol results in less calcium absorption. Additionally, TRPV, the channel responsible for calcium reabsorption in the kidney, is downregulated when PTH secretion is reduced thus increasing calcium excretion via the kidneys. Another hormone, calitonin, is likely involved in the reduction of bone resorption during periods of high plasma calcium.TargetActionsOrganismAExtracellular calcium-sensing receptoragonistHumansNCalreticulinligandHumansUCalcium and integrin-binding protein ligandHumansUProgrammed cell death protein agonistHumansUSorcinligandHumansUCalcineurin B homologous protein agonistHumansNSPARCligandHumansNCalnexinligandHumansNFibrillin-ligandHumansNProtein S-BligandHumansNCalsequestrin-ligandHumansNRegucalcinligandHumansNPeflinligandHumansUProtein S-AligandHumansNTranslationally-controlled tumor proteinligandHumansUCalcium and integrin-binding family member ligandHumansNProtein S-AligandHumansNCalsequestrin-ligandHumansUNucleobindin-ligandHumansUNucleobindin-ligandHumansUCalmodulinagonistHumansUFibrillin-ligandHumansUGrancalcinligandHumansUCalcium-dependent secretion activator agonistHumansUCalmodulin-agonistHumansUCalmodulin-agonistHumansUProtein S-AligandHumansUCalretininligandHumansUCalcyphosinligandHumansUCalcium-dependent secretion activator agonistHumansUCalreticulin-ligandHumansUNeurexin-agonistHumansUNeuronal calcium sensor ligandHumans",[],"['Acids, Acyclic', 'Alimentary Tract and Metabolism', 'Biological Factors', 'Calcium Compounds', 'Calcium Salts', 'Calcium-Regulating Hormones and Agents', 'Citrates', 'Compounds used in a research, industrial, or household setting', 'Dicarboxylic Acids', 'Diet, Food, and Nutrition', 'Elements', 'Food', 'Food Additives', 'Food Ingredients', 'Hydroxy Acids', 'Metals', 'Metals, Alkaline Earth', 'Mineral Supplements', 'Physiological Phenomena', 'Polyvalent cation containing laxatives, antacids, oral supplements', 'Radioisotopes', 'Tricarboxylic Acids']" +DB01070,Dihydrotachysterol,Dihydrotachysterolis a synthetic analog of vitamin D that does not require renal activation like vitamin D2 or Vitamin D3.,['P11473'],"Dihydrotachysterol is hydroxylated in the liver to 25-hydroxydihydrotachysterol, which is the major circulating active form of the drug. It does not undergo further hydroxylation by the kidney and therefore is the analogue of 1, 25-dihydroxyvitamin D. Dihydrotachysterol is effective in the elevation of serum calcium by stimulating intestinal calcium absorption and mobilizing bone calcium in the absence of parathyroid hormone and of functioning renal tissue. Dihydrotachysterol also increases renal phosphate excretion.",CC(C)[C@@H](C)\C=C\[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1/C[C@@H](O)CC[C@@H]1C,"Once hydroxylated to -hydroxydihydrotachysterol, the modified drug binds to the vitamin D receptor. The bound form of the vitamin D receptor serves as a transcriptional regulator of bone matrix proteins, inducing the expression of osteocalcin and suppressing synthesis of type I collagen. Vitamin D (when bound to the vitamin D receptor)stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. This stimulates intestinal calcium absorption and increases renal phosphate excretion. These are functions that are normally carried out by the parathyroid hormone.TargetActionsOrganismAVitamin D receptoragonistHumans",[],"['Alimentary Tract and Metabolism', 'Bone Density Conservation Agents', 'Cholestanes', 'Cholestenes', 'Diet, Food, and Nutrition', 'Food', 'Fused-Ring Compounds', 'Lipids', 'Membrane Lipids', 'Micronutrients', 'Physiological Phenomena', 'Secosteroids', 'Steroids', 'Sterols', 'Vitamin D and Analogues', 'Vitamins', 'Vitamins (Fat Soluble)']" +DB00491,Miglitol,Miglitolis an oral alpha-glucosidase inhibitor used to improve glycemic control by delaying the digestion of carbohydrates.,"['P10253', 'Q14697', 'Q8TET4', 'O43451']","Miglitol, an oral alpha-glucosidase inhibitor, is a desoxynojirimycin derivative that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, miglitol reduce levels of glycosylated hemoglobin in patients with Type II (non-insulin-dependent) diabetes mellitus. Systemic nonenzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time. Because its mechanism of action is different, the effect of miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, miglitol diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Miglitol has minor inhibitory activity against lactase and consequently, at the recommended doses, would not be expected to induce lactose intolerance.",OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO,"In contrast to sulfonylureas, miglitol does not enhance insulin secretion. The antihyperglycemic action of miglitol results from a reversible inhibition of membrane-bound intestinal a-glucoside hydrolase enzymes. Membrane-bound intestinal a-glucosidases hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in delayed glucose absorption and lowering of postprandial hyperglycemia.TargetActionsOrganismALysosomal alpha-glucosidaseantagonistHumansANeutral alpha-glucosidase ABantagonistHumansANeutral alpha-glucosidase CantagonistHumansAMaltase-glucoamylase, intestinalantagonistinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Alkaloids', 'Blood Glucose Lowering Agents', 'Carbohydrates', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Glycoside Hydrolase Inhibitors', 'Hypoglycemia-Associated Agents', 'Imines', 'Imino Pyranoses', 'Imino Sugars', 'Oral Hypoglycemics', 'Piperidines']" +DB01090,Pentolinium,Pentolinium is a nicotinic antagonist that has been used as a ganglionic blocking agent in hypertension.,"['P32297', 'P30926', 'Q9GZZ6']","Pentolinium acts as a ganglionic blocking agent. Pentolinium inhibits release of adrenaline and noradrenaline from adrenergic nerves. It is used as an antihypertensive, and can be administered orally, intramuscularly, and subcutaneously.",C[N+]1(CCCCC[N+]2(C)CCCC2)CCCC1,"Pentolinium binds to the nicotinic (ganglion) acetylcholine receptor. This receptor/channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. Blockage of the receptor leads to smooth muscle relaxation and vasodilaton.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumansANeuronal acetylcholine receptor subunit beta-antagonistHumansANeuronal acetylcholine receptor subunit alpha-antagonistHumans",[],"['Anticholinergic Agents', 'Antihypertensive Agents', 'Autonomic Agents', 'Cardiovascular Agents', 'Cholinergic Agents', 'Ganglion Blockers', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Peripheral Nervous System Agents', 'Pyrrolidines']" +DB00119,Pyruvic acid,Pyruvic acidis an ingredient of a blood cell processing solution used to rejuvenate a unit of red blood cells (RBC) in preparation for transfusion.,"['O15427', 'P36021', 'Q9BYV1', 'O15375', 'P30613', 'O15403', 'O60669', 'P11177', 'P14618', 'P80404', 'O15374', 'O95907', 'P53985', 'P11498']","Pyruvic acid or pyruvate is a key intermediate in the glycolytic and pyruvate dehydrogenase pathways, which are involved in biological energy production. Pyruvate is widely found in living organisms. It is not an essential nutrient since it can be synthesized in the cells of the body. Certain fruits and vegetables are rich in pyruvate. For example, an average-size red apple contains approximately 450 milligrams. Dark beer and red wine are also rich sources of pyruvate. Recent research suggests that pyruvate in high concentrations may have a role in cardiovascular therapy, as an inotropic agent. Supplements of this dietary substance may also have bariatric and ergogenic applications.",CC(=O)C(O)=O,"Pyruvate serves as a biological fuel by being converted to acetyl coenzyme A, which enters the tricarboxylic acid or Krebs cycle where it is metabolized to produce ATP aerobically. Energy can also be obtained anaerobically from pyruvate via its conversion to lactate. Pyruvate injections or perfusions increase contractile function of hearts when metabolizing glucose or fatty acids. This inotropic effect is striking in hearts stunned by ischemia/reperfusion. The inotropic effect of pyruvate requires intracoronary infusion. Among possible mechanisms for this effect are increased generation of ATP and an increase in ATP phosphorylation potential. Another is activation of pyruvate dehydrogenase, promoting its own oxidation by inhibiting pyruvate dehydrogenase kinase. Pyruvate dehydrogenase is inactivated in ischemia myocardium. Yet another is reduction of cytosolic inorganic phosphate concentration. Pyruvate, as an antioxidant, is known to scavenge such reactive oxygen species as hydrogen peroxide and lipid peroxides. Indirectly, supraphysiological levels of pyruvate may increase cellular reduced glutathione.TargetActionsOrganismUMonocarboxylate transporter Not AvailableHumansUMonocarboxylate transporter Not AvailableHumansUAlanine--glyoxylate aminotransferase , mitochondrialNot AvailableHumansUMonocarboxylate transporter Not AvailableHumansUPyruvate kinase PKLRNot AvailableHumansUMonocarboxylate transporter Not AvailableHumansUMonocarboxylate transporter Not AvailableHumansUPyruvate dehydrogenase E component subunit beta, mitochondrialNot AvailableHumansUPyruvate kinase PKMNot AvailableHumansU-aminobutyrate aminotransferase, mitochondrialinhibitorHumansUMonocarboxylate transporter Not AvailableHumansUMonocarboxylate transporter Not AvailableHumansUMonocarboxylate transporter Not AvailableHumansUPyruvate carboxylase, mitochondrialNot AvailableHumans",['Red blood cell rejuvination therapy'],"['Dietary Supplements', 'Keto Acids', 'Pyruvates', 'Supplements']" +DB01620,Pheniramine,Pheniramineis an antihistamine used to treat allergic rhinitis and pruritus.,"['Q9H3N8', 'P35367', 'Q14994']","Pheniramine acts as an antagonist to allergic symptoms stemming from inappropriate histamine release to reduce edema, itching, and redness. The same antihistamine effect also produces sedation by acting in the central nervous system.1,9",CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=N1,"Pheniramine competes with histamine for the histamine H receptor, acting as an inverse agonist once bound.The reduction in H receptor activity is responsible for reduced itching as well as reduced vasodilation and capillary leakage leading to less redness and edema.This can be seen in the suppression of the histamine-induced wheal (swelling) and flare (vasodilation) response. Inverse agonism of the H receptor in the CNS is also responsible for the sedation produced by first-generation antihistamines like pheniramine.The binding of pheniramine to H receptors, and subsequent inverse agonism, may also contribute to reduced itching by antagonizing inflammation.TargetActionsOrganismAHistamine H receptorinverse agonistHumansAHistamine H receptorinverse agonistHumansUNuclear receptor subfamily group I member Not AvailableHumans",[],"['Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Antihistamines for Topical Use', 'Antipruritics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Dermatologicals', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Inverse Agonists', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents']" +DB05271,Rotigotine,Rotigotineis a non-selective dopamine agonist used for the treatment of Parkinson's Disease and Restless Leg Syndrome.,"['P35462', 'P21917', 'P14416', 'P21918', 'P21728', 'P08908', 'P18089']","Rotigotine is an agonist at all 5 dopamine receptor subtypes (D1-D5) but binds to the D3 receptor with the highest affinity. It is also an antagonist at α-2-adrenergic receptors and an agonist at the 5HT1A receptors. Rotigotine also inhibits dopamine uptake and prolactin secretion. There is no indication of a QT/QTc prolonging effect of Neupro in doses up to 24 mg/24 hours. The effects of Neupro at doses up to 24 mg/24 hours (supratherapeutic doses) on the QT/QTc interval was evaluated in a double-blind, randomized, placebo- and positive-controlled (moxifloxacin 400 mg IV, single dose) parallel-group trial with an overall treatment period of 52 days in male and female patients with advanced-stage Parkinson's disease. Assay sensitivity was confirmed by significant QTc prolongation by moxifloxacin.",CCCN(CCC1=CC=CS1)[C@H]1CCC2=C(O)C=CC=C2C1,"Rotigotine, a member of the dopamine agonist class of drugs, is delivered continuously through the skin (transdermal) using a silicone-based patch that is replaced every hours. A dopamine agonist works by activating dopamine receptors in the body, mimicking the effect of the neurotransmitter dopamine. The precise mechanism of action of rotigotine as a treatment for Restless Legs Syndrome is unknown but is thought to be related to its ability to stimulate dopamineTargetActionsOrganismADopamine D receptoragonistHumansADopamine D receptoragonistHumansADopamine D receptoragonistHumansUDopamine D receptoragonistHumansUDopamine D receptoragonistHumansU-hydroxytryptamine receptor AagonistHumansUAlpha-B adrenergic receptorantagonistHumans",[],"['Agents that produce hypertension', 'Anti-Parkinson Agents (Dopamine Agonist)', 'Anti-Parkinson Drugs', 'Antidepressive Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Agonists', 'Hypotensive Agents', 'Naphthalenes', 'Nervous System', 'Neurotransmitter Agents', 'Nonergot-derivative Dopamine Receptor Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Sulfur Compounds']" +DB09118,Stiripentol,Stiripentolis an antiepileptic agent used in combination with other anticonvulsants to treat seizures associated with Dravet syndrome.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P00338', 'P07195']","Stiripentol is an antiepileptic agent that works to reduce seizure frequency. It demonstrates anticonvulsant properties when administered alone and may potentiate GABAergic inhibition via several proposed mechanisms.4It provides a therapeutic advantage in improving the efficacy of other antiepileptic drugs by inhibiting cytochrome P450 enzymes that normally metabolize those drugs.8The anticonvulsant activity of stiripentol is age-dependent, with increased efficacy in younger patients.4",CC(C)(C)C(O)\C=C\C1=CC2=C(OCO2)C=C1,"The mechanism by which stiripentol exerts its anticonvulsant effect in humans has not been fully elucidated. Possible mechanisms of action include direct effects mediated through the gamma-aminobutyric acid GABAAreceptor and indirect effects involving inhibition of cytochrome P activity with a resulting increase in blood levels of clobazam and its active metabolite.Stiripentol is a positive allosteric modulator of GABAAreceptors in the brain that enhances the opening duration of the channel by binding to a site different than the benzodiazepine binding site.It binds to GABAAreceptors containing any of the α, β, γ, or δ-subunits but displays the most potent potency when bound to receptors containing α or δ subunits.Stiripentol also binds to GABAAreceptor-dependent chloride channels via a barbiturate-like mechanism.Stiripentol potentiates GABA transmission by enhancing the release of GABA,,reducing synaptosomal uptake of GABA,and inhibiting GABA transaminase-mediated breakdown of GABA.Stiripentol is an inhibitor of lactate dehydrogenase (LDH), which is involved in the energy metabolism of neurons and regulation of neuronal excitation. The drug binds to the site separate from the enzyme's lactate and pyruvate binding sites, thereby inhibiting both pyruvate-to-lactate conversion and lactate-to-pyruvate conversion.By inhibiting LDH, stiripentol may induce hyperpolarization, thereby reducing neuronal excitability.LDH inhibitors, including stiripentol, mimic a ketogenic diet, where the energy source in the brain is switched from glucose to mainly ketone bodies. The ketone bodies directly regulate neuronal excitation and seizures via ATP-sensitive potassium channels and vesicular glutamate transporters.Stiripentol is also suggested to exhibit neuroprotective properties, which may reduce injury caused by oxygen-glucose deprivation and glutamate excess.TargetActionsOrganismAGABA(A) Receptoragonistpositive allosteric modulatorHumansAL-lactate dehydrogenase A chaininhibitorHumansAL-lactate dehydrogenase B chaininhibitorHumans",[],"['Anticonvulsants', 'BCRP/ABCG2 Inhibitors', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dioxoles', 'Drugs causing inadvertant photosensitivity', 'Drugs that are Mainly Renally Excreted', 'Miscellaneous Anticonvulsants', 'Nervous System', 'P-glycoprotein inhibitors', 'Photosensitizing Agents']" +DB04872,Osanetant,"Developed by Sanofi-Aventis (formerly Sanofi-Synthelabo), osanetant (SR-142801) is an NK3 receptor antagonist which was under development for the treatment of schizophrenia and other Central Nervous System (CNS) disorders. In a review of its R&D portfolio, the company announced in August 2005 that it would cease any further development of osanetant. This follows an earlier decision to discontinue development of eplivanserin for schizophrenia.",['P29371'],Osanetant is a neurokinin-3 (NK3) receptor antagonist. Preliminary clinical trials have demonstrated that osanetant is superior to placebo on global assessment of efficacy and measures of positive symptoms in schizophrenia.,CN(C(C)=O)C1(CCN(CCC[C@@]2(CCCN(C2)C(=O)C2=CC=CC=C2)C2=CC(Cl)=C(Cl)C=C2)CC1)C1=CC=CC=C1,"The mechanism of action of osanetant is uncertain at this point. Various preclinical data indicate that activation of NK receptors enhances the release of biogenic amines, including dopamine and serotonin. NK receptor antagonists could block NK-receptor-mediated activation of these systems.TargetActionsOrganismUNeuromedin-K receptorNot AvailableHumans",[],"['Antipsychotic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Neurotoxic agents', 'Psychotropic Drugs', 'Tranquilizing Agents']" +DB09097,Quinagolide,Quinagolideis a dopamine D2 receptor agonist used for the treatment of hyperprolactinemia.,"['P14416', 'P21728', 'P21918']",Quinagolide achieves long-lasting reduction in prolactin levels in a dose-proportional effect via selectively targeting D2 receptors as an agonist. It potently suppresses both basal and stimulated serum prolactin levels by exerting a strong inhibitory effect on the secretion of the anterior pituitary hormone prolactin.,[H][C@]12C[C@@H](CN(CCC)[C@]1([H])CC1=CC=CC(O)=C1C2)NS(=O)(=O)N(CC)CC,"Prolactin secretion from the lactotroph cells present in the anterior pituiatry gland is under tonic inhibitory control mediated by dopaminergic signalling via D receptors. Quinagolide selectively binds to D receptors expressed on the surface of lactotroph cells with high affinity which results in reduced adenylyl cyclase activity, reduced intracellular cyclic adenosine monophosphate and inhibited prolactin secretion. It also binds to D receptors but with low affinity and little clinical relevance.TargetActionsOrganismUDopamine D receptoragonistHumansUD() dopamine receptoragonistHumans",[],"['Dopamine Agents', 'Dopamine Agonists', 'Dopamine D2 Receptor Agonists', 'Genito Urinary System and Sex Hormones', 'Heterocyclic Compounds, Fused-Ring', 'Miscellaneous Therapeutic Agents', 'Neurotransmitter Agents', 'Prolactine Inhibitors', 'Quinolines']" +DB01071,Mequitazine,"Mequitazine is a histamine H1 antagonist (antihistamine). It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",['P35367'],"In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Mequitazine is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",C(C1CN2CCC1CC2)N1C2=CC=CC=C2SC2=CC=CC=C12,"Mequitazine binds to the histamine H receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Anti-Allergic Agents', 'Antihistamines for Systemic Use', 'Bronchodilator Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Neurotransmitter Agents', 'Phenothiazine Derivatives', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Sulfur Compounds']" +DB00891,Sulfapyridine,"Sulfapyridineis a sulfonamide antibiotic used to treat dermatitis herpetiformis, benign mucous membrane pemphigoid and pyoderma gangrenosum.",['Q49184'],"Sulfapyridine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors ofp-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.",NC1=CC=C(C=C1)S(=O)(=O)NC1=CC=CC=N1,"Sulfapyridine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid by means of processing the substrate para-aminobenzoic acid (PABA). Dihydropteroate synthetase activity is vital in the synthesis of folate, and folate is required for cells to make nucleic acids, such as DNA or RNA. So if DNA molecules cannot be built, the cell cannot divide.TargetActionsOrganismUDihydropteroate synthase type-inhibitorMycobacterium fortuitum",[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Benzene Derivatives', 'Benzenesulfonamides', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Methemoglobinemia Associated Agents', 'Short-Acting Antibacterial Sulfonamides', 'Sulfanilamides', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds']" +DB09214,Dexketoprofen,Dexketoprofenis an NSAID that is the R(-)-enantiomer of racemic ketoprofen with analgesic and anti-inflammatory properties used for the treatment of mild to moderate pain.,"['P23219', 'P35354']","This drug is an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties3.",[H][C@@](C)(C(O)=O)C1=CC(=CC=C1)C(=O)C1=CC=CC=C1,It is a non-steroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis via inhibition of cyclooxygenase pathway (both COX- and COX-) activity.TargetActionsOrganismUProstaglandin G/H synthase antagonistHumansUProstaglandin G/H synthase antagonistHumans,[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Alcohols', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antirheumatic Agents', 'Central Nervous System Agents', 'Drugs that are Mainly Renally Excreted', 'Glycols', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Phenylpropionates', 'Propionates', 'Propylene Glycols', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain']" +DB00606,Cyclothiazide,"As a diuretic, cyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like cyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of cyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.","['P54710', 'P00915', 'Q8N1Q1', 'Q9ULX7', 'P00918', 'P07451', 'P22748', 'P35218', 'Q9Y2D0', 'P23280', 'P43166', 'Q16790', 'P00915', 'P00918', 'Q6FHJ7']","Like other thiazides, cyclothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl-reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Cyclothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Cyclothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.",NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C1CC2CC1C=C2,"Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLCA) in the distal convoluted tubule, which is responsible for % of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLCA) in the distal convoluted tubule, which is responsible for % of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.TargetActionsOrganismASodium/potassium-transporting ATPase subunit gammainhibitorHumansACarbonic anhydraseinhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUSecreted frizzled-related protein inhibitorHumans",[],"['Antihypertensive Agents', 'Cardiovascular Agents', 'Diuretics', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Hyperglycemia-Associated Agents', 'Natriuretic Agents', 'OAT1/SLC22A6 inhibitors', 'Receptors, AMPA', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazides']" +DB08807,Bopindolol,Bopindolol (INN) is an ester prodrug for the beta blockerpindolol.,"['P08588', 'P07550', 'P08908', 'P28222', 'P13945']","Bopindolol is a prodrug of pindolol. Pindolol is a non-selective beta-adrenergic antagonist (beta-blocker) which possesses intrinsic sympathomimetic activity (ISA) in therapeutic dosage ranges but does not possess quinidine-like membrane stabilizing activity. Pindolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Pindolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Pindolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, pindolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.",CC1=CC2=C(N1)C=CC=C2OCC(CNC(C)(C)C)OC(=O)C1=CC=CC=C1,"Bopindolol (as pindolol) non-selectively blocks beta- adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. By binding beta- receptors in the juxtaglomerular apparatus, Pindolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.TargetActionsOrganismABeta- adrenergic receptorantagonistpartial agonistHumansABeta- adrenergic receptorantagonistpartial agonistHumansU-hydroxytryptamine receptor ANot AvailableHumansU-hydroxytryptamine receptor BNot AvailableHumansUBeta- adrenergic receptorNot AvailableHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Beta Blocking Agents, Non-Selective', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Neurotransmitter Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols']" +DB01359,Penbutolol,"Penbutololis a beta-adrenergic antagonist used for the management of mild to moderate arterial hypertension, alone or in combination with other antihypertensive agents.","['P08588', 'P07550', 'P08908', 'P28222']","Penbutolol is a ß-1, ß-2 (nonselective) adrenergic receptor antagonist. Experimental studies showed a dose-dependent increase in heart rate in reserpinized (norepinephrine-depleted) rats given penbutolol intravenously at doses of 0.25 to 1.0 mg/kg, suggesting that penbutolol has some intrinsic sympathomimetic activity. In human studies, however, heart rate decreases have been similar to those seen with propranolol.",CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1,"Penbutolol acts on the β adrenergic receptors in both the heart and the kidney. When β receptors are activated by catecholamines, they stimulate a coupled G protein that leads to the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases the heart rate. Penbutolol blocks the catecholamine activation of β adrenergic receptors and decreases heart rate, which lowers blood pressure.TargetActionsOrganismABeta- adrenergic receptorantagonistpartial agonistHumansABeta- adrenergic receptorantagonistpartial agonistHumansA-hydroxytryptamine receptor AantagonistHumansU-hydroxytryptamine receptor BantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antidepressive Agents', 'Antihypertensive Agents', 'Beta Blocking Agents, Non-Selective', 'Bradycardia-Causing Agents', 'Cardiovascular Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Negative Inotrope', 'Neurotransmitter Agents', 'Phenoxypropanolamines', 'Propanolamines', 'Propanols', 'Serotonin 5-HT1 Receptor Antagonists', 'Serotonin 5-HT1A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB00651,Dyphylline,"Dyphyllineis a theophylline derivative used to treat asthma, bronchospasm, and COPD.","['Q07343', 'P27815', 'Q08493', 'Q08499', 'P30542', 'P29274']","Dyphylline, a xanthine derivative, is a bronchodilator used for relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Dyphylline is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree.",CN1C2=C(N(CC(O)CO)C=N2)C(=O)N(C)C1=O,"The bronchodilatory action of dyphylline, as with other xanthines, is thought to be mediated through competitive inhibition of phosphodiesterase with a resulting increase in cyclic AMP producing relaxation of bronchial smooth muscle as well as antagonism of adenosine receptors.TargetActionsOrganismAcAMP-specific ','-cyclic phosphodiesterase BinhibitorHumansAcAMP-specific ','-cyclic phosphodiesterase AinhibitorHumansAcAMP-specific ','-cyclic phosphodiesterase CinhibitorHumansAcAMP-specific ','-cyclic phosphodiesterase DinhibitorHumansAAdenosine receptor AantagonistHumansAAdenosine receptor AaantagonistHumans",[],"['Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiovascular Agents', 'Drugs for Obstructive Airway Diseases', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Peripheral Nervous System Agents', 'Phosphodiesterase Inhibitors', 'Purines', 'Purinones', 'Respiratory System Agents', 'Vasodilating Agents', 'Xanthine derivatives', 'Xanthines and Adrenergics']" +DB09229,Aranidipine,"Aranidipine is a novel dihydropyridine derivative that gives rise to two active metabolites (M-1α and M-1β) that exhibit hypotensive activity. It is a calcium antagonist with the formula methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate.1It was developed by Maruko Seiyaku, introduced by Taiho and launched in Japan in 1997.5","['Q13936', 'Q01668', 'O60840', 'Q13698', 'P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825', 'O95180']","Pre-clinical studies with aranidipine and its two metabolites have shown production of increases in femoral blood flow. It has been shown to present potent and long-lasting vasodilating actions. Aranidipine and its metabolites are shown to inhibit calcium-induced contraction in isolated rabbit arteries.1Studies have shown that aranidipine is more potent to reduce blood pressure than other dihydropyridines.2Aranidipine produce changes in renal blood flow, this effect may be explained by its effect on alpha-2-adrenoreceptor-mediated vasoconstriction.4",COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OCC(C)=O,"The high potential of aranidipine is thought to be related to the additional calcium antagonistic activity of its metabolite. The mechanism is thought to be related to the capacity of aranidipine and its metabolites to vasodilate afferent and efferent arterioles. this action is performed through the inhibition of voltage-dependent calcium channels.The typical mechanism of action of aranidipine, as all dihydropyridines, is based on the inhibition of L-type calcium channels, decreasing calcium concentration and inducing smooth muscle relaxation.It is a selective alpha-adrenoreceptor antagonist which inhibits vasoconstrictive responses.TargetActionsOrganismAVoltage-dependent L-type calcium channel subunit alpha-CantagonistHumansAVoltage-dependent L-type calcium channel subunit alpha-DantagonistHumansAVoltage-dependent L-type calcium channel subunit alpha-FantagonistHumansAVoltage-dependent L-type calcium channel subunit alpha-SantagonistHumansUAlpha adrenergic receptoragonistHumansUVoltage-dependent T-type calcium channel subunit alpha-HinhibitorHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Vasodilating Agents']" +DB00212,Remikiren,"Remikiren is an orally active, high specificity renin inhibitor.",['P00797'],"Remikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.",CC(C)(C)S(=O)(=O)C[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)C1CC1,Several in vivo experiments have shown that remikiren is specific for renin and does not decrease arterial pressure by an unrelated mechanism.TargetActionsOrganismARenininhibitorHumans,[],"['Agents Acting on the Renin-Angiotensin System', 'Antihypertensive Agents', 'Cardiovascular Agents', 'Enzyme Inhibitors', 'Protease Inhibitors', 'Renin Inhibitors']" +DB01295,Bevantolol,"Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension. Mechanism of Action Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta-1 receptors.","['P08588', 'P07550', 'P35348']",Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension.,COC1=C(OC)C=C(CCNCC(O)COC2=CC=CC(C)=C2)C=C1,"Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta- receptors. By binding and antagonizing beta- receptors Bevantolol inhibits the normal normal epinephrine-mediated sympathetic actions such as increased heart rate. This has the effect of decreasing preload and blood pressure.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansUBeta- adrenergic receptorantagonistHumansUAlpha-A adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Adrenergic beta-1 Receptor Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Antihypertensive Agents', 'Beta Blocking Agents and Thiazides', 'Beta Blocking Agents, Selective', 'Beta Blocking Agents, Selective, and Thiazides', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Neurotransmitter Agents', 'Propanols']" +DB00226,Guanadrel,Guanadrel is an antihypertensive agent and postganglionic adrenergic blocking agent.,['P23975'],"High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanadrel works by controlling nerve impulses along certain nerve pathways. As a result, it relaxes the blood vessels so that blood passes through them more easily. This helps to lower blood pressure.",NC(N)=NCC1COC2(CCCCC2)O1,"Guanadrel is an adrenergic neuron inhibitor that slowly displaces norepinephrine from its storage in nerve endings. It blocks the release of norepinephrine in response to the sympathetic nerve stimulation, leading to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position.TargetActionsOrganismASodium-dependent noradrenaline transporterpartial agonistHumans",[],"['Adrenergic Antagonists', 'Amidines', 'Antihypertensive Agents', 'Cardiovascular Agents']" +DB01134,Desoxycorticosterone pivalate,"Desoxycorticosterone pivalate is a mineralocorticoid hormone and an analog of desoxycorticosterone. It is white, odorless, and stable in air. It is practically insoluble in water, sparingly soluble in acetone, slightly soluble in methanol, ether and vegetable oils. Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.",['P08235'],"Used to treat adrenocortical insufficiency, desoxycorticosterone pivalate is a mineralocorticoid hormone and an analogue of desoxycorticosterone. It primarily acts on the metabolism of sodium, potassium and water. When the drug is given, there is decreased excretion of sodium accompanied by increased excretion of potassium; the concentration of sodium in the blood is thereby increased whereas that of potassium is decreased. There is a concomitant increase in the volume of blood and extracellular fluids, with a fall in hematocrit. It increases the rate of renal tubular absorption of sodium.",[H][C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)C(=O)COC(=O)C(C)(C)C,"Desoxycorticosterone Pivalate binds to the mineralocorticoid receptor. Mineralocorticoids are a family of steroids, secreted by the adrenal cortex, necessary for the regulation of a number of metabolic processes including electrolyte regulation. Desoxycorticosterone pivalate exerts its effect through its interaction with the mineralocorticoid receptor (MR), whereby it reacts with the receptor proteins to form a steroid-receptor complex. This complex moves into the nucleus, where it binds to chromatin which results in genetic transcription of cellular DNA to messenger RNA. The steroid hormones appear to induce transcription and synthesis of specific proteins, which produce the physiological effects seen after administration.TargetActionsOrganismAMineralocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Corticosteroids', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hydroxycorticosteroids', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Steroids']" +DB09236,Lacidipine,Lacidipineis a lipophilic dihydropyridine calcium channel blocker with a slow onset of action used to treat hypertension.,"['Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555']","acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure6.Following the oral administration of 4 mg lacidipine to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers)6.",CCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C)C(=O)OCC,"By blocking the voltage-dependent L-type calcium channels, it prevents the transmembrane calcium influx. Normally, calcium ions serve as intracellular messengers or activators in exictable cells including vascular smooth muscles. The influx of calcium ultimately causes the excitation and depolarization of the tissues. Lacidipine inhibits the contractile function in the vascular smooth muscle and reduce blood pressure. Due to its high membrane partition coefficient, some studies suggest that lacidipine may reach the receptor via a two-step process; it first binds and accumulates in the membrane lipid bilayer and then diffuses within the membrane to the calcium channel receptor. It is proposed that lacidipine preferentially blocks the inactivated state of the calcium channel.Through its antioxidant properties shared amongst other dihydropyridine calcium channel blockers, lacidipine demonstrates an additional clinical benefit. Its antiatherosclerotic effects are mediated by suppressing the formation of reactive oxygen species (ROS) and subsequent inflammatory actions by chemokines, cytokines and adhesion molecules, thus reducing atherosclerotic lesion formation. Lacidipine may also suppress cell proliferation and migration in smooth muscle cells and suppress the expression of matrix metalloproteinases, which affects the stability of atheromatous plaques.TargetActionsOrganismAVoltage-dependent L-type calcium channelantagonistHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Mutagens', 'Potential QTc-Prolonging Agents', 'Pyridines', 'QTc Prolonging Agents', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00782,Propantheline,"Propanthelineis an antimuscarinic agent used to treat urinary incontinence, hyperhidrosis, as well as cramps and spasms of the stomach, intestines, and bladder.",['P11229'],"Propantheline is an anticholinergic drug, a medication that reduces the effect of acetylcholine, a chemical released from nerves that stimulates muscles, by blocking the receptors for acetylcholine on smooth muscle (a type of muscle). It also has a direct relaxing effect on smooth muscle. Propantheline is used to treat or prevent spasm in the muscles of the gastrointestinal tract in the irritable bowel syndrome. In addition, Propantheline inhibits gastrointestinal propulsive motility and decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretions.",CC(C)[N+](C)(CCOC(=O)C1C2=CC=CC=C2OC2=CC=CC=C12)C(C)C,Action is achieved via a dual mechanism: () a specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor sites and () a direct effect upon smooth muscle (musculotropic).TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumans,[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Amines', 'Anti-Ulcer Agents', 'Anticholinergic Agents', 'Cholinergic Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Onium Compounds', 'Quaternary Ammonium Compounds', 'Synthetic Anticholinergics, Quaternary Ammonium Compounds', 'Xanthenes']" +DB01399,Salsalate,"Salsalateis a nonsteroidal anti-inflammatory agent used in the symptomatic relief of rheumatoid arthritis, osteoarthritis and related rheumatic disorders.","['P35354', 'P23219']","Salsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo.",OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O,"The mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase- (COX-) and COX-, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salsalate) is a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, salsalate does not inhibit platelet aggregation.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Acids, Carbocyclic', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzoates', 'Hydroxy Acids', 'Hydroxybenzoates', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Phenols', 'Salicylic Acid and Derivatives', 'Sensory System Agents']" +DB00980,Ramelteon,Ramelteonis a melatonin receptor agonist used to treat insomnia.,"['P49286', 'P48039']","Ramelteon is the first selective melatonin agonist. It works by mimicking melatonin (MT), a naturally occuring hormone that is produced during the sleep period and thought to be responsible for the regulation of circadian rhythm underlying the normal sleep-wake cycle. Ramelteon has a high affinity for the MT1and MT2receptors. The MT1and MT2receptors are located in the brain's suprachiasmatic nuclei (SCN),which is known as the body's ""master clock"" because it regulates the 24-hour sleep-wake cycle. Ramelteon has an active metabolite that is less potent but circulates in higher concentrations than the parent compound. The metabolite also has weak affinity for the 5HT2b receptor.",CCC(=O)NCC[C@@H]1CCC2=C1C1=C(OCC1)C=C2,"Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MTand MTreceptors, and lower selectivity for the MTreceptor. Melatonin production is concurrent with nocturnal sleep, meaning that an increase in melatonin levels is related to the onset of self-reported sleepiness and an increase in sleep propensity. MTreceptors are believed to be responsible for regulation of sleepiness and facilitation of sleep onset, and MTreceptors are believed to mediate phase-shifting effects of melatonin on the circadian rhythm. While MTand MTreceptors are associated with the sleep-wake cycle, MThas a completely different profile, and therefore is not likely to be involved in the sleep-wake cycle. Remelteon has no appreciable affinity for the gamma-aminobutyric acid (GABA) receptor complex or receptors that bind neuropeptides, cytokines, serotonin, dopamine, norepinephrine, acetylcholine, or opiates.TargetActionsOrganismAMelatonin receptor type BmultitargetHumansAMelatonin receptor type AmultitargetHumans",[],"['Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypnotics and Sedatives', 'Melatonin Receptor Agonists', 'Nervous System', 'Psycholeptics']" +DB04920,Clevidipine,Clevidipineis a dihydropyridine L-type calcium channel blocker used to lower blood pressure when oral antihypertensive therapy is not feasible or not desirable.,"['O60840', 'Q13698', 'Q01668', 'Q13936']","Clevidipine belongs to a well-known class of drugs called dihydropyridine calcium channel antagonists. Clevidpine is the first third generation intravenous dihydropyridine calcium channel blocker. In vitro studies demonstrated that clevidipine acts by selectively relaxing the smooth muscle cells that line small arteries, resulting in arterial dilation, widening of the artery opening, and without reducing central venous pressure or reducing cardiac output.",CCCC(=O)OCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC(Cl)=C1Cl)C(=O)OC,"Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, clevidipine inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.TargetActionsOrganismUVoltage-dependent L-type calcium channel subunit alpha-FNot AvailableHumansUVoltage-dependent L-type calcium channel subunit alpha-SNot AvailableHumansUVoltage-dependent L-type calcium channel subunit alpha-DNot AvailableHumansUVoltage-dependent L-type calcium channel subunit alpha-CNot AvailableHumans",[],"['Agents causing hyperkalemia', 'Antiarrhythmic agents', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Calcium Channel Blockers (Dihydropyridine)', 'Calcium-Regulating Hormones and Agents', 'Cardiovascular Agents', 'Cholinesterase substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Dihydropyridine Derivatives', 'Dihydropyridines', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Membrane Transport Modulators', 'Selective Calcium Channel Blockers With Mainly Vascular Effects', 'Vasodilating Agents']" +DB00876,Eprosartan,"Eprosartanis an ARB used to treat hypertension, diabetic nephropathy, and congestive heart failure.",['P30556'],"Angiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme [kininase II]. It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT1receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.",CCCCC1=NC=C(\C=C(/CC2=CC=CS2)C(O)=O)N1CC1=CC=C(C=C1)C(O)=O,"Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATreceptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an ATreceptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Eprosartan does not exhibit any partial agonist activity at the ATreceptor. Its affinity for the ATreceptor is , times greater than for the ATreceptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the ATreceptor. Eprosartan has also been shown to bind to ATreceptors both presynaptically and synaptically. Its action on presynaptic ATreceptors results in the inhibition of sympathetically stimulated noradrenaline release. Unlike ACE inhibitors, eprosartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).TargetActionsOrganismAType- angiotensin II receptorantagonistHumans",[],"['Acids, Acyclic', 'Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents Causing Muscle Toxicity', 'Angiotensin 2 Receptor Blocker', 'Angiotensin II receptor antagonists', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin II Type 1 Receptor Blockers', 'Angiotensin Receptor Antagonists', 'Antihypertensive Agents', 'Antihypertensive Agents Indicated for Hypertension', 'Cardiovascular Agents', 'Hypotensive Agents', 'Sulfur Compounds']" +DB09279,Fimasartan,Fimasartanis an angiotensin II receptor antagonist (ARB) used to treat hypertension and heart failure.,['P30556'],Fimasartan is a selective angiotensin receptor 1 (AR1) inhibitor1. It acts to lower blood pressure by inhibiting vasoconstriction,CCCCC1=NC(C)=C(CC(=S)N(C)C)C(=O)N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1,"Angiotensin II activates AR leading to vasoconstriction and increased noradrenaline release which further increases vasoconstriction via action at α-adrenergic receptors,. It also stimulates secretion of aldosterone which acts to increase sodium and water reabsorption in the renal tubules. Fimasartan bind to and antagonizes AR preventing vasoconstriction and reducing aldosterone secretion to increase natriuresis leading to a reduction in blood volume. Together these effects produce an anti-hypertensive effect.TargetActionsOrganismAType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing hyperkalemia', 'Angiotensin II receptor blockers (ARBs) and calcium channel blockers', 'Angiotensin II receptor blockers (ARBs) and diuretics', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin Receptor Antagonists', 'BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'Hypotensive Agents', 'Lipid Modifying Agents', 'OATP1B1/SLCO1B1 Substrates']" +DB06403,Ambrisentan,Ambrisentanis a selective type A endothelin receptor antagonist used to treat primary pulmonary arterial hypertension and pulmonary arterial hypertension based on diagnostic classifications.,"['P25101', 'P24530']","Ambrisentan 10 mg daily had no significant effect on the QTc interval, whereas a 40 mg daily dose of ambrisentan increased mean QTc at tmax by 5 ms with an upper 95% confidence limit of 9 ms. Significant QTc prolongation is not expected in patients taking ambrisentan without concomitant metabolic inhibitors. +Plasma concentrations of B-type natriuretic peptide (BNP) in patients who received ambrisentan for 12 weeks were significantly decreased. Two Phase III placebo-controlled studies demonstrated a decrease in BNP plasma concentrations by 29% in the 2.5 mg group, 30% in the 5 mg group, and 45% in the 10 mg group (p < 0.001 for each dose group) and an increase by 11% in the placebo group.",COC([C@H](OC1=NC(C)=CC(C)=N1)C(O)=O)(C1=CC=CC=C1)C1=CC=CC=C1,"Endothelin- (ET-) is an endogenous peptide that acts on the endothelin type A (ETA) and endothelin type B (ETB) receptors in vascular smooth muscle and endothelium. ETA-mediated actions include vasoconstriction and cell proliferation, whereas ETB predominantly mediates vasodilation, anti-proliferation, and ET- clearance. In patients with pulmonary arterial hypertension, ET- levels are increased and correlate with increased right arterial pressure and severity of disease. +Ambrisentan is one of several newly developed vasodilator drugs that selectively target the endothelin type A (ETA) receptor, inhibiting its action and preventing vasoconstriction. Selective inhibition of the ETA receptor prevents phospholipase C-mediated vasoconstriction and protein kinase C-mediated cell proliferation. Endothelin type B (ETB) receptor function is not significantly inhibited, and nitric oxide and prostacyclin production, cyclic GMP- and cyclic AMP-mediated vasodilation, and endothelin- (ET-) clearance is preserved.TargetActionsOrganismAEndothelin- receptorantagonistHumansNEndothelin B receptorantagonistHumans",[],"['Acids, Carbocyclic', 'Antihypertensive Agents', 'Antihypertensives for Pulmonary Arterial Hypertension', 'Cardiovascular Agents', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Endothelin Receptor Antagonists', 'Hypertension, Pulmonary', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 substrates', 'P-glycoprotein substrates', 'UGT1A3 substrates', 'UGT1A9 Substrates', 'UGT2B7 substrates', 'Vasodilating Agents']" +DB09418,Potassium perchlorate,"Potassium perchlorate is an inorganic salt with the chemical formula KClO4. It is a strong oxidizer with the lowest solubility of the alkali metal perchlorates. Potassium is most commonly used in flares and automobile airbags1. The use of potassium perchlorate as a component in sealing gaskets for food containers has been revoked by the FDA following the use being abandoned by the industry7. Potassium perchlorate acts as a competitive inhibitor of iodine uptake by the thyroid gland and attenuates the production of the thyroid hormone. Thus the use of potassium perchlorate has been extensive for hyperthyroidism during the last 50 years, particularly in the late 1950s and early 1960s1. The therapeutic use of potassium perchlorate in thyroid disorders has been ceased due to a high risk for developing aplastic anemia and nephrotic syndrome6.",['Q92911'],"Potassium perchlorate inhibits thyroid iodide transport. The clinical use of potassium perchlorate in hyperthyroidism, such as Graves' disease and amiodarone-induced hypothyroidism, have been investigated in various studies. Thyroid dysfunction occurs in about 15-20% of the patients receiving long-term amiodarone therapy2. In patients with amiodarone-induced hypothyroidism, short-term administration of potassium perchlorate resulted in restoration of euthyroidism in most patients4. Euthyroidism promoted by potassium perchlorate does not persist unless amiodarone treatment is withdrawn2.",[K+].[O-][Cl](=O)(=O)=O,"Thyroxine (T) and tri-iodothyronine (T) are major thyroid hormones, or iodothyronines, that are synthesized and released from the thyroid. Iodine plays an essential role in the synthesis of these hormones. Via the sodium-iodide symporter (NIS), which is a protein located on the basolateral membrane of the thyroid follicular cell, iodine is transported from the blood into the thyroid gland where it is oxidized to. Perchlorate (ClO−) is the dissociated anion of potassium perchlorate that exerts an inhibitory effect on iodide uptake by the thyroid gland in the cellular level. Due to its similarity in ionic size and charge to iodide, perchlorate inhibits the sodium-iodide symporter (NIS) without being translocated into the thyroid follicular cell. The inhibition constant, Ki, is estimated as . µmol to µmol. At therapeutic dosage levels this competitive inhibition decreases the entrance of iodide into the thyroid, resulting in less available iodide for hormone synthesis and, therefore, a decrease in T and T synthesis. When ambient iodine intake is low or iodide uptake is sufficiently inhibited, perchlorate is capable in inducing goiter and hypothyroidism from inhibited iodide uptake. At high doses of potassium perchlorate, reduced T and T levels may be accompanied by increased TSH levels via a negative feedback loop, affecting the thyroid, pituitary and hypothalamus.TargetActionsOrganismASodium/iodide cotransporterinhibitorHumans",[],"['Acids', 'Acids, Noncarboxylic', 'Antithyroid agents', 'Chlorine Compounds', 'Drugs that are Mainly Renally Excreted', 'Perchlorates', 'Potassium Salt', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroid Products']" +DB09020,Bisacodyl,Bisacodylis a stimulant laxative used for the temporary relief of occasional constipation and cleansing of the colon as a preparation for colonoscopy in adults.,"['Q92482', 'P05023', 'P50993', 'P13637', 'Q13733', 'P05026', 'P14415', 'P54709', 'P54710']","Patients should be counselled regarding abdominal pain, nausea, vomiting, or a change in bowel function that lasts longer than 2 weeks.9It has a wide therapeutic index, as patients can take 5-15 mg orally.9Patients taking bisacodyl should be counselled before taking the medication if they are already experiencing abdominal pain, nausea, vomiting, or a change in bowel function lasting longer than 2 weeks.9Patients should also be counselled to stop taking the medication if they experience rectal bleeding or no bowel movement in 12 hours.9",CC(=O)OC1=CC=C(C=C1)C(C1=CC=C(OC(C)=O)C=C1)C1=CC=CC=N1,"Bisacodyl is deacetylated to the active bis-(p-hydroxyphenyl)-pyridyl--methane (BHPM) by an intestinal deacetylase.,,BHPM can stimulate parasympathetic nerves in the colon directly to increase motility and secretions.Bisacodyl stimulates adenylate cyclase, increasing cyclic AMP, leading to active transport of chloride and bicarbonate out of cells.Sodium ions, potassium ions, and water passively leave the cell; while sodium and chloride ions are unable to be reabsorbed.Water is also be transported from the luminal side of cells into the vasculature by aquaporin .Bisacodyl decreases expression of aquaporin , preventing water from moving into the vasculature, which may contribute to increased water in the colon.Bisacodyl directly stimulates parasympathetic nerves in the colon, stimulating contraction of longitudinal smooth muscle but not circular smooth muscle.,TargetActionsOrganismUAquaporin-negative modulatorHumansUSodium/Potassium Transporting ATPaseinhibitorHumans",['Bowel preparation therapy'],"['Alimentary Tract and Metabolism', 'Benzene Derivatives', 'Contact Laxatives', 'Cresols', 'Drugs for Constipation', 'Enemas', 'Gastrointestinal Agents', 'Increased Large Intestinal Motility', 'Laxatives', 'Phenols', 'Stimulation Large Intestine Fluid/Electrolyte Secretion']" +DB00872,Conivaptan,Conivaptanis an antidiuretic hormone inhibitor used to raise serum sodium levels.,"['P37288', 'P30518']","Conivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V1Aand V2receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V2receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water. Vasopressin also causes vasoconstriction through its actions on vascular1Areceptors. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V2antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. Conivaptan's antagonist activity on V1Areceptors may also cause splanchnic vasodilation, resulting in possible hypotension or variceal bleeding in patients with cirrhosis. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.",CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1,"Conivaptan is a dual AVP antagonist with nanomolar affinity for human arginine vasopressin VAand Vreceptorsin vitro. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.TargetActionsOrganismAVasopressin Va receptorantagonistHumansAVasopressin V receptorantagonistHumans",[],"['Antidiuretic Hormone Receptor Antagonists', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Diuretics', 'Heterocyclic Compounds, Fused-Ring', 'Hypotensive Agents', 'Narrow Therapeutic Index Drugs', 'Natriuretic Agents', 'P-glycoprotein inhibitors']" +DB09059,Atosiban,Atosibanis an inhibitor of oxytocin and vasopressin used to delay imminent preterm birth in pregnant adult women displaying specific clinical observations.,"['P30559', 'P37288', 'P47901', 'P30518']","Atosiban reduces the frequency of uterine contractions to delay pre-term birth in adult females and induces uterine quiescence5,1.",[H][C@]1(NC(=O)[C@@]([H])(NC(=O)[C@@H](CC2=CC=C(OCC)C=C2)NC(=O)CCSSC[C@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)[C@@H](C)CC)[C@@H](C)O,"Atosiban is a synthetic peptide oxytocin antagonist,. It resembles oxytocin with has modifications at the , , , and positions. The N-terminus of the cysteine residue is deaminated to form -mercaptopropanic acid at position , at position L-tyrosine is modified to D-tyrosine with an ethoxy group replacing the phenol , threonine replaces glutamine at postion , and ornithine replaces leucine at position .It binds to membrane bound oxytocin receptors on the myometrium and prevents oxytocin-stimulated increases in inositol triphosphate production. This ultimately prevents release of stored calcium from the sarcoplasmic reticulum and subsequent opening of voltage gated calcium channels. This shutdown of cytosolic calcium increase prevents contractions of the uterine muscle, reducing the frequency of contractions and inducing uterine quiescence.Atosiban has more recently been found to act as a biased ligand at oxytocin receptors,. It acts as an antagonist of Gq coupling, explaining the inhibition of the inositol triphosphate pathway thought to be responsible for the effect on uterine contraction, but acts as an agonist of Gi coupling. This agonism produces a pro-inflammatory effect in the human amnion, activating pro-inflammatory signal tranducer NF-κB. It is thought that this reduces atosiban's effectiveness compared to agents which do not produce inflammation as inflammatory mediators are known to play a role in the induction of labour.TargetActionsOrganismAOxytocin receptorantagonistHumansUVasopressin Va receptorantagonistHumansUVasopressin Vb receptorantagonistHumansUVasopressin V receptorantagonistHumans",[],"['Amino Acids, Peptides, and Proteins', 'Genito Urinary System and Sex Hormones', 'Hormone Antagonists', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Peptide Hormones', 'Peptides', 'Pituitary Hormones', 'Pituitary Hormones, Posterior', 'Reproductive Control Agents', 'Tocolytic Agents']" +DB01612,Amyl Nitrite,Amyl Nitriteis a fast acting vasodilator used for rapid relief of angina pectoris.,['P16066'],"Amyl nitrite, in common with other alkyl nitrites, is a potent vasodilator. It expands blood vessels, resulting in lowering of the blood pressure. Alkyl nitrite functions as a source of nitric oxide, which signals for relaxation of the involuntary muscles. Adverse effects are related to this pharmacological activity and include hypotension, headache, flushing of the face, tachycardia, dizziness, and relaxation of involuntary muscles, especially the blood vessel walls and the anal sphincter.",CCCCCON=O,"Amyl nitrite's antianginal action is thought to be the result of a reduction in systemic and pulmonary arterial pressure (afterload) and decreased cardiac output because of peripheral vasodilation, rather than coronary artery dilation. Amyl nitrite is a source of nitric oxide, which accounts for the mechanism described above. As an antidote (to cyanide poisoning), amyl nitrite promotes formation of methemoglobin, which combines with cyanide to form nontoxic cyanmethemoglobin.TargetActionsOrganismAAtrial natriuretic peptide receptor agonistHumans",[],"['Antianginal Agents', 'Antidotes', 'Cardiovascular Agents', 'Hypotensive Agents', 'Methemoglobinemia Associated Agents', 'Nitrites', 'Organic Nitrates', 'Vasodilating Agents']" +DB00418,Secobarbital,Secobarbitalis a barbiturate used for the short-term treatment of insomnia.,"['P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P14867', 'P43681', 'P36544', 'P42262', 'Q13002', 'Q05586', 'Q12879', 'Q13224', 'Q14957', 'O15399', 'Q8TCU5', 'O60391']","Secobarbital, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.",CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O,"Secobarbital binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumansUNMDA receptorantagonistHumans",['Anesthetic premedication therapy'],"['Adjuvants', 'Adjuvants, Anesthesia', 'Anticholinergic Agents', 'Anticonvulsants', 'Barbiturates', 'Barbiturates, Plain', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strong)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Modulators', 'Hypnotics and Sedatives', 'Nervous System', 'Neurotransmitter Agents', 'Nicotinic Antagonists', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones']" +DB09205,Moxisylyte,"Moxisylyte, denominated as thymoxamine in the UK, is a specific and orally active α1-adrenergic antagonist.10According to the WHO, moxisylyte is approved since 19879and in the same year, it acquired the denomination of orphan product by the FDA.11This drug was developed by the Japanese company Fujirebio and also by the American company Iolab in the late 80s.","['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']",Administration of moxisylyte has shown to improve peripheral flow in occlusive arterial disease with little effect in blood pressure. There are reports of increases in cutaneous blood flow and skin temperature after local application of moxisylyte.10,CC(C)C1=C(OCCN(C)C)C=C(C)C(OC(C)=O)=C1,"Moxisylyte is vasodilator that works as a specific alpha-adrenergic blocking agent. Its action is known to be competitive against norepinephrine without beta-receptor blocking, anti-angiotensin or anti-serotonin activity.TargetActionsOrganismAAlpha adrenergic receptorantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Amines', 'Autonomic Agents', 'Cardiovascular Agents', 'Cholinesterase substrates', 'Dimethylamines', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Erectile Dysfunction', 'Genito Urinary System and Sex Hormones', 'Methylamines', 'Miotics', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Peripheral Vasodilators', 'Sympatholytics', 'Urologicals', 'Vasodilating Agents']" +DB09230,Azelnidipine,"Azelnidipine is a dihydropyridine calcium channel blocker. It is marketed by Daiichi-Sankyo pharmaceuticals, Inc. in Japan. It has a gradual onset of action and produces a long-lasting decrease in blood pressure, with only a small increase in heart rate, unlike some other calcium channel blockers3. It is currently being studied for post-ischemic stroke management4.",['Q02641'],"Azelnidipine is a vasodilator that induces a gradual decrease in blood pressure in hypertensive patients. Unlike other members of its drug class, azelnidipine does not induce reflex tachycardia due to vasodilation. This is likely due to the fact that it elicits a gradual fall in blood pressureIt also exhibits a prolonged hypotensive effect and has been shown to have a strong anti-arteriosclerotic action in vessels due to its high affinity for vascular tissue and antioxidative activity2.Clinical studies have demonstrated that azelnidipine markedly reduced heart rate and proteinuria in hypertensive patients by inhibiting sympathetic nerve activity. Azelnidipine has also been confirmed to have cardio-protective, neuroprotective, and anti-atherosclerotic properties, and has also been found to prevent insulin resistance2.",CC(C)OC(=O)C1=C(C)NC(N)=C(C1C1=CC=CC(=C1)[N+]([O-])=O)C(=O)OC1CN(C1)C(C1=CC=CC=C1)C1=CC=CC=C1,"Azelnidipine inhibits trans-membrane Ca+ influx through the voltage-dependent channels of smooth muscles in vascular walls. Ca+ channels are classified into various categories, including L-type, T-type, N-type, P/Q-type, and R-type Ca+ channels. The L-type Ca+ channels. Normally, calcium induces smooth muscle contraction, contributing to hypertension. When calcium channels are blocked, the vascular smooth muscle does not contract, resulting in relaxation of vascular smooth muscle walls and decreased blood pressure.TargetActionsOrganismUVoltage-dependent L-type calcium channel subunit beta-agonistHumans",[],"['Acids, Acyclic', 'Agents causing hyperkalemia', 'Amino Acids', 'Amino Acids, Cyclic', 'Amino Acids, Peptides, and Proteins', 'Antiarrhythmic agents', 'Azetidines', 'Azetines', 'Bradycardia-Causing Agents', 'Calcium Channel Blockers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Imines', 'Imino Acids', 'Pyridines', 'Vasodilating Agents']" +DB03904,Urea,Ureais a keratolytic emollient used to treat hyperkeratotic lesions and moisturize the skin.,"['P00378', 'P05089', 'P00918', 'P35222', 'Q8XB74']","Urea is a keratolytic emollient that works to treat or prevent dry, rough, scaly, itchy skin.1",NC(N)=O,TargetActionsOrganismADihydrofolate reductaseactivatorGallus gallusUArginase-Not AvailableHumansUCarbonic anhydrase Not AvailableHumansUCatenin beta-Not AvailableHumansUSulfoxide reductase catalytic subunit YedYNot AvailableEscherichia coli O:H,['Moisturizing'],"['Amides', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Carbamide products', 'Dermatologicals', 'Diuretics, Osmotic', 'Emollients and Protectives', 'i.v. Solutions', 'Keratolytic Agents', 'Solutions Producing Osmotic Diuresis']" +DB06267,Udenafil,Udenafilis a PDE5 inhibitor used to treat erectile dysfunction.,['O76074'],Udenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor.,CCCOC1=C(C=C(C=C1)S(=O)(=O)NCCC1CCCN1C)C1=NC(=O)C2=C(N1)C(CCC)=NN2C,"Udenafil inhibits the cGMP specific phosphodiesterase type (PDE) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type (PDE) by udenafil enhances erectile function by increasing the amount of cGMP.TargetActionsOrganismAcGMP-specific ','-cyclic phosphodiesteraseinhibitorHumans",[],"['Amides', 'Benzene Derivatives', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Erectile Dysfunction', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Phosphodiesterase 5 Inhibitors', 'Phosphodiesterase Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Urologicals', 'Vasodilating Agents']" +DB13946,Testosterone undecanoate,Testosterone undecanoateis an androgen indicated for testosterone replacement therapy in adult males with primary hypogonadism and hypogonadotropic hypogonadism.,['P10275'],"Once in circulation, testosterone undecanoate is cleaved to release testosterone, which mediates a range of biological actions. Testosterone is an endogenous male hormone that plays a key role in male sexual differentiation: it is involved in the regulation of hematopoiesis, body composition, and bone metabolism. As a hormone replacement therapy, testosterone undecanoate is an exogenous source of testosterone in males with hypogonadism. Testosterone therapy aims to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, and loss of muscle and bone mass.3Testosterone has a controlled substance in the US due to the abuse potential by athletes and bodybuilders. The use of testosterone at higher doses than recommended can lead to withdrawal symptoms lasting for weeks or months. Withdrawal symptoms include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido, and hypogonadotropic hypogonadism.6Testosterone can cause hirsutism, virilization, deepening of the voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities when administered to women. The use in adolescents can lead to the premature closure of bony epiphyses with termination of growth and precocious puberty.6",CCCCCCCCCCC(=O)O[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C,"Testosterone is a critical male sex hormone that is responsible for the normal growth and development of the male sex organs and the maintenance of secondary sex characteristics, such as the growth and maturation of male sex organs, the development of male hair distribution, vocal cord thickening, and alterations in body musculature and fat distribution. Male hypogonadism, resulting from insufficient testosterone secretion, has two main etiologies: primary hypogonadism is caused by defects in the gonads, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH and LH).In the circulation, testosterone undecanoate is cleaved by endogenous non-specific esterases to release testosterone, the active component of the compound. The undecanoate side chain is pharmacologically inactive.,Testosterone can be further converted by α reductase to its more biologically active form, dihydrotestosterone (DHT). The actions of testosterone and DHT are mediated via androgen receptor, which is widely expressed in many tissues, including the bone, muscle, prostate, and adipose tissue. Testosterone binds to androgen receptors with high affinity and regulates target gene transcription involved in the normal growth and development of the male sex organs and the maintenance of secondary sex characteristics.Testosterone can cause improved sexual function, increased lean body mass, bone density, erythropoiesis, prostate size, and changes in lipid profiles.TargetActionsOrganismAAndrogen receptoragonistHumans",['Hormone Replacement Therapy'],"['Androgens', 'Androstanes', 'Androstenes', 'Androstenols', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Fused-Ring Compounds', 'Gonadal Hormones', 'Gonadal Steroid Hormones', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OAT3/SLC22A8 Inducers', 'OATP1B3 substrates', 'P-glycoprotein inhibitors', 'Steroids', 'Testosterone and derivatives', 'Testosterone Congeners', 'Thyroxine-binding globulin inhibitors']" +DB03701,Vanoxerine,Vanoxerineis an investigational dopamine transporter antagonist suggested to be beneficial in the treatment of cocaine addiction.,"['Q01959', 'Q12809', 'Q9H252', 'Q9NS40']","Vanoxerine inhibits dopamine reuptake by binding and blocking the dopamine transporter. The use of vanoxerine has been evaluated as a potential substitute of cocaine in the treatment of drug addiction.1In primates, the intravenous administration of vanoxerine reduced cocaine self-administration at 1 mg/kg and eliminated it at 3 mg/kg.1The stimulant profile of cocaine was not detected in healthy volunteers (n=8) receiving vanoxerine for 2 weeks, suggesting a lack of abuse potential of vanoxerine.1However, other studies have found that vanoxerine has at least moderate potential to be abused by humans.9The antiarrhythmic potential of vanoxerine has also been assessed. A clinical study evaluating the efficacy of vanoxerine on the conversion of atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm reported that, within 24 hours, a significant proportion of symptomatic AF/AFL patients treated with 200, 300 and 400 mg of vanoxerine converted to sinus rhythm.7In studies that evaluated doses ranging from 25 to 300 mg, vanoxerine was considered to be safe and tolerable.1,2",FC1=CC=C(C=C1)C(OCCN1CCN(CCCC2=CC=CC=C2)CC1)C1=CC=C(F)C=C1,"Vanoxerine is a highly selective dopamine transporter antagonist. Due to its ability to inhibit dopamine reuptake, it has been suggested that vanoxerine may be beneficial in treating cocaine addiction.Cocaine increases the amount of dopamine in the synapse by attaching and blocking the dopamine transporter. Compared to cocaine, vanoxerine has a higher affinity for the dopamine transporter and a slower dissociation rate, without the stimulant profile of cocaine.The use of vanoxerine to treat conditions characterized by low levels of dopamine, such as Parkinson's disease and depression, has also been investigated.Vanoxerine is also a potent blocker of the hKV. (hERG) cardiac potassium channel.Even at low concentrations, vanoxerine is capable of blocking calcium and sodium currents without having a significant effect on QT interval, action potential waveforms and transmural dispersion of repolarization.Because of this, the anti-arrhythmic and anti-atrial fibrillatory properties of vanoxerine have been investigated.,,TargetActionsOrganismASodium-dependent dopamine transporterantagonistHumansUHERG human cardiac K+ channelblockerHumans",[],"['Antiarrhythmic agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Agents', 'Dopamine Uptake Inhibitors', 'Membrane Transport Modulators', 'Neurotransmitter Agents', 'Neurotransmitter Uptake Inhibitors']" +DB01139,Cefapirin,Cefapirinis a first generation cephalosporin indicated in the treatment of susceptible bacterial infections.,['Q8XJ01'],"Cephapirin is a first-generation cephalosporin that has a wide spectrum of activity against gram-positive and gram-negative organisms. Cephapirin is more resistant to beta-lactamases than are the penicillins and so is effective against staphylococci, with the exception of methicillin-resistant staphylococci.",[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)CSC1=CC=NC=C1)C(O)=O,The bactericidal activity of cephapirin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).TargetActionsOrganismAPenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A),[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephacetrile', 'Cephalosporins', 'First-Generation Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Sulfur Compounds', 'Thiazines']" +DB00198,Oseltamivir,Oseltamiviris a neuraminidase inhibitor used in the prophylaxis and treatment of influenza.,"['P11485', 'Q99519', 'Q9Y3R4']","There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir to these events has not been established. Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.21,13,14",CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1,"Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate) which is a potent and selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface. Viral neuraminidase enzyme activity is important for viral entry into uninfected cells, for the release of recently formed virus particles from infected cells, and for the further spread of the infectious virus in the body.,,Oseltamivir activity reduces viral shedding and infectivity.Oseltamivir is effective agaisnt viral neuraminidases of influenza A (including pandemic HN) and influenza B.,,TargetActionsOrganismANeuraminidaseinhibitorInfluenza A virus (strain A/Chile// HN)USialidase-inhibitorHumansUSialidase-inhibitorHumans",[],"['Acetamides', 'Acetates', 'Amides', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Neuraminidase Inhibitors', 'OAT3/SLC22A8 Substrates']" +DB01589,Quazepam,Quazepamis a long-acting benzodiazepine used to manage insomnia.,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88', 'P14867', 'P47869', 'P34903', 'P31644', 'Q8N1C3', 'P18507', 'Q99928']","Benzodiazepines, including quazepam, exert their sedative and anxiolytic effects by potentiating the effects of endogenous GABA, the primary inhibitory neurotransmitter in the central nervous system.3",FC1=CC=CC=C1C1=NCC(=S)N(CC(F)(F)F)C2=C1C=C(Cl)C=C2,"Like other benzodiazepines, quazepam likely exerts its effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA(A) receptors, the main inhibitory neurotransmitter receptors in the mammalian brain.GABA(A) receptors are a component of GABA-gated ionotropic chloride channels that produce inhibitory postsynaptic potentials - following activation by GABA, the channel undergoes a conformational change that allows the passage of chloride ions through the channel. The inhibitory potentials produced by GABA neurotransmission play an integral role in the suppression and control of epileptiform nerve firing such as that seen in epilepsy, which makes the GABA system a desirable target in the treatment of epilepsy.Benzodiazepines are positive allosteric modulators of GABA(A) function. They bind to the interface between alpha (α) and gamma (γ) subunits on the receptor, commonly referred to as the benzodiazepine binding site, and modulate the receptor such that its inhibitory response to GABA binding is dramatically increased.TargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumansAGABA(A) Receptor Benzodiazepine Binding SiteligandHumans",[],"['Benzazepines', 'Benzodiazepine hypnotics and sedatives', 'Benzodiazepines and benzodiazepine derivatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Hypnotics and Sedatives', 'Nervous System', 'Psycholeptics']" +DB00962,Zaleplon,Zaleplonis a sedative used for short term treatment of insomnia in adults.,['P14867'],"Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zaleplon is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zaleplon also binds selectively to the CNS GABAA-receptor chloride ionophore complex at benzodiazepine(BZ) omega-1 (BZ1, ο1) receptors.",CCN(C(C)=O)C1=CC=CC(=C1)C1=CC=NC2=C(C=NN12)C#N,Zaleplon exerts its action through subunit modulation of the GABABZ receptor chloride channel macromolecular complex. Zaleplon also binds selectively to the brain omega- receptor located on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumans,[],"['Acetates', 'Acids, Acyclic', 'Amides', 'Anticonvulsants', 'Benzodiazepine hypnotics and sedatives', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Central Nervous System Depression', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'GABA Agents', 'GABA Agonists', 'GABA Modulators', 'GABA-A Receptor Agonists', 'gamma-Aminobutyric Acid A Receptor Agonist', 'Hypnotics (Nonbenzodiazepine)', 'Hypnotics and Sedatives', 'Miscellaneous Anxiolytics Sedatives and Hypnotics', 'Nervous System', 'Neurotransmitter Agents', 'Psycholeptics']" +DB05490,AMG-131,"AMG-131 (T131), an orally-administered therapy, is expected to lower blood glucose in type II diabetic patients by improving the body’s ability to respond to insulin. T131 is a selective modulator of PPARg (peroxisome proliferator activated receptor gamma), a receptor involved in regulating the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia.",['P37231'],"T131, an orally-administered therapy, is expected to lower blood glucose in type II diabetic patients by improving the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia",ClC1=CC=C(C(Cl)=C1)S(=O)(=O)NC1=CC(Cl)=C(OC2=CN=C3C=CC=CC3=C2)C(Cl)=C1,"T is a selective modulator of PPARg (peroxisome proliferator activated receptor gamma), a receptor involved in regulating the body’s ability to respond to insulin. T is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and AvandiaTargetActionsOrganismAPeroxisome proliferator-activated receptor gammapartial agonistHumans",[],"['Amides', 'Heterocyclic Compounds, Fused-Ring', 'PPAR gamma, agonists', 'Sulfones', 'Sulfur Compounds']" +DB09129,Chromic chloride,Chromic chlorideis a supplement to intravenous solutions given for total parenteral nutrition (TPN).,['P06213'],"Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Providing chromium during TPN helps prevent deficiency symptoms including impaired glucose tolerance, ataxia, peripheral neuropathy and a confusional state similar to mild/moderate hepatic encephalopathy.",[Cl-].[Cl-].[Cl-].[Cr+3],"Metallic chromium has no biological activity. Chromium is referred as a glucose tolerance factor. This glucose tolerance factor is a complex of molecules. Glycine, cysteine, glutamic acid and nicotinic acid along with chromium form this complex.TargetActionsOrganismAInsulin receptoractivatorHumans",['Total parenteral nutrition therapy'],"['Anions', 'Antioxidants', 'Biological Factors', 'Chlorine Compounds', 'Compounds used in a research, industrial, or household setting', 'Drugs that are Mainly Renally Excreted', 'Electrolytes', 'Ions', 'Minerals', 'Protective Agents', 'Replacement Preparations']" +DB06663,Pasireotide,"Pasireotideis a somatostatin analog used in the treatment of Cushing’s disease, specifically for those patients whom pituitary surgery is not appropriate.","['P30872', 'P30874', 'P32745', 'P35346']",Signifor® is an analogue of somatostatin that promotes reduced levels of cortisol secretion in Cushing's disease patients.,NCCCC[C@@H]1NC(=O)[C@@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@@H]2C[C@H](CN2C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=C(OCC3=CC=CC=C3)C=C2)NC1=O)OC(=O)NCCN)C1=CC=CC=C1,"Pasireotide activates a broad spectrum of somatostatin receptors, exhbiting a much higher binding affinity for somatostatin receptors , , and than octreotide in vitro, as well as a comparable binding affinity for somatostatin receptor . The binding and activation of the somatostatin receptors causes inhibition of ACTH secretion and results in reduced cortisol secretion in Cushing's disease patients. Also this agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.TargetActionsOrganismUSomatostatin receptor type Not AvailableHumansUSomatostatin receptor type Not AvailableHumansUSomatostatin receptor type Not AvailableHumansUSomatostatin receptor type Not AvailableHumans",[],"['Amino Acids, Peptides, and Proteins', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Hypoglycemia-Associated Agents', 'Hypothalamic Hormones', 'Nerve Tissue Proteins', 'Neuropeptides', 'Pancreatic Hormones', 'Peptide Hormones', 'Peptides', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormone Release Inhibiting Hormones', 'Potential QTc-Prolonging Agents', 'Proteins', 'QTc Prolonging Agents', 'Somatostatin Agonists', 'Somatostatin and Analogues', 'Somatostatin Receptor Agonists', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB01127,Econazole,"Econazoleis a topical antifungal used to treat tinea pedis, tinea cruris, tinea corporis, cutaneous candidiasis and tinea versicolor.","['P10613', 'O75469']","Econazole is an antifungal medication related to fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Econazole prevents fungal organisms from producing vital substances required for growth and function. This medication is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.",ClC1=CC=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1,"Econazole interacts with -α demethylase, a cytochrome P- enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Econazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.TargetActionsOrganismACytochrome P antagonistYeastUNuclear receptor subfamily group I member partial agonistHumans",[],"['14-alpha Demethylase Inhibitors', 'Anti-Infective Agents', 'Antifungal Agents', 'Antifungal Agents (Vaginal)', 'Antifungals for Dermatological Use', 'Antifungals for Topical Use', 'Azole Antifungals', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hormone Antagonists', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazole and Triazole Derivatives', 'Imidazole Derivatives', 'Imidazoles', 'P-glycoprotein inhibitors', 'Steroid Synthesis Inhibitors']" +DB08881,Vemurafenib,"Vemurafenibis a kinase inhibitor used to treat patients with Erdheim-Chester Disease who have the BRAF V600 mutation, and melanoma in patients who have the BRAF V600E mutation.",['P15056'],"BRAF activation results in cell growth, proliferation, and metastasis. BRAF is an intermediary molecule in MAPK whose activation depends on ERK activation, elevation of cyclin D1 and cellular proliferation. The mutation V600E produces a constitutively form of BRAF. Vemurafenib has been shown to reduce all activation markers related to BRAF; in clinical trials, vemurafenib treatment showed a reduction of cytoplasmic phosphorylated ERK and a cell proliferation driven by Ki-67. Studies also reported decrease in MAPK-related metabolic activity.3All the different reports indicate thet Vemurafenib generates an almost complete inhibition of the MAPK pathway.",CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=NC=C(C=C23)C2=CC=C(Cl)C=C2)=C(F)C=C1,Vemurafenib is an orally available inhibitor of mutated BRAF-serine-threonine kinase. Vemurafenif is a small molecule that interacts as a competitive inhibitor of the mutated species of BRAF. It is especially potent against the BRAF VE mutation. Vemurafenib blocks downstream processes to inhibit tumour growth and eventually trigger apoptosis. Vemurafenib does not have antitumour effects against melanoma cell lines with the wild-type BRAF mutation.TargetActionsOrganismASerine/threonine-protein kinase B-rafinhibitorHumans,[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'B-Raf serine-threonine kinase (BRAF) inhibitors', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (moderate)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'Indoles', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Tyrosine Kinase Inhibitors']" +DB01685,Topiroxostat,"Topiroxostat is a selective xanthine oxidase inhibitor developed for treatment and management of hyperuricemia and gout. Xanthine oxidase, or xanthine oxidoreductase (XOR), regulates purine metabolism, and inhibition of the enzyme results in efficacious reduction of serum urate levels. Xanthine oxidase inhibitors are classified into two groups; purine analogs such asAllopurinolandOxypurinol, and non-purine agents which includes topiroxostat. WhileAllopurinolis considered a first-line therapy in treating hyperuricemic conditions, it is often associated with side effects and ineffective in reducing uric acid levels under recommended dosing regimens. Renal complications are major comorbidities that limit theAllopurinoltherapy as dose reductions are recommended. Topiroxostat and its metabolites are shown to be unaffected by renal complications, thus may be effective in patients with chronic kidney diseases2. Approved for therapeutic use in Japan since 2013, topiroxostat is marketed under the name Topiloric and Uriadec and is orally administered twice daily.",['P47989'],"Topiroxostat reduces the synthesis of uric acid by competitively inhibiting xanthine oxidase in a selective and time-dependent manner1. It serves to reduce the concentration of insoluble urates and uric acid in tissues, plasma and urine. Topiroxostat is not reported to cause QT prolongation4.",N#CC1=NC=CC(=C1)C1=NNC(=N1)C1=CC=NC=C1,"Uric acid synthesis depends on the action of xanthine oxidase activity in the conversion of hypoxanthine to xanthine, followed by the conversion of xanthine to uric acid. Xanthine oxidase consists of a molybdenum ion as cofactor in the active center that has different redox states upon substrate binding. When a substrate such as hypoxanthine or xanthine binds, xanthine oxidase hydroxylates it and molybdenum ion is reduced from hexavalent, Mo(VI), to tetravalent form, Mo(IV). Molybdenum ion is reoxidized into hexavalent state once the hydroxylated substrate, xanthine or uric acid, dissociates from the active site. Topiroxostat is shown to interact with multiple amino acid residues of the solvent channel and additionally forms a reaction intermediate by covalent binding with molybdenum (IV) ion via an oxygen atom,,,. It also forms hydrogen bonds with molybdenum (VI) ion, suggesting that it has multiple inhibition modes to xanthine oxidase. Enhanced binding interactions to xanthine oxidase achieves delayed dissociation of topiroxostat from the enzyme. -hydroxy-topiroxostat, the metabolite formed by primary hydroxylation of topiroxostat by xanthine oxidase, also causes time and concentration-dependent inhibition of the enzyme. +Topiroxostat is shown to inhibit ATP-binding cassette transporter G (ABCG) in vitro, which is a membrane protein responsible for recovering uric acid in the kidneys and secreting uric acid from the intestines,.TargetActionsOrganismUXanthine dehydrogenase/oxidaseNot AvailableHumans",[],"['BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'UGT1A9 Substrates']" +DB01000,Cyclacillin,A cyclohexylamido analog of penicillanic acid.,"['Q8DR59', 'Q75Y35', 'C1KC03', 'P0AEB2', 'P24228', 'P08506', 'P02918', 'P02919', 'P0AD65', 'P0AD68']","Cyclacillin, a penicillin, is a cyclohexylamido analog of penicillanic acid. Cyclacillin is more resistant to beta-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin has been replaced by newer penicillin treatments.",[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1(N)CCCCC1)C(O)=O,"The bactericidal activity of cyclacillin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cyclacillin is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.TargetActionsOrganismAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin binding protein ainhibitorStaphylococcus aureusAPenicillin-binding proteininhibitorGram positive and gram negative bacteria",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Sulfur Compounds']" +DB00689,Cephaloglycin,A cephalorsporin antibiotic that is no longer commonly used.,['P02919'],Cephaloglycin is an antibiotic related to cephalosporin but no longer in common use. It is an orally absorbed derivative of cephalosporin C.,[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(O)=O,The bactericidal activity of cephaloglycin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).TargetActionsOrganismAPenicillin-binding protein BantagonistEscherichia coli (strain K),[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Sulfur Compounds', 'Thiazines']" +DB09147,Ferric pyrophosphate,Ferric pyrophosphate is an iron replacement product. Free iron presents several side effects as it can catalyze free radical formation and lipid peroxidation as well as the presence of interactions of iron in plasma. The ferric ion is strongly complexed by pyrophosphate.1It presents an increasing interest as this insoluble form can be milder in the gastrointestinal tract and present higher bioavailability.10,"['P02792', 'P69905', 'P68871']","Iron supplementation typically results in increases in serum iron, transferrin-bound iron, and iron-stored in the form of ferritin in hepatocytes and macrophages. The available iron is usually used in bone marrow for the synthesis of hemoglobin.9",[Fe+3].[Fe+3].[Fe+3].[Fe+3].[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O,"The usage of ferric pyrophosphate is based on the strong complex formation between these two species. Besides, the capacity of pyrophosphate to trigger iron removal from transferrin, enhance iron transfer from transferrin to ferritin and promote iron exchange between transferrin molecules. These properties make it a very suitable compound for parenteral administration, iron delivery into circulation and incorporation into hemoglobin.TargetActionsOrganismAFerritin light chainbinderHumansAHemoglobin subunit alphabinderHumansAHemoglobin subunit betabinderHumans",['Iron replacement therapy'],"['Acids', 'Acids, Noncarboxylic', 'Anions', 'Electrolytes', 'Elements', 'Ions', 'Iron Compounds', 'Metals', 'Metals, Heavy', 'Parenteral Iron Replacement', 'Phosphate salts', 'Phosphoric Acids', 'Phosphorus Acids', 'Phosphorus Compounds', 'Polyphosphates', 'Transition Elements']" +DB04892,Phenserine,"Phenserine is under development by Axonyx, a US biopharmaceutical company that focuses on treatments for dementia. Phenserine is a next generation acetylcholinesterase (AChE) inhibitor indicated for the treatment of AD. Unlike currently marketed AChE inhibitors, it has a dual mechanism of action that also includes anti-amyloid activity, which may confer disease-modifying effects in patients with AD. If this is substantiated in an ongoing clinical trial then phenserine may open the door to an entirely new type of treatment for AD. Axonyx announced on 20 September 2005 that phenserine was ineffective in two curtailed phase 3 trials.","['P06276', 'P05067', 'P22303']","Phenserine, a phenylcarbamate of physostigmine, is a reversible acetyl-selective cholinesterase inhibitor. In studies of rats with lesions of the forebrain cholinergic system, injections of phenserine was found to significantly decrease the levels of secreted beta-APP in the CSF of the rats. A study on cultured human brain cells found that phenserine reduces Abeta levels by regulating beta-APP translation.",[H][C@]12N(C)CC[C@@]1(C)C1=C(C=CC(OC(=O)NC3=CC=CC=C3)=C1)N2C,"Phenserine is a highly selective, reversible acetylcholinesterase inhibitor, a mechanism of action known to improve memory and cognition in Alzheimer’s subjects. Phenserine may prove to concentrate in the brain rapidly which would reduce the incidence of drug toxicity and side effects.TargetActionsOrganismUCholinesteraseinhibitorHumansUAmyloid beta A proteinNot AvailableHumansUAcetylcholinesteraseNot AvailableHumans",[],"['Acids, Acyclic', 'Alkaloids', 'Carbamates', 'Cholinergic Agents', 'Cholinesterase Inhibitors', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Neurotransmitter Agents', 'Phenylcarbamates', 'Stereoisomerism']" +DB09031,Miltefosine,"Miltefosineis an antileishmanial agent used to treat leishmaniasis, a group of disease caused by parasites of the Leishmania type.",['P08183'],Little is known about the clinical pharmacodynamics of miltefosine and other antileishmanial drugs.,CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C,"Miltefosine has demonstrated activity against Leishmania parasites and neoplastic cells primarily due to its effects on apoptosis and disturbance of lipid-dependent cell signalling pathways. Several potential antileishmanial mechanisms of action have been proposed, however no mechanism has been identified definitely. Within the mitochondria, miltefosine inhibits cytochrome-c oxidase leading to mitochondrial dysfunction and apoptosis-like cell death. Antineoplastic mechanisms of action are related to antileishmanial targets and include inhibition of phosphatidylcholine biosynthesis and inhibition of Akt (also known as protein kinase B), which is a crucial protein within the PIK/Akt/mTOR intracellular signalling pathway involved in regulating the cell cycle. Animal studies also suggest it may be effective against Trypanosome cruzi (the organism responsible for Chagas' disease), metronidazole-resistant strains of Trichonomas vaginalis, and it may have broad-spectrum anti-fungal activity.TargetActionsOrganismUP-glycoprotein Not AvailableHumans",[],"['Agents Against Leishmaniasis and Trypanosomiasis', 'Amines', 'Anti-Infective Agents', 'Antifungal Agents', 'Antileishmanial', 'Antineoplastic Agents', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Onium Compounds', 'Quaternary Ammonium Compounds', 'Trimethyl Ammonium Compounds']" +DB09053,Ibrutinib,"Ibrutinibis an antineoplastic agent used to treat chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia.",['Q06187'],"In vitro studies have shown an induction of CLL cell apoptosis even in presence of prosurvival factors. It has also been reported an inhibition of CLL cell survival and proliferation as well as an impaired in cell migration and a reduction in the secretion of chemokines such as CCL3 and CCL4. The latter effect has been shown to produce regression in xenograft mouse models.6Clinical studies for relapsed/refractory CLL in phase I and II showed an approximate 71% of overall response rate.7,8. In the case of relapsed/refractory mantle cell lymphoma, approximately 70% of the tested patients presented a partial or complete response.7,9. In clinical trials for relapsed/refractory diffuse large B-cell lymphoma, a partial response was found in between 15-20% of the patients studied; while for patients with relapsed/refractory Waldenstrom's macroglobulinemia, a partial response was observed in over 75% of the patients tested. Finally, for patients with relapsed/refractory follicular lymphoma, a partial to complete response was obtained in approximately 54% of the patients.7",NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1,"Ibrutinib is an inhibitor of Bruton’s tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue in the active site of BTK (Cys), leading to its inhibition. The inhibition of BTK plays a role in the B-cell receptor signaling and thus, the presence of ibrutinib prevents the phosphorylation of downstream substrates such as PLC-γ.TargetActionsOrganismATyrosine-protein kinase BTKinhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', ""Bruton's tyrosine kinase (BTK) inhibitors"", 'Cancer immunotherapy', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Immunotherapy', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'Protein Kinase Inhibitors', 'Purines', 'Tyrosine Kinase Inhibitors']" +DB04335,Inosine,Inosineis a nutritional supplement touted to improve athletic performance and a drug used in vitro as a red blood cell rejuvenator for a unit of red blood cells that will be used in a clinical setting.,"['P00491', 'Q9GPQ4', 'P0ABP8']","Inosine may have neuroprotective, cardioprotective, anti-inflammatory and immunomodulatory activities.",OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1NC=NC2=O,"Inosine has been found to have potent axon-promoting effects in vivo following unilateral transection of the corticospinal tract of rats. The mechanism of this action is unclear. Possibilities include serving as an agonist of a nerve growth factor-activated protein kinase (N-Kinase), conversion to cyclic nucleotides that enable advancing nerve endings to overcome the inhibitory effects of myelin, stimulation of differentiation in rat sympathetic neurons, augmentation of nerve growth factor-induced neuritogenesis and promotion of the survival of astrocytes, among others. The mechanism of inosine's possible cardioprotective effect is similarly unclear. Inosine has been reported to have a positive inotropic effect and also to have mild coronary vasodilation activity. Exogenous inosine may contribute to the high-energy phosphate pool of cardiac muscle cells and favorably affect bioenergetics generally. Inosine has also been reported to enhance the myocardial uptake of carbohydrates relative to free fatty acids as well as glycolysis. In cell culture studies, inosine has been found to inhibit the production, in immunostimulated macrophages and spleen cells, of the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-, interleukin (IL)-, macrophage-inflammatory protein- alpha and interferon (IFN)-gamma. It also suppressed proinflammatory cytokine production and mortality in a mouse endotoxemic model. These actions might account for the possible immunomodulatory, anti-inflammatory and anti-ischemic actions of inosine.TargetActionsOrganismUPurine nucleoside phosphorylaseNot AvailableHumansUIAG-nucleoside hydrolaseNot AvailableTrypanosoma vivaxUPurine nucleoside phosphorylase DeoD-typeNot AvailableEscherichia coli (strain K)",['Rejuvenation of a unit of RBC'],"['Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Ophthalmologicals', 'Purine Nucleosides', 'Purines', 'Ribonucleosides', 'Sensory Organs']" +DB01608,Periciazine,"Periciazineis a phenothiazine used with other medications to treat aggressiveness, impulsiveness, and hostility associated with psychiatric conditions such as schizophrenia.","['P21728', 'P08913', 'P35368', 'P10275']","Pericyazine is a phenothiazine of the piperidine group. It has been shown to reduce pathologic arousal and affective tension in some psychotic patients, while the symptoms of abnormal mental integration are relatively unaffected. It is a sedative phenothiazine with weak antipsychotic properties. It also has adrenolytic, anticholinergic, metabolic and endocrine effects, and an action on the extrapyramidal system.",OC1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(C=C3)C#N)CC1,"Pericyazine, like other phenothiazines, is presumed to act principally in the subcortical areas, by producing what has been described as a central adrenergic blockade of the alpha adrenergic receptors as well as antagonism of the D() dopamine receptor.TargetActionsOrganismADopamine D receptorantagonistHumansAAlpha-A adrenergic receptorantagonistHumansUAlpha-B adrenergic receptorantagonistHumansUAndrogen receptorNot AvailableHumans",[],"['Adrenergic alpha-1 Receptor Antagonists', 'Adrenergic alpha-Antagonists', 'Adrenergic Antagonists', 'Agents that produce hypertension', 'Antipsychotic Agents', 'Antipsychotic Agents (First Generation [Typical])', 'Central Nervous System Depressants', 'Dopamine Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Neurotoxic agents', 'Phenothiazines', 'Phenothiazines With Piperidine Structure', 'Psycholeptics', 'Sulfur Compounds']" +DB00340,Metixene,Metixene (or methixene) is a anticholinergic used as an antiparkinsonian agent.,"['P11229', 'P08172', 'P20309', 'P08173', 'P08912']","Metixene is a tertiary antimuscarinic with actions similar to those of atropine; it also has antihistaminic and direct antispasmodic properties. It is used for the symptomatic treatment of parkinsonism, including the alleviation of the extrapyramidal syndrome induced by other drugs such as phenothiazines, but, like other antimuscarinics, it is of no value against tardive dyskinesias. Metixene has been discontinued.",CN1CCCC(CC2C3=CC=CC=C3SC3=CC=CC=C23)C1,"Parkinsonism is thought to result from an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the corpus striatum. The mechanism of action of centrally active anticholinergic drugs such as metixene is considered to relate to competitive antagonism of acetylcholine at muscarinic receptors in the corpus striatum, which then restores the balance.TargetActionsOrganismAMuscarinic acetylcholine receptorantagonistHumans",[],"['Agents producing tachycardia', 'Anti-Parkinson Drugs', 'Anticholinergic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Nervous System', 'Sulfur Compounds', 'Tertiary Amines', 'Xanthenes']" +DB01180,Rescinnamine,Rescinnamine is an angiotensin-converting enzyme inhibitor used as an antihypertensive drug. It is an alkaloid obtained fromRauwolfia serpentinaand other species ofRauwolfia.,['P12821'],"Used to treat hypertension. Rescinnamine inhibits angiotensin-converting enzyme. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex and general vasoconstriction, both of which lead to increases vascular resistance. By inhibiting angiotensin II, aldosterone reabsorption is decreased as well as vasoconstriction. This combined effect serves to decrease blood pressure.",[H][C@]12C[C@@H](OC(=O)C=CC3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=C3C=CC(OC)=C1)C2,"Rescinnamine Binds to and inhibits the angiotensin converting enzyme. Rescinnamine competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion.TargetActionsOrganismAAngiotensin-converting enzymeinhibitorHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing angioedema', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Alkaloids', 'Angiotensin-Converting Enzyme Inhibitors', 'Antiadrenergic Agents, Centrally Acting', 'Antihypertensive Agents', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Secologanin Tryptamine Alkaloids']" +DB00216,Eletriptan,Eletriptanis a triptan used for the treatment of migraines.,"['P28221', 'P28222', 'P30939', 'P08908']","Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist. In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat.",CN1CCC[C@@H]1CC1=CNC2=C1C=C(CCS(=O)(=O)C1=CC=CC=C1)C=C2,"Eletriptan binds with high affinity to -HTB, -HTD and -HTF receptors, has modest affinity for -HTA, -HTE, -HTB and -HT receptors, and little or no affinity for -HTA, -HTC, -HT, -HT, -HTA and -HT receptors. In contrast, eletriptan displays insignificant pharmacological activity at adrenergic alpha, alpha, or beta; dopaminergic D or D; muscarinic; or opioid receptors. While the full mechanism of action of -HT receptor agonists in relieving migrains is not fully elucidated, it is proposed that the activation of -HT receptors located on intracranial blood vessels leads to vasoconstriction that correlates with the relief of migraine headaches. It is also proposed that the activation of -HT receptors on sensory nerve endings in the trigeminal system leads to the inhibition of release of pro-inflammatory neuropeptides.TargetActionsOrganismA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor BagonistHumansA-hydroxytryptamine receptor FagonistHumansU-hydroxytryptamine receptor AagonistHumans",[],"['Agents that produce hypertension', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Biogenic Amines', 'Biogenic Monoamines', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2A6 Inducers', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Nervous System', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Triptans']" +DB00383,Oxyphencyclimine,Oxyphencyclimineis a drug used to treat smooth muscle spasticity.,"['P20309', 'P11229', 'P08172']","Oxyphencyclimine is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Oxyphencyclimine is an antimuscarinic, anticholinergic drug.",CN1CCCN=C1COC(=O)C(O)(C1CCCCC1)C1=CC=CC=C1,"Oxyphencyclimine binds the muscarinic acetylcholine receptor. It may block all three types of muscarinic receptors including M- receptors in the CNS and ganglia, M- receptors in the heart (vagus) and M- receptors at the parasympathetic NEJ system. The muscarinic acetylcholine receptors mediate various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Oxphencyclimine inhibits vagally mediated reflexes by antagonizing the action of acetylcholine. This in turn reduces the secretion of gastric acids in the stomach.TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Anticholinergic Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Muscarinic Antagonists', 'Synthetic Anticholinergics, Esters With Tertiary Amino Group']" +DB00251,Terconazole,Terconazoleis an antifungal drug used in the treatment of vulvovaginal candidiasis.,['P10613'],"Terconazole is a triazole antifungal agent available for intravaginal use. It is structurally related to imidazole-derivative antifungal agents, although terconazole and other triazoles have 3 nitrogens in the azole ring. By inhibiting the 14-alpha-demethylase (lanosterol 14-alpha-demethylase), Terconazole inhibits ergosterol synthesis. Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth.",CC(C)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1,"Terconazole may exert its antifungal activity by disrupting normal fungal cell membrane permeability. Terconazole and other triazole antifungal agents inhibit cytochrome P -alpha-demethylase in susceptible fungi, which leads to the accumulation of lanosterol and other methylated sterols and a decrease in ergosterol concentration. Depletion of ergosterol in the membrane disrupts the structure and function of the fungal cell leading to a decrease or inhibition of fungal growth.TargetActionsOrganismACytochrome P antagonistYeast",[],"['Anti-Infective Agents', 'Antifungal Agents', 'Antifungal Agents (Vaginal)', 'Azole Antifungals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Triazole Derivatives']" +DB00902,Methdilazine,Methdilazine is a phenothiazine compound with antihistaminic activity. It is used in the treatment of various dermatoses to relieve pruritus.,['P35367'],"In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Methdilazine is a histamine H1antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.",CN1CCC(CN2C3=CC=CC=C3SC3=CC=CC=C23)C1,"Methdilazine binds to the histamine Hreceptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Agents that reduce seizure threshold', 'Antihistamines for Systemic Use', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Phenothiazine Derivatives', 'Sulfur Compounds']" +DB09215,Droxicam,Droxicam is an oxicam non-steroidal anti-inflammatory drug and a prodrug ofPiroxicam. It is used to reduce pain and inflammation in musculoskeletal disorders such as rheumatoid arthritis and osteoarthritis.,"['P23219', 'P35354']","Droxicam is a prodrug ofPiroxicam1. Droxicam administration produces anti-inflammatory, antirheumatic, analgesic, and antipyretic effects similar toPiroxicam.",CN1C2=C(OC(=O)N(C2=O)C2=CC=CC=N2)C2=CC=CC=C2S1(=O)=O,Droxicam is converted toPiroxicamvia hydrolysis of the ester group in the intestine. Droxicam administration inhibits the synthesis of prostaglandins by cyclooxygenase enzymes.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumans,[],"['Agents causing hyperkalemia', 'Agents that produce hypertension', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antirheumatic Agents', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Oxicams', 'Peripheral Nervous System Agents', 'Sensory System Agents']" +DB00932,Tipranavir,Tipranaviris a protease inhibitor used to treat HIV-1 resistant to more than 1 protease inhibitor.,['Q72874'],Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.,[H][C@@](CC)(C1=CC(NS(=O)(=O)C2=NC=C(C=C2)C(F)(F)F)=CC=C1)C1=C(O)C[C@@](CCC)(CCC2=CC=CC=C2)OC1=O,"Tipranavir (TPV) is a non-peptidic HIV- protease inhibitor that inhibits the processing of the viral Gag and Gag-Pol polyproteins in HIV- infected cells, thus preventing formation of mature virions. Two mechanisms are suggested in regards to the potency of tipranavir: . Tipravanir may bind to the active site of the protease enzyme with fewer hydrogen bonds than peptidic protease inhibitors, which results in increased flexibility, allowing it to fit into the active site of the enzyme in viruses that have become resistance to other protease inhibitors. This also enables tipranavir to adjust to amino acid substitutions at the active site. . Tipranavir's strong hydrogen bonding interaction with the amide backbone of the protease active site Asp may lead to its activity against resistant viruses.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Amides', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'BSEP/ABCB11 Inhibitors', 'BSEP/ABCB11 Substrates', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hepatotoxic Agents', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Protease Inhibitors', 'Pyrans', 'Sulfones', 'Sulfur Compounds', 'UGT1A1 Inducers']" +DB12831,Gabexate,Gabexateis a protease inhibitor indicated in the treatment of acute pancreatitis.,"['P03952', 'P00734', 'P00747']",Gabexate bind and inhibits serine proteases in the coagulation cascade to prevent blood clotting.3It also prevents proteolytic destruction of IkappaB resulting in suppression of the nuclear factor kappa-B signalling pathway.1Ultimately this decreases the production of inflammatory cytokines such as tumor necrosis factor alpha which are produced as a result of NFkappaB activation.,CCOC(=O)C1=CC=C(OC(=O)CCCCCNC(N)=N)C=C1,"Gabexate inhibits kallikrein, plasmin, and thrombin by binding to their active sites.,The inhibition of these components of the coagulation cascade ultimately prevents the formation of fibrin which must be present and polymerized to form a clot. Gabexate decreases the production of inflammatory cytokines by attenuating NFkappaB and c-Jun N-terminal kinase (JNK) pathway activity.The exact mechanism for this is unknown but it is thought that gabexate prevents the proteolyytic destruction of IkappaB which deactivates NFkappaB and interferes with activator protein binding to DNA.TargetActionsOrganismAPlasma kallikreininhibitorHumansAProthrombininhibitorHumansAPlasminogeninhibitorHumans",[],"['Amidines', 'Anticoagulants', 'Enzyme Inhibitors', 'Guanidines', 'Hematologic Agents', 'Protease Inhibitors', 'Serine Protease Inhibitors']" +DB01433,Methadyl acetate,A narcotic analgesic with a long onset and duration of action. It is used mainly in the treatment of narcotic dependence.,['P35372'],Methadyl Acetate is a narcotic analgesic with a long onset and duration of action. The drug decreases a patients opioid use by preventing opioid withdrawal and in how it can mimic some of the effects of opioids.,CCC(OC(C)=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1,Methadyl Acetate is primarily a mu-type opioid receptor agonist. It functions similarily to methadone.TargetActionsOrganismAMu-type opioid receptoragonistHumans,[],"['Analgesics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Ketones', 'Narcotics', 'Opioids', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB05223,Pracinostat,"Pracinostat is a novel HDAC inhibitor with improved in vivo properties compared to other HDAC inhibitors currently in clinical trials, allowing oral dosing. Data demonstrate that Pracinostat is a potent and effective anti-tumor drug with potential as an oral therapy for a variety of human hematological and solid tumors.","['Q13547', 'Q92769', 'O15379', 'Q9UBN7']","SB939 is a novel compound with superior pharmaceutical, metabolic and pharmacokinetic properties. SB939 has demonstrated excellent in vivo anti-tumour activity in various animal models with dose proportional pharmacodynamic effects. The pharmacokinetics and pharmacodynamic attributes of SB939 explain and differentiate it as the best in class HDAC inhibitor.",CCCCC1=NC2=C(C=CC(\C=C\C(=O)NO)=C2)N1CCN(CC)CC,"Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, SB causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of SB has not been fully characterized.TargetActionsOrganismUHistone deacetylase Not AvailableHumansUHistone deacetylase Not AvailableHumansUHistone deacetylase Not AvailableHumansUHistone deacetylase Not AvailableHumans",[],"['Antineoplastic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Histone Deacetylase Inhibitors', 'Moderate Risk QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB05015,Belinostat,Belinostatis a histone deacetylase (HDAC) inhibitor used for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).,"['Q13547', 'Q969S8', 'Q96DB2', 'Q92769', 'O15379', 'P56524', 'Q9UQL6', 'Q9UBN7', 'Q8WUI4', 'Q9BY41', 'Q9UKV0']","Beleodaq is a histone deacetylase (HDAC) inhibitor that exhibits pan-HDAC inhibition and potent growth inhibitory and pro-apoptotic activities in a variety of tumor cells, including PTCL cells, at nanomolar concentrations2. None of the trials show any clinically relevant changes caused by Beleodaq on heart rate, PR duration or QRS duration as measures of autonomic state, atrio-ventricular conduction or depolarization; there were no cases of Torsades de Pointes.",ONC(=O)\C=C\C1=CC=CC(=C1)S(=O)(=O)NC1=CC=CC=C1,"Belinostat inhibits the activity of histone deacetylase (HDAC) thus prevents the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, increased the expression of tumor-suppressor genes. It ultimately induces cell cycle arrest, inhibition of angiogenesis and/or apoptosis of some transformed cells.TargetActionsOrganismAHistone deacetylaseinhibitorHumans",[],"['Amides', 'Amines', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cancer immunotherapy', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (weak)', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Histone deacetylase (HDAC) inhibitors', 'Histone Deacetylase Inhibitors', 'Hydroxy Acids', 'Hydroxylamines', 'Immunosuppressive Agents', 'Immunotherapy', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Sulfones', 'Sulfur Compounds', 'UGT1A1 Substrates', 'UGT1A1 Substrates with a Narrow Therapeutic Index']" +DB00365,Grepafloxacin,Grepafloxacinis a fluoroquinolone antibiotic used to treat various gram positive and gram negative bacterial infections.,"['P43700', 'P43702']","Grepafloxacin has in vitro activity against a wide range of gram-positive and gram-negative aerobic microorganisms, as well as some atypical microorganisms.",CC1CN(CCN1)C1=C(F)C(C)=C2C(=O)C(=CN(C3CC3)C2=C1)C(O)=O,"Grepafloxacin exerts its antibacterial activity by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, essential enzymes for duplication, transcription, and repair of bacterial DNA.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Highest Risk QTc-Prolonging Agents', 'OAT1/SLC22A6 Substrates', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'QTc Prolonging Agents', 'Quinolines', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB08903,Bedaquiline,Bedaquilineis a diarylquinoline antimycobacterial used in combination with other antibacterials to treat pulmonary multidrug resistant tuberculosis (MDR-TB).,['P9WPS1'],"Bedaquiline is primarily subjected to oxidative metabolism leading to the formation of N-monodesmethyl metabolite (M2). M2 is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (4-fold to 6-fold lower) than the parent compound. However, M2 plasma concentrations appeared to correlate with QT prolongation.6Bedaquiline inhibits mycobacterial TB at a minimal inhibitory concentration (MIC) from 0.002-0.06 μg/ml and with a MIC50of 0.03 μg/ml. The proportion of naturally resistant bacteria is low, estimated to be in one strain over 107/108bacteria. Bacteria that have smaller ATP stores (such as dormant, nonreplicating bacilli) are more susceptible to bedaquiline.1Additionally, bedaquiline is also effective against nontuberculous mycobacteria, with MICs ranging from 0.06 to 0.5 μg/ml.1A potential for the development of resistance to bedaquiline in M. tuberculosis exists. Modification of the atpE target gene, and/or upregulation of the MmpS5-MmpL5 efflux pump (Rv0678 mutations) have been associated with increased bedaquiline MIC values in isolates of M. tuberculosis. Target-based mutations generated in preclinical studies lead to 8- to 133-fold increases in bedaquiline MIC, resulting in MICs ranging from 0.25 to 4 micrograms per mL. Efflux-based mutations have been seen in preclinical and clinical isolates. These lead to 2- to 8-fold increases in bedaquiline MICs, resulting in bedaquiline MICs ranging from 0.25 to 0.5 micrograms per mL.6",COC1=NC2=C(C=C(Br)C=C2)C=C1[C@@H](C1=CC=CC=C1)[C@@](O)(CCN(C)C)C1=CC=CC2=C1C=CC=C2,"Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits mycobacterial ATP (adenosine '-triphosphate) synthase, by binding to subunit c of the enzyme that is essential for the generation of energy inM. tuberculosis..TargetActionsOrganismAATP synthase subunit cinhibitorMycobacterium tuberculosis",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Diarylquinoline Antimycobacterial', 'Drugs for Treatment of Tuberculosis', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quinolines']" +DB11828,Neratinib,Neratinibis a protein kinase inhibitor used to treat breast cancer that over expresses the HER2 receptor.,['P00533'],"Neratinib is a tyrosine kinase inhibitor which exhibits antitumor action against Epidermal Growth Factor Receptor (EGFR), HER2, and Human Epidermal Growth Factor Receptor 4 (HER4) postive carcinomas [FDA Label].",CCOC1=C(NC(=O)\C=C\CN(C)C)C=C2C(NC3=CC=C(OCC4=CC=CC=N4)C(Cl)=C3)=C(C=NC2=C1)C#N,"Neratinib binds to and irreversibly inhibits EGFR, HER, and HER [FDA Label]. This prevents auotphoshorylation of tyrosine residues on the receptor and reduces oncogenic signalling through the mitogen-activated protein kinase and Akt pathways.TargetActionsOrganismAEpidermal growth factor receptorinhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'P-glycoprotein inhibitors', 'Protein Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB04865,Omacetaxine mepesuccinate,Omacetaxine mepesuccinateis a cephalotaxine used in the treatment of Chronic Myeloid Leukemia (CML) that is intolerant to or resistant to two or more tyrosine kinase inhibitors.,"['P20276', 'P39023']","The pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involved +with protein synthesis inhibition and this leads to its antineoplastic activity.",[H][C@@]1(OC(=O)[C@@](O)(CCCC(C)(C)O)CC(=O)OC)C(OC)=C[C@]23CCCN2CCC2=CC4=C(OCO4)C=C2[C@]13[H],"Homoharringtonine inhibits protein synthesis by not directly binding to Bcr-Abl. It binds to the A-site cleft in the large ribosomal subunit, which affects chain elongation and prevents protein synthesis.TargetActionsOrganismAS ribosomal protein LantagonistHaloarcula marismortui (strain ATCC / DSM / JCM / VKM B-)AS ribosomal protein LantagonistHumans",[],"['Alkaloids', 'Antineoplastic Agents', 'Antineoplastic Agents, Phytogenic', 'Antineoplastic and Immunomodulating Agents', 'Benzazepines', 'Enzyme Inhibitors', 'Harringtonines', 'Heterocyclic Compounds, Fused-Ring', 'Narrow Therapeutic Index Drugs', 'Protein Synthesis Inhibitors']" +DB11697,Pacritinib,Pacritinibis a kinase inhibitor used for the treatment of primary and secondary myelofibrosis in adult patients with significantly reduced platelet counts.,"['O60674', 'P36888']","Pacritinib is administered orally twice daily, with or without food. It should not be used in patients with moderate or severe (Child-Pugh B or C) hepatic impairment, nor in patients with significant renal impairment (eGFR <30 mL/min).2Patients taking pacritinib may experience a prolonged QTc interval - while no cases of torsades de pointes have been reported in clinical trials, QTc prolongations to >500 msec and/or increases in baseline QTc by >60 msec were observed in some patients during clinical trials.2A baseline QTc interval should be obtained prior to initiating therapy and regular monitoring (including for risk factors, e.g. hypokalemia) should continue throughout therapy.",C(CN1CCCC1)OC1=CC=C2NC3=NC=CC(=N3)C3=CC(COC\C=C\COCC1=C2)=CC=C3,"While the pathogenesis of myelofibrosis (MF) is still poorly understood, both primary and secondary (i.e. post-polycythemia vera or post-essential thrombocythemia) myelofibrosis have been associated with mutations ofJAK.Signaling pathways initiated by JAK generate a number of cytokines and growth factors responsible for hematopoiesis and immune functioning, and its dysregulation is thought to be a driver of MF pathogenesis.Pacritinib is thought to exert its pharmacologic activity via inhibition of wild-type JAK, mutant JAKVF, and FMS-like tyrosine kinase (FLT).It has a greater inhibitory potency towards JAK than related proteins (e.g. JAK, TYK), and does not inhibit JAK at clinically relevant concentrations.Pacritinib also exhibits some inhibitory activity against other cellular kinases (e.g. CSFR and IRAK), although the clinical significance of this activity is unknown.TargetActionsOrganismATyrosine-protein kinase JAKinhibitorHumansAReceptor-type tyrosine-protein kinase FLTinhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Janus Kinase 2, antagonists & inhibitors', 'Janus Kinase Inhibitor', 'Janus Kinases, antagonists & inhibitors', 'Kinase Inhibitor', 'OCT1 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'Potential QTc-Prolonging Agents', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Tyrosine Kinase Inhibitors']" +DB06813,Pralatrexate,Pralatrexateis an antineoplastic agent used for the treatment of relapsed or refractory peripheral T-cell lymphoma.,"['P00374', 'P04818', 'Q05932']","Pralatrexate is a folate analog that inhibits folate metabolism, thus impeding the synthesis of amino acids and nucleic acid.9Additionally, pralatrexate also competes for enzymatic processing by folyopolyglutamate synthase (FPGS)with folate to increase cellular retention.9Compared to methotrexate, pralatrexate binds to the reduced folate carrier protein-1 (RFC-1) for cellular uptake with 10-times the affinity and is a more potent substrate for FPGS.10The Kmvalue for RFC-1 was calculated to be 0.3 μmol/L and 4.8 μmol/L for pralatrexate and methotrexate respectively, while the Kmvalue for FPGS was estimated to be 5.9 and 32.3 µmol/l for pralatrexate and methotrexate respectively10. As a result, pralatrexate is more cytotoxic and better retained in cancer cells.10Due to its anti-folate activity, pralatrexate's main toxicity is manifested as mucositis that can require dose interruption or reduction10,13. In 5 patients with non-small-cell lung carcinoma receiving a supratherapeutic dose of 230 mg/m2, the mean change from pre-injection QTcF interval at the end of infusion was 6.1 ms (90%CI: -0.6, 12.7), and at 1-hour post-injection was 7.8 ms (90%CI: 3.0, 12.6).13However, no patient exceeded a QTcF of 470 msec and exhibited an absolute increase from baseline in QTcF exceeding 30 msec.13As well, the study dose far exceeded the target dose for patients with peripheral T-cell lymphoma and pralatrexate does not inhibit the human ether-a-go-go-related gene (hERG) K+channel13. Therefore, pralatrexate uses are unlikely to cause cardiac repolarization delays.9,13.",NC1=NC2=NC=C(CC(CC#C)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N=C2C(N)=N1,"Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase (DHFR) selectively in cancer cells overexpressing the reduced folate carrier protein- (RFC-).Folate is a water-soluble vitamin required for DNA synthesis and maintenance as well as DNA, RNA, and protein methylation. As cancer cells are rapidly replicating, they require a lot of folates to accommodate an accelerated cell division and DNA and protein modification for cellular transformation.,Therefore, interruption with folate metabolism can inhibit tumor growth.Additionally, pralatrexate also undergoes polyglutamylation catalyzed by folyopolyglutamate synthase (FPGS).This reaction both increases cellular retention of pralatrexate for extended drug action and impedes the uptake of folate, also a substrate of FPGS, to further inhibit folate metabolism in cancer cells.TargetActionsOrganismADihydrofolate reductasesubstrateinhibitorHumansUThymidylate synthasesubstrateinhibitorHumansAFolylpolyglutamate synthase, mitochondrialsubstrateHumans",[],"['Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Drugs that are Mainly Renally Excreted', 'Folic Acid Analogues', 'Folic Acid Antagonists', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B3 substrates', 'Pteridines', 'Pterins']" +DB04938,Ospemifene,"Ospemifeneis a non-hormonal estrogen receptor modulator (SERM) used to treat moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.",['P03372'],"The half maximal inhibitory concentration (IC50) for estrogen receptor (ER) alpha and beta are 0.8 μM and 1.7 μM, respectively. Ospemifene has potential uses in the management of osteoporosis in postmenopausal women. It interacts with osteoblasts and osteoclasts in such a way that it reduces bone turnover. It also has potential uses in the prevention of breast cancer. Studies suggest that ospemifene, in a dose-dependent manner, reduces the incidence of tumours.",OCCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1,Ospemifene is a next generation SERM (selective estrogen receptor modulator) that selectively binds to estrogen receptors and either stimulates or blocks estrogen's activity in different tissue types. It has an agonistic effect on the endometrium.TargetActionsOrganismAEstrogen receptor alphaantagonistagonistHumans,[],"['Benzene Derivatives', 'Benzylidene Compounds', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Estrogen Agonist-antagonists', 'Estrogen Agonist/Antagonist', 'Genito Urinary System and Sex Hormones', 'Selective Estrogen Receptor Modulators', 'Sex Hormones and Modulators of the Genital System', 'Stilbenes']" +DB08912,Dabrafenib,"Dabrafenibis a kinase inhibitor used to treat patients with specific types of melanoma, non-small cell lung cancer, and thyroid cancer.","['P15056', 'P04049', 'P57059', 'Q8NG66', 'P53667']","Dabrafenib is a kinase inhibitor that is mainly used to target BRAF V600E mutation in multiple types of cancer. Although dabrafenib andtrametinibboth inhibit the RAS/RAF/MEK/ERK pathway, they inhibit different effectors of the pathway, thus increasing response rate and mitigating resistance without cumulative toxicity.11The melanoma approval for use withtrametinibis based on results from COMBI-AD, a Phase III study of 870 patients with Stage III BRAF V600E/K mutation-positive melanoma treated with dabrafenib + trametinib after complete surgical resection. Patients received doses of dabrafenib (150 mg BID) + trametinib (2 mg QD) combination (n = 438) or matching placebos (n = 432). After a median follow-up of 2.8 years, the primary endpoint of relapse-free survival (RFS) was met.16In the case of thyroid cancer, Dabrafenib plus Trametinib is the first regimen demonstrated to have potent clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and is well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.19",CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1,"Dabrafenib is a competitive and selective BRAF inhibitor by binding to its ATP pocket.,Although dabrafenib can inhibit wild-type BRAF, it has a higher affinity for mutant forms of BRAF, including BRAF VE, BRAF VK, and BRAF VD.BRAF is a serine/threonine protein kinase and is involved in activating the RAS/RAF/MEK/ERK or MAPK pathway, a pathway that is implicated in cell cycle progression, cell proliferation, and arresting apoptosis.,,,Therefore, constitutive active mutation of BRAF such as BRAF VE is frequently observed in many types of cancer, including melanoma, lung cancer, and colon cancer.TargetActionsOrganismASerine/threonine-protein kinase B-rafinhibitorHumansARAF proto-oncogene serine/threonine-protein kinaseinhibitorHumansUSerine/threonine-protein kinase SIKinhibitorHumansUSerine/threonine-protein kinase NekinhibitorHumansULIM domain kinase inhibitorHumans",[],"['Amines', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'B-Raf serine-threonine kinase (BRAF) inhibitors', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inducers (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Enzyme Inhibitors', 'Hydroxylamines', 'Hyperglycemia-Associated Agents', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B1/SLCO1B1 Substrates', 'OATP1B3 inhibitors', 'OATP1B3 substrates', 'OCT2 Inhibitors', 'Organic Anion Transporter 1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B1 Inhibitors', 'Organic Anion Transporting Polypeptide 1B3 Inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Photosensitizing Agents', 'Potential QTc-Prolonging Agents', 'Protein Kinase Inhibitors', 'Proto-Oncogene Proteins B-raf, antagonists & inhibitors', 'QTc Prolonging Agents', 'UGT1A1 Inhibitors']" +DB01051,Novobiocin,"Novobiocin is an antibiotic compound derived fromStreptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)","['P0A0K8', 'Q06AK7']","Novobiocin is an aminocoumarin antibiotic that was produced by the actinomyceteStreptomyces niveus. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. Other antibiotics in the aminocoumarin class include coumermycin A1 and clorobiocin.",CO[C@@H]1[C@@H](OC(N)=O)[C@@H](O)[C@H](OC2=C(C)C3=C(C=C2)C(O)=C(NC(=O)C2=CC=C(O)C(CC=C(C)C)=C2)C(=O)O3)OC1(C)C,"Novobiocin is an aminocoumarinthat works by inhibiting the GyrB subunit of the bacterial DNA gyrase enzyme involved in energy tranduction. Similar to other aminocoumarin antibiotics, it acts as a competitive inhibitor of the ATPase reaction catalysed by GyrB.TargetActionsOrganismADNA gyrase subunit BinhibitorStaphylococcus aureusUDNA topoisomerase inhibitorStaphylococcus aureus",[],"['Aminocoumarins', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'BCRP/ABCG2 Inhibitors', 'Benzopyrans', 'Carbohydrates', 'Coumarins', 'Enzyme Inhibitors', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring', 'Nucleic Acid Synthesis Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'Organic Anion Transporting Polypeptide 2B1 Inhibitors', 'Pyrans']" +DB01034,Cerulenin,"Cerulenin is an antifungal agent whose activity interferes with or otherwise acts to prevent the formation of fatty acids and sterols. In fatty acid synthesis, reported to bind in equimolar ratio to b-keto-acyl-ACP synthase. In sterol synthesis, inhibits HMG-CoA synthetase activity. It is also shown to inhibit feeding and induce dramatic weight loss in mice. It is found naturally in the Cephalosporium caerulensfungus.","['P0A953', 'P0AAI5', 'P0A6R0', 'P49327']","Cerulenin is an antifungal antibiotic isolated fromCephalosporium caerulens. It interrupts fungal growth by inhibiting the biosynthesis of sterols and fatty acids (inhibits bacterial fatty acid synthesis). It also inhibits HMG-CoA synthetase activity. Cerulenin produces metabolic effects similar to effects of leptin, but through mechanisms that are independent of, or down-stream from, both leptin and melanocortin receptors.",[H][C@]1(O[C@]1([H])C(=O)CC\C=C\C\C=C\C)C(N)=O,"Irreversibly binds to fatty acid synthase, specifically b-ketoacyl-acyl carrier protein synthase (FabH, FabB and FabF condensation enzymes). A number of tumor cells and cell lines have been observed to have highly upregulated expression and activity of fatty acid synthase (FAS). Inhibition of FAS by cerulenin leads to cytotoxicity and apoptosis in human cancer cell lines, an effect believed to be mediated by the accumulation of malonyl-coenzyme A in cells with an upregulated FAS pathway.TargetActionsOrganismA-oxoacyl-[acyl-carrier-protein] synthase inhibitorEscherichia coli (strain K)A-oxoacyl-[acyl-carrier-protein] synthase inhibitorEscherichia coli (strain K)A-oxoacyl-[acyl-carrier-protein] synthase inhibitorEscherichia coli (strain K)AFatty acid synthaseinhibitorHumans",[],"['Amides', 'Anti-Infective Agents', 'Antifungal Agents', 'Fatty Acid Synthesis Inhibitors', 'Hypolipidemic Agents', 'Lipid Regulating Agents']" +DB08911,Trametinib,"Trametinibis a kinase inhibitor used alone or in combination with dabrafenib to treat patients with cancers with specific BRAF mutations, such as melanoma and non-small cell lung cancer.","['Q02750', 'P36507']","Trametinib inhibits cell growth of various BRAF V600 mutation-positive tumoursin vitroandin vivo. Trametinib is often used in combination with dabrafenib, a BRAF inhibitor. In BRAF-mutant colorectal cancer, induction of EGFR-mediated MAPK pathway re-activation has been identified as a mechanism of intrinsic resistance to BRAF inhibitors.7",CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1,"The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway, also known as the RAS-RAF-MEK-ERK pathway, activates a cascade of cell surface receptors and intracellular downstream signalling molecules. Activated RAS protein activates RAF, a serine/threonine kinase that activates other downstream proteins,such as mitogen-activated extracellular signal-regulated kinase (MEK) and MEK. MEKs then activates ERK, which works on several target proteins and nuclear transcription factors that regulate cell proliferation, differentiation, survival, and growth.,ARAF, BRAF, and CRAF are three isoforms of RAF identified in humans. In particular, BRAF is known to be the most critical activator in melanoma.,Certain cancers, such as melanoma, are associated with BRAF mutations, with one study suggesting that BRAF is mutated in about % of melanoma tumours.BRAF VE and VK mutations account for % of BRAF mutations.These BRAF mutations cause constitutive activation of the RAS-RAF-MEK-ERK pathway,,leading to dysregulated proliferation and survival of tumour cells.Trametinib is a reversible, highly selective, allosteric inhibitor of MEK and MEK.,By binding to unphosphorylated MEK and MEK with high affinity, trametinib blocks the catalytic activity of MEKs.,,It also maintains MEK in an unphosphorylated form, preventing phosphorylation and activation of MEKs.,,In vitrostudies suggest that dual inhibition of the MAPK pathway by MEK and B-RAF inhibitors is associated with a synergistic effect and improved therapeutic efficacy in cancers compared to using either drug alone.The combined use of trametinib and dabrafenib, a BRAF inhibitor, results in more significant growth inhibition of BRAF V mutation-positive tumour cell linesin vitroand prolonged inhibition of tumour growth in BRAF V mutation-positive tumour xenografts compared to either drug alone.The combined inhibition of MEK by trametinib and RAF by dabrafenib delays the emergence of resistancein vivoin BRAF V mutation-positive melanoma xenografts.TargetActionsOrganismADual specificity mitogen-activated protein kinase kinase inhibitorHumansADual specificity mitogen-activated protein kinase kinase inhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Kinase Inhibitor', 'MAP Kinase Kinase 1, antagonists & inhibitors', 'MAP Kinase Kinase 2, antagonists & inhibitors', 'Mitogen-activated protein kinase (MEK) inhibitors', 'Narrow Therapeutic Index Drugs', 'Protein Kinase Inhibitors', 'Pyridines', 'Pyrimidines']" +DB01892,Hyperforin,"Hyperforin is a phytochemical generated by the plants of the Hypericum family. One of the most important members of this family, due to its medical properties, isHypericum perforatum, also known as St John's wort.","['O75469', 'P23219', 'P09917']","Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort. It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 mcg/ml for all compounds, with the exception of glutamate, which is in the 0.5 mcg/ml range. It appears to exert these effects by activating the transient receptor potential ion channel TRPC6. Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake. Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).",CC(C)C(=O)[C@@]12C(O)=C(CC=C(C)C)C(=O)[C@@](CC=C(C)C)(C[C@H](CC=C(C)C)[C@@]1(C)CCC=C(C)C)C2=O,"Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort. It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC values of .-. mcg/ml for all compounds, with the exception of glutamate, which is in the . mcg/ml range. It appears to exert these effects by activating the transient receptor potential ion channel TRPC. Activation of TRPC induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake.TargetActionsOrganismUNuclear receptor subfamily group I member Not AvailableHumansUProstaglandin G/H synthase inhibitorHumansUArachidonate -lipoxygenaseinhibitorHumans",[],"['Benzene Derivatives', 'OATP1B1/SLCO1B1 Inhibitors', 'Phenols']" +DB04869,Olcegepant,"Boehringer Ingelheim Pharmaceuticals’ olcegepant (BIBN 4096) is a selective Calcitonin Gene-Related Peptide (CGRP) antagonist, a new class of drugs in development for the treatment of acute migraine attacks. Olcegepant is undergoing phase II trials in Europe and the US, with preliminary results suggesting that CGRP antagonists may represent a potential new approach to the treatment of migraine.","['Q16602', 'P06881']","Olcegepant is a calcitonin gene-related peptide (CGRP) antagonist. In preclinical studies, olcegepant attenuated arterial dilation induced by CGRP or electrical stimulation. In a phase II clinical trial, olcegepant reduced the severity of headache in 60% of migraine sufferers and met secondary endpoints including headache-free rate and rate of sustained response. Only mild-to-moderate transient adverse events were observed, with no adverse cardiovascular symptoms reported. The compound appears to be an effective anti-migraine medication that is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans and dihydroergotamine in certain patients.",NCCCC[C@H](NC(=O)[C@@H](CC1=CC(Br)=C(O)C(Br)=C1)NC(=O)N1CCC(CC1)N1CC2=C(NC1=O)C=CC=C2)C(=O)N1CCN(CC1)C1=CC=NC=C1,"Migraine involves dysfunction of brainstem pathways that normally modulate sensory input. The involvement of calcitonin gene-related peptide (CGRP) in migraine pathology is supported by both clinical and experimental evidence. The release of CGRP and other neuropeptides from trigeminal nerves is thought to mediate neurogeate inflammation within the meninges which contributes to the generation of severe cerebral pain experienced during migraine attack. CGRP antagonists such as olcegepant bind at CGRP receptors, blocking the effect CGRP and thus reducing inflammation.TargetActionsOrganismUCalcitonin gene-related peptide type receptorantagonistHumansUCalcitonin gene-related peptide Not AvailableHumans",[],"['Amino Acids, Peptides, and Proteins', 'Analgesics', 'Calcitonin Gene-Related Peptide Receptor Antagonists', 'Central Nervous System Agents', 'Heterocyclic Compounds, Fused-Ring', 'Oligopeptides', 'Peptides', 'Peripheral Nervous System Agents', 'Receptors, Calcitonin Gene-Related Peptide, antagonists & inhibitors', 'Sensory System Agents']" +DB00998,Frovatriptan,Frovatriptanis a 5-HT1B/1D receptor agonist used to treat migraines.,"['P28221', 'P28222']","Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT1Band 5-HT1Dreceptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT1B/1Dreceptor agonists. Frovatriptan has no significant effects on GABAAmediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Research has shown that migraine can be caused by the swelling of blood vessels around the brain. Frovatriptan eases the pain associated with migraine by narrowing these blood vessels. Frovatriptan has one of the highest affinities for the 5-HT1Bof the second-generation triptan agonists.",CN[C@@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=O,"Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: () stimulation of presynaptic -HTDreceptors, which serves to inhibit both dural vasodilation and inflammation; () direct inhibition of trigeminal nuclei cell excitability via -HTB/Dreceptor agonism in the brainstem and () vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular -HTBreceptor agonism.TargetActionsOrganismA-hydroxytryptamine receptor DagonistHumansA-hydroxytryptamine receptor BagonistHumans",[],"['Agents that produce hypertension', 'Amines', 'Analgesics', 'Antidepressive Agents', 'Antimigraine Preparations', 'Biogenic Amines', 'Biogenic Monoamines', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Migraine Disorders', 'Nervous System', 'Neurotransmitter Agents', 'Selective Serotonin 5-HT1 Receptor Agonists', 'Selective Serotonin Agonists', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 1b Receptor Agonists', 'Serotonin 1d Receptor Agonists', 'Serotonin 5-HT1 Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists', 'Serotonin-1b and Serotonin-1d Receptor Agonist', 'Triptans']" +DB00050,Cetrorelix,Cetrorelixis a synthetic peptide antagonist of gonadotropin releasing hormone used to prevent luteinizing hormone surges in women undergoing assisted reproduction therapy.,"['P30968', 'P22888']","Cetrorelix is a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity. GnRH induces the production and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the gonadotrophic cells of the anterior pituitary. Due to a positive estradiol (E2) feedback at midcycle, GnRH liberation is enhanced resulting in an LH-surge. This LH-surge induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization as indicated by rising progesterone levels. Cetrorelix competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner.",CC(C)C[C@H](NC(=O)[C@@H](CCCNC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC1=CN=CC=C1)NC(=O)[C@@H](CC1=CC=C(Cl)C=C1)NC(=O)[C@@H](CC1=CC2=CC=CC=C2C=C1)NC(C)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O,Cetrorelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion. It competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner.TargetActionsOrganismAGonadotropin-releasing hormone receptorantagonistHumansULutropin-choriogonadotropic hormone receptorNot AvailableHumans,['Controlled Ovarian Stimulation'],"['Amino Acids, Peptides, and Proteins', 'Anti-Gonadotropin-Releasing Hormones', 'Decreased GnRH Secretion', 'Fertility Agents', 'Fertility Agents, Female', 'Gonadotropin Releasing Hormone Receptor Antagonists', 'Gonadotropin-releasing Hormone Antagonists', 'Hormone Antagonists', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypothalamic Hormones', 'Nerve Tissue Proteins', 'Neuropeptides', 'Oligopeptides', 'Peptide Hormones', 'Peptides', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormone-Releasing Hormones', 'Proteins', 'Reproductive Control Agents', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB08880,Teriflunomide,Teriflunomideis a pyrimidine synthesis inhibitor with anti-inflammatory and immunomodulatory properties used to treat patients with the relapsing-remitting form of multiple sclerosis.,['Q02127'],"Teriflunomide is an immunomodulatory agent that decreases the amount of activated CNS lymphocytes, which results in anti-inflammatory and antiproliferative effects.",C\C(O)=C(/C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F,"The exact mechanism by which teriflunomide acts in MS is not known. What is known is that teriflunomide prevents pyrimidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase, and this may be involved in its immunomodulatory effect in MS.TargetActionsOrganismUDihydroorotate dehydrogenase (quinone), mitochondrialinhibitorHumans",[],"['Acids, Acyclic', 'Amines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Aniline Compounds', 'Anti-Inflammatory Agents', 'Antineoplastic and Immunomodulating Agents', 'Antirheumatic Agents', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'Butyrates', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inducers (weak)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Dihydroorotate Dehydrogenase Inhibitors', 'Fatty Acids', 'Fatty Acids, Volatile', 'Hepatotoxic Agents', 'Hydroxy Acids', 'Immunologic Factors', 'Immunomodulatory Agents', 'Immunosuppressive Agents', 'Lipids', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'Peripheral Nervous System Agents', 'Pyrimidine Synthesis Inhibitor', 'Selective Immunosuppressants', 'Sensory System Agents']" +DB08837,Tetraethylammonium,"Tetraethylammonium is an experimental drug with no approved indication or marketed formulation. The only marketed drug containing tetraethylammonium was a combination drug called Fosglutamina B6, but this drug has now been discontinued. As an experimental agent, tetraethylammonium is used in its salt forms such as tetraethylammonium chloride and tetraethylammonium bromide. Its mechanism of action is still being investigated, but it is known that tetraethylammonium blocks autonomic ganglia, calcium- and voltage- activated potassium channels, and nicotinic acetylcholine receptors. Because of its inhibitory actions at the autonomic ganglia, tetraethylammonium was thought to be a potential therapeutic vasodilator but serious toxic effects were found. The most common use of tetraethylammonium presently is as a pharmacological research agent that blocks selective potassium channels. Structurally, tetraethylammonium is positively charged due to its central quaternary ammonium.","['P0A334', 'Q9UGM1', 'Q08460', 'Q09470']",Tetraethylammonium is a vasodilator because it blocks autonomic ganglia and prevents signals carrying vasoconstrictor impulses from proceeding.,CC[N+](CC)(CC)CC,"Tetraethylammonium's mechanism of action is still being investigated, but it is known that it blocks autonomic ganglia, calcium- and voltage- activated potassium channels, and nicotinic acetylcholine receptors.TargetActionsOrganismUpH-gated potassium channel KcsAinhibitorStreptomyces lividansUNeuronal acetylcholine receptor subunit alpha-agonistinhibitorHumansUCalcium-activated potassium channel subunit alpha-inhibitorMouseUPotassium voltage-gated channel subfamily A member blockerHumans",[],"['Amines', 'Cardiovascular Agents', 'Ganglion Blockers', 'MATE 1 Substrates', 'MATE 2 Substrates', 'MATE substrates', 'Membrane Transport Modulators', 'OCT2 Substrates', 'Onium Compounds', 'Potassium Channel Blockers', 'Quaternary Ammonium Compounds', 'Tetraethylammonium Compounds']" +DB00504,Levallorphan,"An opioid antagonist with properties similar to those of naloxone; in addition it also possesses some agonist properties. It should be used cautiously; levallorphan reverses severe opioid-induced respiratory depression but may exacerbate respiratory depression such as that induced by alcohol or other non-opioid central depressants. (From Martindale, The Extra Pharmacopoeia, 30th ed, p683)",['P35372'],"Levallorphan, an opioid antagonist similar to naloxone, is used to treat drug overdoses. Levallorphan differs from naloxone in that it also possesses some agonist properties. It is an analogue of levelorphanol that counteracts the actions of narcotic analgesics such as morphine. It is used especially in the treatment of respiratory depression due to narcotic overdoses. Levallorphan prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.",[H][C@@]12CCCC[C@@]11CCN(CC=C)[C@@H]2CC2=C1C=C(O)C=C2,Levallorphan antagonizes opioid effects by competing for the same receptor sites. It binds to the opioid mu receptor and the nicotinic acetylcholine receptor alpha/alpha.TargetActionsOrganismAMu-type opioid receptorpartial agonistHumans,[],"['Alkaloids', 'Central Nervous System Agents', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Opiate Alkaloids', 'Opioid Antagonists', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Sensory System Agents']" +DB00416,Metocurine iodide,Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. It is used as an anesthesia adjunct to induce skeletal muscle relaxation and to reduce the intensity of muscle contractions in convulsive therapy Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. Metocurine Iodide is no longer available on the US market.,['Q15822'],"Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of metocurine iodide. Repeated administration of maintenance doses of metocurine iodide has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results.",[I-].[I-].[H][C@@]12CC3=CC=C(OC4=C5C(CC[N+](C)(C)[C@]5([H])CC5=CC(OC6=C(OC)C=C(CC[N+]1(C)C)C2=C6)=C(OC)C=C5)=CC(OC)=C4OC)C=C3,"Metocurine iodide antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumans",[],"['Alkaloids', 'Amines', 'Anticholinergic Agents', 'Benzylisoquinolines', 'Central Nervous System Depressants', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Nicotinic Antagonists', 'Onium Compounds', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds', 'Tetrahydroisoquinolines']" +DB06595,Midostaurin,"Midostaurinis an antineoplastic agent used to treat high-risk acute myeloid leukemia (AML) with specific mutations, aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM-AHN), or mast cell leukemia (MCL).","['P17252', 'P35968', 'P16234', 'P09619', 'P36888', 'P10721']","It targets multiple WT and mutated kinases that, when activated, constitutively stimulate aberrant signalling cascades that lead to malignancies such as AML and ASM. Alternative pharmacodynamic effect of midostaurin in prolonging QTc intervals was not clinically significant in patients with advanced SM or AML when compared to placebo. Midostaurin is therapeutically beneficial as a combination therapy for patients undergoing chemotherapy.",CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C(C=CC=C4)N21)C1=C3CNC1=O)N(C)C(=O)C1=CC=CC=C1,"It potently inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites CGP and CGP inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR, KIT, PDGFR and WT and/or mutant FLT tyrosine kinases. Inhibition of FLT receptor signalling cascades induces apoptosis of target leukemia cells expressing target receptors and mast cells, in addition to its antiproliferative activity toward multiple cancer cell lines. +Midostaurin also interacts with organic anion transporter (OATP) A and multidrug resistance protein (MRP)- according to preliminary in vitro studies.TargetActionsOrganismAProtein kinase C alpha typeantagonistinhibitorHumansAVascular endothelial growth factor receptor antagonistinhibitorHumansAPlatelet-derived growth factor receptor alphaantagonistinhibitorHumansAPlatelet-derived growth factor receptor betaantagonistinhibitorHumansAReceptor-type tyrosine-protein kinase FLTantagonistinhibitorHumansUMast/stem cell growth factor receptor KitantagonistinhibitorHumans",[],"['Alkaloids', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbazoles', 'Cytochrome P-450 CYP1A2 Inducers', 'Cytochrome P-450 CYP1A2 Inducers (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strong)', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (strong)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A7 Inducers', 'Cytochrome P-450 CYP3A7 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Indole Alkaloids', 'Indoles', 'Indolizidines', 'Indolizines', 'Kinase Inhibitor', 'Narrow Therapeutic Index Drugs', 'Protein Kinase C, antagonists & inhibitors', 'Protein Kinase Inhibitors', 'Receptor Tyrosine Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB00385,Valrubicin,Valrubicinis an anthracycline used intravesically in the treatment of BCG-resistant bladder carcinoma.,['P11388'],Valrubicin is an anticancer agent.,[H][C@@]1(C[C@@](O)(CC2=C(O)C3=C(C(O)=C12)C(=O)C1=C(OC)C=CC=C1C3=O)C(=O)COC(=O)CCCC)O[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1,"Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where after DNA intercalation, it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II.TargetActionsOrganismADNAintercalationHumansADNA topoisomerase -alphainhibitorHumans",[],"['Anthracycline Topoisomerase Inhibitor', 'Anthracyclines', 'Anthracyclines and Related Substances', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Carbohydrates', 'Cytotoxic Antibiotics and Related Substances', 'Enzyme Inhibitors', 'Glycosides', 'Naphthacenes', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB01319,Fosamprenavir,Fosamprenaviris an antiretroviral agent used for the treatment and postexposure prophylaxis of human immunodeficiency virus (HIV-1) infection.,['Q72874'],"Fosamprenavir is hydrolyzed by cellular phosphatases to the antiretroviral protease inhibitor amprenavir. This hydrolysis allows for the slow release of amprenavir, reducing the number of pills a patient must take.",CC(C)CN(C[C@@H](OP(O)(O)=O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1,"Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV- protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV- protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Acids, Acyclic', 'Amides', 'Amprenavir and Prodrugs', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'Protease Inhibitors', 'Sulfones', 'Sulfur Compounds', 'Viral Protease Inhibitors']" +DB00219,Oxyphenonium,"A quaternary ammonium anticholinergic agent with peripheral side effects similar to those of atropine. It is used as an adjunct in the treatment of gastric and duodenal ulcer, and to relieve visceral spasms. The drug has also been used in the form of eye drops for mydriatic effect. [PubChem]",['P11229'],"Oxyphenonium is an anticholinergic drug, a medication that reduces the effect of acetylcholine, a chemical released from nerves that stimulates muscles, by blocking the receptors for acetylcholine on smooth muscle (a type of muscle). It also has a direct relaxing effect on smooth muscle. Oxyphenonium is used to treat or prevent spasm in the muscles of the gastrointestinal tract in the irritable bowel syndrome. In addition, Oxyphenonium inhibits gastrointestinal propulsive motility and decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretions.",CC[N+](C)(CC)CCOC(=O)C(O)(C1CCCCC1)C1=CC=CC=C1,Action is achieved via a dual mechanism: () a specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor sites and () a direct effect upon smooth muscle (musculotropic).TargetActionsOrganismAMuscarinic acetylcholine receptor MantagonistHumans,[],"['Agents producing tachycardia', 'Alimentary Tract and Metabolism', 'Amines', 'Anticholinergic Agents', 'Autonomic Agents', 'Cholinergic Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Muscarinic Antagonists', 'Mydriatics', 'Neurotransmitter Agents', 'Onium Compounds', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds', 'Synthetic Anticholinergics, Quaternary Ammonium Compounds']" +DB00377,Palonosetron,"Palonosetronis a serotonin antagonist used in the prophylaxis or management of vomiting that results from emetogenic chemotherapy, and for the management of postoperative nausea and vomiting.",['P46098'],"Palonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT3receptor antagonist that is pharmacologically related to other 5-HT3receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT3receptors, but has little to no affinity for other receptors. The serontonin 5-HT3receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.",[H][C@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]1CN2CCC1CC2,"Palonosetron is a selective serotonin -HTreceptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of -HTreceptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of -HTreceptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between between serotonin and emesis beyond the first day after a dose have not been established, and -HTreceptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron's potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.TargetActionsOrganismA-hydroxytryptamine receptor AantagonistHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'Antiemetic Serotonin 5-HT3 Receptor Antagonists', 'Antiemetics', 'Antiemetics and Antinauseants', 'Autonomic Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Neurotransmitter Agents', 'Peripheral Nervous System Agents', 'Quinuclidines', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 3 Receptor Antagonists', 'Serotonin 5-HT3 Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB14881,Oliceridine,"Oliceridineis a biased opioid agonist indicated for the management of severe acute pain in adult patients. Through preferential activation of G-protein-coupled signalling pathways, oliceridine provides analgesic effect with a comparable or improved safety profile over conventional opioid agonists.",['P35372'],"Oliceridine is a biased μ-opioid receptor agonist that acts through downstream signalling pathways to exert antinociceptive analgesia in patients experience severe acute pain.1,2,3,4,5,15Results from multiple clinical studies6,7,8,9,10,15and simulation data11,12demonstrate that oliceridine exerts significant analgesic benefits within 5-20 minutes following administration but dissipates quickly with a half-life between one and three hours.6,7,8,9,10,15Despite an improved adverse effect profile over conventional opioids6,7,8,9,10,15, oliceridine carries important clinical warnings. Oliceridine has the potential to cause severe respiratory depression, especially in patients who are elderly, cachectic, debilitated, or who otherwise have chronically impaired pulmonary function. In addition, severe respiratory depression or sedation may occur in patients with increased intracranial pressure, head injury, brain tumour, or impaired consciousness. Patients with adrenal insufficiency or severe hypotension may require treatment alterations or discontinuation. Finally, oliceridine has been demonstrated to prolong the QTc interval and has not been properly evaluated beyond a maximum daily dose of 27 mg; it is recommended not to exceed 27 mg per day.15",COC1=C(CNCC[C@]2(CCOC3(CCCC3)C2)C2=NC=CC=C2)SC=C1,"Pain perception follows a complex pathway initiated in primary sensory neurons, subsequently transmitted to the spinal cord dorsal horn and through ascending axons to multiple regions within the thalamus, brainstem, and midbrain, and finally relayed through descending signals that either inhibit or facilitate the nociceptive signalling.,Opioid receptors are seven-transmembrane G-protein-coupled receptors (GPCRs) that can be divided into μ, κ, δ, and opioid-like- (ORL) subtypes,,. However, the μ-opioid receptor is predominantly targeted by and is responsible for the effects of traditional opioids.GPCRs in the inactive state are bound intracellularly by a complex consisting of a Gα, β, and γ subunit together with guanosine diphosphate (GDP). Activation of the GPCR through extracellular agonist binding catalyzes the replacement of GDP with guanosine triphosphate (GTP), dissociation of both Gα-GTP and a βγ heterodimer, and subsequent downstream effects.In the case of the μ-opioid receptor, the Gα-GTP directly interacts with the potassium channel Kir while the dissociated Gβγ subunit directly binds to and occludes the pore of P/Q-, N-, and L-type Ca+channels. Furthermore, opioid receptor activation inhibits adenylyl cyclase, which in turn reduces cAMP-dependent Ca+influx. By altering membrane ion conductivity, these effects modulate nociceptive signalling and produce an analgesic effect.,,In addition to the G-protein pathway, μ-opioid receptor activation can also result in downstream signalling through β-arrestin, which results in receptor internalization and is associated with negative effects of opioid use including respiratory depression, gastrointestinal effects, and desensitization/tolerance.,,,,Oliceridine acts as a ""biased agonist"" at the μ-opioid receptor by preferentially activating the G-protein pathway with minimal receptor phosphorylation and recruitment of β-arrestin.,Competetive binding assays and structural modelling suggest that the binding site for oliceridine on the μ-opioid receptor is the same as for classical opioids.,However, molecular modelling supports a model whereby oliceridine binding induces a different intracellular conformation of the μ-opioid receptor, specifically due to a lack of coupling with transmembrane helix six, which confers the specificity for G-protein over β-arrestin interaction.Numerousin vitro,in vivo, and clinical studies support the view that this biased agonism results in comparable analgesia compared with traditional opioids at a comparable or decreased risk of opioid-related adverse effects such as constipation and respiratory depression.,,,,,,,TargetActionsOrganismAMu-type opioid receptoragonistHumans",[],"['Analgesics', 'Anesthetics', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Ligands', 'Narcotics', 'Nervous System', 'Neuraxial Anesthetics', 'Opiate Agonists', 'Opioid Agonist', 'Opioids', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Sulfur Compounds']" +DB04849,Cediranib,The novel indole-ether quinazoline Cediranib is a highly potent (IC50< 1 nmol/L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro. It is being developed clinically as a once-daily oral therapy for the treatment of cancer.,['P35968'],"Cediranib is a once-daily, orally available, highly potent and selective VEGF signalling inhibitor that inhibits all three VEGF receptors. The preclinical profile of Cediranib indicates that it has the potential to be the 'best in class' VEGF signalling inhibitor. Phase I data indicate that Cediranib is generally well tolerated, with the most common dose related adverse events being diarrhoea, hoarseness, headache and hypertension.",COC1=CC2=C(C=C1OCCCN1CCCC1)N=CN=C2OC1=C(F)C2=C(NC(C)=C2)C=C1,"Cediranib inhibits vacular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK). By forming a blockade at the VEGF receptors, Cediranib limits the growth of new blood vessels, which are essential to supporting tumor growth. Thus, lacking sufficient blood supply, tumor cells become starved for nutrients, slowing or halting growth and potentially improving the efficacy of other treatments. Preclinical evidence indicated that the drug had a high affinity at these sites, and was well tolerated and efficacious in animal studies.TargetActionsOrganismUVascular endothelial growth factor receptor Not AvailableHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Protein Kinase Inhibitors', 'Tyrosine Kinase Inhibitors', 'Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors']" +DB00432,Trifluridine,"Trifluridineis a nucleoside metabolic inhibitor used to treat keratoconjunctivitis and epithelial keratitis caused by simplex virus, and as a part of chemotherapy for certain types of metastatic gastrointestinal cancers.",['P04818'],"Trifluridine exhibits an antiviral effect against herpes simplex virus, types 1 and 2 and vacciniavirus both in vitro and in vivo1. Some strains of adenovirus that contribute to the pathology of keratoconjunctivitis were shown to be susceptible to trifluridinein vitro1. While there is evidence from a study that cross-resistance may develop between trifluridine andidoxuridineorvidarabine, trifluridine was shown to effective in treating dendritic ulcers in patients with herpetic keratitis who are unresponsive toidoxuridineorvidarabinebased on the results from masked comparative trials1. In nonclinical studies, trifluridine/tipiracil hydrochloride demonstrated antitumour activity against both 5-fluorouracil (5-FU) sensitive and resistant colorectal cancer cell lines10. The cytotoxic activity of trifluridine and tipiracil against several human tumour xenografts show high correlation with the amount of trifluridine incorporated into DNA, indicating that the primary mechanism of action of trifluridine involves the direct incorporation into the cancer cell DNA10. Trifluridine and tipiracil demonstrated anti-tumor activity against KRAS wild-type and mutant human colorectal cancer xenografts in miceLabel.In clinical studies comprised of patients with previously treated metastatic colorectal cancer, treatment of trifluridine in combination with tipiracil in addition to best supportive care over a 5- or 7-month period resulted in increased progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) compared to placebo10. In an open-label study, administration of trifluridine at the recommended dosage in patients with advanced solid tumors had no clinically relevant effect on QT/QTc prolongation compared with placeboLabel. Two out of 48 patients displayed had QTc greater than 500 msec and 1 of 42 patients (2.4%) had a QTc increase from baseline greater than 60 msecLabel.",OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(C(=O)NC1=O)C(F)(F)F,"The mechanism of action of trifluridine as an antiviral agent has not been fully elucidated, but appears to involve the inhibition of viral replication. Trifluridine gets incorporated into viral DNA during replication, which leads to the formation of defective proteins and an increased mutation rate. Trifluridine also mediates antineoplastic activities via this mechanism; following uptake into cancer cells, trifluridine is rapidly phosphorylated by thymidine kinase to its active monophosphate form. Subsequent phosphorylation produces trifluridine triphosphate, which is readily incorporated into the DNA of tumour cells in place of thymidine bases to perturb DNA function, DNA synthesis, and tumour cell proliferationLabel. As trifluridine is subject to rapid degradation by TPase and readily metabolised by a first-pass effect following oral administration, tipiracil is added in the antineoplastic combination product as an inhibitor of TPase to increase the bioavailability of trifluridine. Trifluridine monophosphate also reversibly inhibits thymidylate synthetase (TS), an enzyme that is necessary for DNA synthesis and which levels are shown to be elevated different cancer cell lines. Up-regulation of the expression of the TS enzyme may also lead to the resistance to antineoplastic therapies, such as -fluorouracil (-FU). [A However, this inhibitory effect is not considered to be sufficient enough to fully contribute to the cytotoxicity in cancer cells.TargetActionsOrganismADNAother/unknownHumansAThymidylate synthaseinhibitorHumans",[],"['Anti-Infective Agents', 'Antimetabolites', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Antiviral Agents', 'Deoxyribonucleosides', 'Drugs that are Mainly Renally Excreted', 'Immunosuppressive Agents', 'Noxae', 'Nucleic Acid Synthesis Inhibitors', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleoside Analog Antiviral', 'Nucleoside Metabolic Inhibitor', 'Nucleosides', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Substrates', 'Ophthalmologicals', 'Pyrimidine Analogues', 'Pyrimidine Nucleosides', 'Pyrimidines', 'Sensory Organs', 'Toxic Actions']" +DB09288,Propacetamol,"Propacetamol is a non-opioid analgesic devoid of the major contraindications.1It is a derivative ofacetaminophen, or paracetamol, with the molecular formula glycine, N, N-diethyl-,4-(acetylamino)phenyl ester. Propacetamol is a parenteral formulation of paracetamol and thus, it is a prodrug that is completely hydrolyzed to paracetamol.3It is not available in the United States but this prodrug has been widely used in other countries such as France since 1985.5","['P23219', 'P35354', 'Q8NER1', 'P21554']","Propacetamol is hydrolyzed to paracetamol and then it presents a weak inhibition of COX-1 and COX-2 which is translated into a low anti-inflammatory activity. Therefore, in high inflammatory conditions, such as rheumatoid arthritis, these agents show limited in vivo suppression of inflammation and platelet activity. The formation of N-arachidonoylphenolamine, donates paracetamol with analgesic and antipyretic properties.8",CCN(CC)CC(=O)OC1=CC=C(NC(C)=O)C=C1,"As propacetamol is a prodrug, its mechanism of action is directly linked to the activity of paracetamol. The mechanism of action of paracetamol is described by the inhibition of prostaglandin synthesis.This inhibition is attained by inhibition of COX- and COX- in an environment where arachidonic acid and peroxides are kept low.It is considered that paracetamol presents a very complex mechanism of action involving effects in the peripheral system, described by direct COX inhibition; the central system, characterized by inhibition of COX, serotonergic descending neuronal pathway, L-arginine/NO pathway and cannabinoid system; and a redox mechanism.In the brain and spinal cord, paracetamol can combine with arachidonic acid to form N-arachidonoylphenolamine. This metabolite is an activator of capsaicin receptor (TRPV) and cannabinoid CB.TargetActionsOrganismAProstaglandin G/H synthase antagonistHumansAProstaglandin G/H synthase antagonistHumansATransient receptor potential cation channel subfamily V member antagonistHumansACannabinoid receptor antagonistHumans",[],"['Acetaminophen and Prodrugs', 'Acetanilides', 'Agents causing hyperkalemia', 'Agents that produce hypertension', 'Amides', 'Amines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anilides', 'Aniline Compounds', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Antirheumatic Agents', 'Central Nervous System Agents', 'Cholinesterase substrates', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Nephrotoxic agents', 'Nervous System', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Prodrugs', 'Sensory System Agents', 'UGT1A1 Substrates', 'UGT1A6 substrate', 'UGT1A9 Substrates']" +DB11638,Artenimol,Artenimol is an artemisinin derivative and antimalarial agent used in the treatment of uncomplicatedPlasmodium falciparuminfectionsLabel. It was first authorized for market by the European Medicines Agency in October 2011 in combination withPiperaquineas the product Eurartesim. Artemisinin combination therapy is highly effective against malaria and stongly recommended by the World Health Organization12.,"['P63261', 'P49419', 'P07355', 'P25705', 'O75964', 'P48047', 'P20810', 'P49368', 'P23528', 'O00299', 'P21291', 'Q16555', 'P15924', 'P68104', 'P06733', 'P21333', 'Q9C0B1', 'P11413', 'O14556', 'P06744', 'P22626', 'Q14103', 'P61978', 'Q5SSJ5', 'P04792', 'P46940', 'Q92945', 'P00338', 'P07195', 'P09382', 'P27816', 'P40925', 'P55786', 'P07737', 'P00558', 'P14618', 'P62937', 'Q06830', 'P27635', 'P50914', 'Q07020', 'P62750', 'P42766', 'P36578', 'P62277', 'P08708', 'P62269', 'P39019', 'P62857', 'P46782', 'P62753', 'P62241', 'P46781', 'Q15637', 'P23246', 'P62316', 'P37108', 'Q08170', 'Q01995', 'P37802', 'P60174', 'P09493', 'Q71U36', 'P08670', 'Q15942', 'P11142', 'Q9BUF5', 'P04350', 'P07437', 'P04075', 'P04406', 'P99999', 'P18669', 'P35579', 'P07237', 'P17844', 'P34897', 'Q13838', 'P06748', 'Q8I3Z5', 'Q5R2K6', 'Q6LFH8', 'Q00080', 'P13568', 'Q8IKW5', 'P86287', 'Q8IKK7', 'P14223', 'C6KT34', 'Q8IC05', 'Q8IKF0', 'C6KTA4', 'Q27743', 'C0H4Y6', 'Q8IDH5', 'Q8II73', 'Q8I2Z8', 'Q8ILF7', 'Q8I0V4', 'P20035', 'Q8IJN7', 'Q8IKH8', 'A0A143ZZK9', 'P14642', 'P13817', 'Q7K6A4', 'Q8IKR1', 'Q8I431', 'Q8IDQ9', 'O97313', 'Q8IJT2', 'Q8IJC6', 'C0H571', 'T1RTG8', 'C0H5C2', 'Q8I6U8', 'Q08853', 'Q76NM6', 'Q8I3T9', 'Q8I0X2', 'Q8IM16', 'Q7KQM4', 'Q9N623', 'C0H4V6', 'Q8I5G6', 'C6S3C7', 'Q7KQL5', 'Q8IKM5', 'Q8IL86', 'Q8IJR6', 'Q8I492', 'C0H4L1', 'Q8IAW0', 'Q76NN7', 'Q8IB72', 'P13827', 'Q8IDD3', 'O77323', 'P46925', 'C0H546', 'Q8I4R5', 'Q8IBN5', 'Q8I487', 'Q8I3X4', 'P50250', 'Q8IJA9', 'Q8IJ60', 'Q8IEN3', 'Q8IDP8', 'Q8I4W4', 'O77361', 'C6KSR5', 'Q02155', 'Q8IBI3', 'Q8IJ74', 'Q8III5', 'Q8IHS5', 'Q8IDP1', 'Q8I5Y3', 'Q8IEM3', 'Q8IE82', 'Q8IDI5', 'Q8IM15', 'C0H5H0', 'Q8ILV2', 'Q8IM74', 'Q8I5H4', 'Q8ID50', 'Q8IE67', 'Q8IL80', 'O96221', 'Q8IIJ9', 'P13830', 'Q9TY94', 'Q8IBS5', 'P38545', 'Q8IB78', 'C0H4X5', 'C0H551', 'Q8IJK8', 'Q8IIR9', 'Q8IIA4', 'Q7KQK0', 'Q8IDV0', 'Q8IKL4', 'Q8ILK3', 'Q8ILE8', 'Q8IKM6', 'Q8IL88', 'C6KT50', 'P02768']",Artenimol is thought to form a reactive carbon radical intermediate which killsP. falciparumthrough alkylation of a wide array of proteins.,[H][C@@]1(C)CC[C@@]2([H])[C@@]([H])(C)[C@@]([H])(O)O[C@]3([H])O[C@]4(C)CC[C@]1([H])[C@]23OO4,"Artemisinins, including Artenimol which is a major active metabolite of many artemisinins, are thought to act via a common mechanism. While the exact mechanism of action is not certain, theories exist as to how artemisinins produce their antimalarial effect.Artemisinins are believed to bind to haem within theP. falciparumparasite,. The source of this haem varies with the life stage of the parasite. When the parasite is in the early ring stage artemisinins are believed to bind haem produced by the parasite's haem biosynthesis pathway. In later stages artemisinins likely bind to haem released by haemoglobin digestion. Once bound to haem, artemisinins are thought to undergo activation involving ferrous iron via reductive scission which splits the endoperoxide bridge to produce a reactive oxygen,. This reactive oxygen is thought to undergo a subsequent intramolecular hydrogen abstraction to produce a reactive carbon radical. The carbon radical is believed to be the source of the drugs potent activity againstP. falciparumby alkylating a wide array of protein targets,,. The nature and magnitude of the effect on specific protein function as a result of this alkylation is unknown.One target which has been the focus of research is the sarco/endoplasmic reticulum Ca+ ATPase pump ofP. falciparum. Artemisinins have been found to irreversably bind to and inhibit this protein at a binding site similar to that of Thapsigargin. The mechanism is likely the same as for other proteins, namely alkylation via the carbon radical intermediate.Artemisinins appear to preferentially collect in infected erythrocytes, concentrating the drug by several hundred-fold compared to uninfected cells. This may play a role in why little alkylation is seen in uninfected erythrocytes.TargetActionsOrganismUActin, cytoplasmic ligandHumansUAlpha-aminoadipic semialdehyde dehydrogenaseligandHumansUAnnexin AligandHumansUATP synthase subunit alpha, mitochondrialligandHumansUATP synthase subunit g, mitochondrialligandHumansUATP synthase subunit O, mitochondrialligandHumansUCalpastatinligandHumansUT-complex protein subunit gammaligandHumansUCofilin-ligandHumansUChloride intracellular channel protein ligandHumansUCysteine and glycine-rich protein ligandHumansUDihydropyrimidinase-related protein ligandHumansUDesmoplakinligandHumansUElongation factor -alpha ligandHumansUAlpha-enolaseligandHumansUFilamin-AligandHumansUAlpha-ketoglutarate-dependent dioxygenase FTOligandHumansUGlucose--phosphate -dehydrogenaseligandHumansUGlyceraldehyde--phosphate dehydrogenase, testis-specificligandHumansUGlucose--phosphate isomeraseligandHumansUHeterogeneous nuclear ribonucleoproteins A/BligandHumansUHeterogeneous nuclear ribonucleoprotein DligandHumansUHeterogeneous nuclear ribonucleoprotein KligandHumansUHeterochromatin protein -binding protein ligandHumansUHeat shock protein beta-ligandHumansURas GTPase-activating-like protein IQGAPligandHumansUFar upstream element-binding protein ligandHumansUL-lactate dehydrogenase A chainligandHumansUL-lactate dehydrogenase B chainligandHumansUGalectin-ligandHumansUMicrotubule-associated protein ligandHumansUMalate dehydrogenase, cytoplasmicligandHumansUPuromycin-sensitive aminopeptidaseligandHumansUProfilin-ligandHumansUPhosphoglycerate kinase ligandHumansUPyruvate kinase PKMligandHumansUPeptidyl-prolyl cis-trans isomerase AligandHumansUPeroxiredoxin-ligandHumansUS ribosomal protein LligandHumansUS ribosomal protein LligandHumansUS ribosomal protein LligandHumansUS ribosomal protein LaligandHumansUS ribosomal protein LligandHumansUS ribosomal protein LligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUS ribosomal protein SligandHumansUSplicing factor ligandHumansUSplicing factor, proline- and glutamine-richligandHumansUSmall nuclear ribonucleoprotein Sm DligandHumansUSignal recognition particle kDa proteinligandHumansUSerine/arginine-rich splicing factor ligandHumansUTransgelinligandHumansUTransgelin-ligandHumansUTriosephosphate isomeraseligandHumansUTropomyosin alpha- chainligandHumansUTubulin alpha-A chainligandHumansUVimentinligandHumansUZyxinligandHumansUHeat shock cognate kDa proteinligandHumansUTubulin beta- chainligandHumansUTubulin beta-A chainligandHumansUTubulin beta chainligandHumansUFructose-bisphosphate aldolase AligandHumansUGlyceraldehyde--phosphate dehydrogenaseligandHumansUCytochrome cligandHumansUPhosphoglycerate mutase ligandHumansUMyosin-ligandHumansUProtein disulfide-isomeraseligandHumansUProbable ATP-dependent RNA helicase DDXligandHumansUSerine hydroxymethyltransferase, mitochondrialligandHumansUSpliceosome RNA helicase DDXBligandHumansUNucleophosminligandHumansUTranslationally-controlled tumor protein homologligandPlasmodium falciparum (isolate D)UP-type Ca+-transporting ATPaseantagonistPlasmodium falciparumUOrnithine aminotransferaseligandPlasmodium falciparum (isolate D)UElongation factor -alphaligandPlasmodium falciparum (isolate K / Thailand)UMultidrug resistance proteinligandPlasmodium falciparum (isolate FC / Papua New Guinea)UElongation factor ligandPlasmodium falciparum (isolate D)UActin-ligandPlasmodium falciparum (isolate HB)UGlyceraldehyde--phosphate dehydrogenaseligandPlasmodium falciparum (isolate D)UFructose-bisphosphate aldolaseligandPlasmodium falciparumUCell division cycle protein homologue,putativeligandPlasmodium falciparum (isolate D)UHeat shock protein ligandPlasmodium falciparum (isolate D)UEukaryotic initiation factor AligandPlasmodium falciparum (isolate D)UPyruvate kinaseligandPlasmodium falciparum (isolate D)UL-lactate dehydrogenaseligandPlasmodium falciparum (isolate CDC / Honduras)UProtein disulfide-isomeraseligandPlasmodium falciparum (isolate D)UThioredoxin-related protein, putativeligandPlasmodium falciparum (isolate D)USpermidine synthaseligandPlasmodium falciparum (isolate D)UProbable ATP-dependent -phosphofructokinaseligandPlasmodium falciparum (isolate D)UGlutamate dehydrogenaseligandPlasmodium falciparum (isolate D)UEndoplasmin homolog, putativeligandPlasmodium falciparum (isolate D)UHypoxanthine-guanine-xanthine phosphoribosyltransferaseligandPlasmodium falciparum (isolate FCR- / Gambia)UEnolaseligandPlasmodium falciparum (isolate D)US ribosomal protein SligandPlasmodium falciparum (isolate D)UNon-SERCA-type Ca+-transporting P-ATPaseligandPlasmodium falciparum (isolate D)UTubulin alpha chainligandPlasmodium falciparum (isolate K / Thailand)UKnob-associated histidine-rich proteinligandPlasmodium falciparumUS-adenosylmethionine synthaseligandPlasmodium falciparum (isolate D)UV-type H(+)-translocating pyrophosphatase, putativeligandPlasmodium falciparum (isolate D)US ribosomal protein LligandPlasmodium falciparum (isolate D)UPhosphoethanolamine N-methyltransferaseligandPlasmodium falciparum (isolate D)US ribosomal protein SaligandPlasmodium falciparum (isolate D)UConserved Plasmodium membrane proteinligandPlasmodium falciparum (isolate D)US ribosomal protein LligandPlasmodium falciparum (isolate D)UHigh molecular weight rhoptry protein ligandPlasmodium falciparum (isolate D)USerine repeat antigen ligandPlasmodium falciparumUS ribosomal protein SligandPlasmodium falciparum (isolate D)UGlycophorin-binding proteinligandPlasmodium falciparum (isolate D)UCalcium-transporting ATPaseligandPlasmodium falciparum (isolate K / Thailand)UV-type proton ATPase catalytic subunit AligandPlasmodium falciparum (isolate D)US ribosomal protein LligandPlasmodium falciparum (isolate D)UAcyl-CoA synthetaseligandPlasmodium falciparum (isolate D)UPlasmepsin IVligandPlasmodium falciparum (isolate D)UPlasmepsin-ligandPlasmodium falciparum (isolate D)UChloroquine resistance transporterligandPlasmodium falciparumU-- proteinligandPlasmodium falciparum (isolate D)UIsoleucine--tRNA ligase, putativeligandPlasmodium falciparum (isolate D)UPlasmodium exported proteinligandPlasmodium falciparum (isolate D)UTubulin beta chainligandPlasmodium falciparum (isolate D)US ribosomal protein LligandPlasmodium falciparum (isolate D)USec, putativeligandPlasmodium falciparum (isolate D)UAutophagy-related protein , putativeligandPlasmodium falciparum (isolate D)UMature parasite-infected erythrocyte surface antigenligandPlasmodium falciparum (isolate D)UImportin-, putativeligandPlasmodium falciparum (isolate D)UImportin subunit alphaligandPlasmodium falciparum (isolate D)UPeptidyl-prolyl cis-trans isomeraseligandPlasmodium falciparum (isolate D)UDnaJ protein, putativeligandPlasmodium falciparum (isolate D)UMerozoite surface protein ligandPlasmodium falciparum (isolate CDC / Honduras)UGlutamate--tRNA ligaseligandPlasmodium falciparum (isolate D)UT-complex protein subunit etaligandPlasmodium falciparum (isolate D)UPlasmepsin-ligandPlasmodium falciparumUChaperone, putativeligandPlasmodium falciparum (isolate D)URhoptry neck protein ligandPlasmodium falciparum (isolate D)US ribosomal protein S, putativeligandPlasmodium falciparum (isolate D)USkeleton-binding protein ligandPlasmodium falciparum (isolate D)UPurine nucleotide phosphorylase, putativeligandPlasmodium falciparum (isolate D)UAdenosylhomocysteinaseligandPlasmodium falciparum (isolate D)UAdenosine deaminaseligandPlasmodium falciparum (isolate D)UMethionine--tRNA ligaseligandPlasmodium falciparum (isolate D)UCarbamoyl phosphate synthetaseligandPlasmodium falciparum (isolate D)UAspartate carbamoyltransferaseligandPlasmodium falciparum (isolate D)USignal recognition particle receptor, beta subunitligandPlasmodium falciparum (isolate D)UParasite-infected erythrocyte surface proteinligandPlasmodium falciparum (isolate D)UCoatomer alpha subunit, putativeligandPlasmodium falciparum (isolate D)UHexokinaseligandPlasmodium falciparumUProteasome subunit alpha typeligandPlasmodium falciparum (isolate D)UHaloacid dehalogenase-like hydrolaseligandPlasmodium falciparum (isolate D)UInsulinase, putativeligandPlasmodium falciparum (isolate D)US ribosomal protein SligandPlasmodium falciparum (isolate D)UUbiquitin-conjugating enzyme EligandPlasmodium falciparum (isolate D)UEukaryotic translation initiation factor subunit CligandPlasmodium falciparum (isolate D)US ribosomal protein L, putativeligandPlasmodium falciparum (isolate D)US ribosomal protein LligandPlasmodium falciparum (isolate D)US ribosomal protein L, putativeligandPlasmodium falciparum (isolate D)UHAP proteinligandPlasmodium falciparum (isolate D)UHeat shock protein , putativeligandPlasmodium falciparum (isolate D)US ribosomal protein L, putativeligandPlasmodium falciparum (isolate D)ULysophospholipase, putativeligandPlasmodium falciparum (isolate D)UPolyadenylate-binding proteinligandPlasmodium falciparum (isolate D)UUbiquitin-S ribosomal protein LligandPlasmodium falciparum (isolate D)UPhosphoribosylpyrophosphate synthetaseligandPlasmodium falciparum (isolate D)UThioredoxin peroxidase ligandPlasmodium falciparum (isolate D)UProtein transport protein SECligandPlasmodium falciparum (isolate D)UDipeptidyl aminopeptidase ligandPlasmodium falciparum (isolate D)URing-infected erythrocyte surface antigenligandPlasmodium falciparum (isolate FC / Papua New Guinea)UATP-dependent RNA helicase UAPligandPlasmodium falciparum (isolate D)UCalcium-dependent protein kinase ligandPlasmodium falciparum (isolate D)UGTP-binding nuclear protein RanligandPlasmodium falciparumUNucleoside transporter ligandPlasmodium falciparum (isolate D)UAnamorsin homologligandPlasmodium falciparum (isolate D)UGlutamine synthetase, putativeligandPlasmodium falciparum (isolate D)US ribosomal protein Le, putativeligandPlasmodium falciparum (isolate D)UCasein kinase , alpha subunitligandPlasmodium falciparum (isolate D)UThreonine--tRNA ligaseligandPlasmodium falciparum (isolate D)UcAMP-dependent protein kinase regulatory subunitligandPlasmodium falciparum (isolate D)UElongation factor -gamma, putativeligandPlasmodium falciparum (isolate D)UThioredoxin-like proteinligandPlasmodium falciparum (isolate D)US ribosomal protein LligandPlasmodium falciparum (isolate D)US ribosomal protein L, putativeligandPlasmodium falciparum (isolate D)UInner membrane complex sub-compartment protein ligandPlasmodium falciparum (isolate D)UHSP, subfamily A, putativeligandPlasmodium falciparum (isolate D)UPyridoxal '-phosphate synthase subunit PdxligandPlasmodium falciparum (isolate D)USerum albuminligandHumans",[],"['Anti-Infective Agents', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Artemisia', 'Artemisinin and derivatives', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Free Radicals', 'Peroxides', 'Reactive Oxygen Species', 'Sesquiterpenes', 'Terpenes', 'UGT1A9 Substrates', 'UGT2B7 substrates']" +DB09078,Lenvatinib,"Lenvatinibis a receptor tyrosine kinase inhibitor used for the treatment of metastatic thyroid cancer, advanced renal cell carcinoma in combination with everolimus, and unresectable hepatocellular carcinoma.","['P17948', 'P35968', 'P35916', 'P11362', 'P21802', 'P22607', 'P22455', 'P16234', 'P07949', 'P10721']","Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5'-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways.",COC1=C(C=C2C(OC3=CC=C(NC(=O)NC4CC4)C(Cl)=C3)=CC=NC2=C1)C(N)=O,"Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR (FLT), VEGFR (KDR), and VEGFR (FLT). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR, , , and ; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.TargetActionsOrganismAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAVascular endothelial growth factor receptor inhibitorHumansAFibroblast growth factor receptor inhibitorHumansAFibroblast growth factor receptor inhibitorHumansAFibroblast growth factor receptor inhibitorHumansAFibroblast growth factor receptor inhibitorHumansAPlatelet-derived growth factor receptor alphainhibitorHumansAProto-oncogene tyrosine-protein kinase receptor RetinhibitorHumansAMast/stem cell growth factor receptor KitinhibitorHumans",[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Substrates', 'Benzene Derivatives', 'BSEP/ABCB11 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2B6 Inhibitors', 'Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Kinase Inhibitor', 'Moderate Risk QTc-Prolonging Agents', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'OCT2 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protein Kinase Inhibitors', 'QTc Prolonging Agents', 'Receptor Tyrosine Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB00839,Tolazamide,Tolazamideis a sulfonylurea used in the treatment of non insulin dependent diabetes mellitus.,"['Q09428', 'Q14654']","Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.",CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1,"Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.TargetActionsOrganismASulfonylurea receptor , Kir.blockerHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Hypoglycemia-Associated Agents', 'Insulin Secretagogues', 'Oral Hypoglycemics', 'Sulfonamides', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB01264,Darunavir,Darunaviris a HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV) infection in patients with history of prior antiretroviral therapies.,['Q72874'],"Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease, which prevents HIV viral replication.17When administered with ritonavir in combination antiretroviral therapy, darunavir significantly decreases viral load and increases CD4 cell counts, decreasing the morbidity and mortality of HIV infection.2,5,8",[H][C@@]12CCO[C@]1([H])OC[C@@H]2OC(=O)N[C@@H](CC1=CC=CC=C1)[C@H](O)CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1,"The HIV- protease enzyme is necessary for viral precursor protein processing and viral maturation in preparation for infection, and is therefore a target for antiretroviral therapy for HIV. Protease inhibitors are used as a part of highly active antiretroviral therapy (HAART) in patients diagnosed with HIV infection. It has been shown to effectively suppress the virus, leading to significantly decreased morbidity and mortality rates.Darunavir, a HIV protease inhibitor, prevents HIV replication through binding to the enzyme, stopping the dimerization and the catalytic activity of HIV- protease. In particular, it inhibits the cleavage of HIV encoded Gag-Pol proteinsin cells that have been infected with the virus, halting the formation of mature virus particles, which spread the infection. The close contact that darunavir makes with the primary chains of the active site amino acids (Asp- and Asp-) on the protease likely contributes to its potency and efficacy against resistant variants of HIV-.Darunavir is known to bind to different sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer. Darunavir can adapt to changes in the shape of a protease enzyme due to its molecular flexibility.,TargetActionsOrganismAHuman immunodeficiency virus type proteaseinhibitorHuman immunodeficiency virus ",[],"['Amides', 'Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Antivirals used in combination for the treatment of HIV infections', 'Carbamates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Experimental Unapproved Treatments for COVID-19', 'Furans', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'HIV Protease Inhibitors', 'Hyperglycemia-Associated Agents', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Viral Protease Inhibitors']" +DB14011,Nabiximols,"Nabiximols (tradename Sativex®) is a whole plant extract from the Cannabis speciesCannabis sativa L.that has been purified into the active components CBD (cannabidiol) and THC (delta-9-tetrahydrocannabinol). For trademark purposes, purified CBD is branded as Nabidiolex®, while THC is purified as the product Tetrabinex®. Sativex® is available in a 1:1 formulation of THC:CBD as an oro-mucosal pump spray used for treatment of neuropathic pain from Multiple Sclerosis (MS) and for intractable cancer pain. Although still largely debated, Cannabis has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity1,2.","['P21554', 'P34972', 'P47775', 'P23415', 'P23415', 'P48167', 'O75311', 'Q14330', 'Q9Y2T6', 'P08908', 'P28223', 'P36544', 'P41143', 'P35372', 'P37231', 'Q8NER1', 'O43497', 'O95180', 'Q9P0X4', 'O75762', 'Q7Z2W7', 'Q9Y5S1', 'Q8NET8', 'Q9HBA0', 'P21796', 'P23219', 'P35354', 'P24752', 'P05093', 'P04035', 'P00390', 'P07203', 'P14902', 'F1T0I5', 'Q16678', 'P20815', 'P10635', 'P05177', 'P04798', 'P24462', 'Q08257', 'P04040', 'O00519', 'P00441', 'Q02083']","The principal pharmacological effects of THC include analgesic, muscle relaxant, antiemetic, appetite stimulant and psychoactive effects. CBD has analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant and anti-psychotic activity.",[H][C@]1(CCC(C)=C[C@@]1([H])C1=C(O)C=C(CCCCC)C=C1O)C(C)=C.[H][C@@]12CCC(C)=C[C@@]1([H])C1=C(O)C=C(CCCCC)C=C1OC2(C)C,"The primary psychoactive component of Cannabis, delta -tetrahydrocannabinol (Δ-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid- (CBR) and Cannabinoid- (CBR) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body. Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects.There is further evidence that CBD also activates -HTA serotonergic and TRPV– vanilloid receptors, antagonizes alpha- adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca stores, blocks low-voltage-activated (T-type) Ca channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH),.TargetActionsOrganismACannabinoid receptor Not AvailableHumansACannabinoid receptor Not AvailableHumansUG-protein coupled receptor inverse agonistHumansUGlycine receptor subunit alpha-Not AvailableHumansUGlycine receptor (alpha-/beta)Not AvailableHumansUGlycine receptor subunit alpha-Not AvailableHumansUN-arachidonyl glycine receptorNot AvailableHumansUG-protein coupled receptor Not AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumansU-hydroxytryptamine receptor ANot AvailableHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUDelta-type opioid receptorNot AvailableHumansUMu-type opioid receptorNot AvailableHumansUPeroxisome proliferator-activated receptor gammaNot AvailableHumansUTransient receptor potential cation channel subfamily V member Not AvailableHumansUVoltage-dependent T-type calcium channel subunit alpha-GNot AvailableHumansUVoltage-dependent T-type calcium channel subunit alpha-HNot AvailableHumansUVoltage-dependent T-type calcium channel subunit alpha-INot AvailableHumansUTransient receptor potential cation channel subfamily A member Not AvailableHumansUTransient receptor potential cation channel subfamily M member Not AvailableHumansUTransient receptor potential cation channel subfamily V member Not AvailableHumansUTransient receptor potential cation channel subfamily V member Not AvailableHumansUTransient receptor potential cation channel subfamily V member Not AvailableHumansUVoltage-dependent anion-selective channel protein Not AvailableHumansUProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumansUAcetyl-CoA acetyltransferase, mitochondrialinhibitorHumansUSteroid -alpha-hydroxylase/, lyaseinhibitorHumansU-hydroxy--methylglutaryl-coenzyme A reductasestimulatorHumansUGlutathione reductase, mitochondrialstimulatorHumansUGlutathione peroxidase stimulatorHumansUIndoleamine ,-dioxygenase inhibitorHumansUArylalkylamine N-acetyltransferaseinhibitorHumansUCytochrome P BinhibitorHumansUCytochrome P AinhibitorHumansUCytochrome P DsubstrateinhibitorHumansUCytochrome P AinhibitorHumansUCytochrome P AinhibitorHumansUCytochrome P AinhibitorHumansUQuinone oxidoreductaseinhibitorHumansUCatalaseinhibitorHumansUFatty-acid amide hydrolase inhibitorinducerHumansUSuperoxide dismutase [Cu-Zn]inhibitorHumansUN-acylethanolamine-hydrolyzing acid amidaseinhibitorHumans",[],"['Agents producing tachycardia', 'Analgesics', 'BCRP/ABCG2 Inhibitors', 'Cannabinoid Receptor Agonists', 'Cannabinoids and similars', 'Central Nervous System Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Peripheral Nervous System Agents', 'Pharmaceutical Preparations', 'Sensory System Agents', 'Terpenes']" +DB01135,Doxacurium chloride,"Doxacurium chlorideis a nondepolarizing neuromuscular blocking agent used as an adjunct to general anesthesia to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgical procedures.","['Q15822', 'P08172']","Doxacurium chloride is a long-acting, nondepolarizing skeletal muscle relaxant. The neuromuscular block produced by doxacurium chloride may be antagonized by anticholinesterase agents. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at reversal, the longer the time and the greater the dose of anticholinesterase required for recovery of neuromuscular function. Doxacurium chloride is approximately 2.5 to 3 times more potent than pancuronium and 10 to 12 times more potent than metocurine.",COC1=CC(CC2C3=C(OC)C(OC)=C(OC)C=C3CC[N+]2(C)CCCOC(=O)CCC(=O)OCCC[N+]2(C)CCC3=CC(OC)=C(OC)C(OC)=C3C2CC2=CC(OC)=C(OC)C(OC)=C2)=CC(OC)=C1OC,"Doxacurium chloride binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in a block of neuromuscular transmission (non-depolarizing). This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-antagonistHumansUMuscarinic acetylcholine receptor MantagonistHumans",[],"['Anticholinergic Agents', 'Central Nervous System Depressants', 'Cholinesterase substrates', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Muscarinic Antagonists', 'Muscle Relaxants', 'Muscle Relaxants, Peripherally Acting Agents', 'Musculo-Skeletal System', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular-Blocking Agents (Nondepolarizing)', 'Nicotinic Antagonists', 'Peripheral Nervous System Agents']" +DB04871,Lorcaserin,"Lorcaserinis a serotonin 2C receptor agonist used in conjunction with physical activity and calorie restriction for weight loss in obese patients with a body mass index (BMI) of 30 and above, and in overweight patients with weight-related comorbidities.",['P28335'],Lorcaserin produced a dose-dependent weight loss over a 12-week period by promoting satiety and decreasing food consumption.,C[C@H]1CNCCC2=CC=C(Cl)C=C12,"Although the exact mechanism is unknown, it is believed to involve the selective activation of -HTC receptors in the anorexigenic pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus. This results in decreased food intake and satiety by promoting the release of alpha-melanocortin stimulating hormone, which acts on melanocortin- receptors.TargetActionsOrganismU-hydroxytryptamine receptor CNot AvailableHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'Antiobesity Preparations, Excl. Diet Products', 'Central Nervous System Depressants', 'Centrally Acting Antiobesity Products', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 2c Receptor Agonists', 'Serotonin 5-HT2 Receptor Agonists', 'Serotonin 5-HT2C Receptor Agonists', 'Serotonin Agents', 'Serotonin Modulators', 'Serotonin Receptor Agonists']" +DB00324,Fluorometholone,"Fluorometholoneis an ophthalmic corticosteroid used for the relief of inflammation located in both the palpebral and bulbar conjunctiva, the cornea, and the anterior segment of the globe of the eye.",['P04150'],"Corticosteroids such as fluorometholone inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.",[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C,"There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A. Their primary target is the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Agents for Treatment of Hemorrhoids and Anal Fissures for Topical Use', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Allergic Agents', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Moderately Potent (Group II)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Ophthalmologicals', 'Pregnadienediols', 'Pregnadienes', 'Pregnanes', 'Sensory Organs', 'Steroids', 'Steroids, Fluorinated', 'Thyroxine-binding globulin inhibitors', 'Vasoprotectives']" +DB00896,Rimexolone,Rimexoloneis a glucocorticoid used to treat inflammation of the eye.,['P04150'],"Rimexolone is a glucocorticoid corticosteroid for systemic use. Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They inhibit edema, cellular infiltration, capillary dilatation, fibroblastic proliferation, deposition of collagen and scar formation associated with inflammation.",[H][C@@]12C[C@@H](C)[C@](C)(C(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Rimexolone is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A inhibitory proteins which, through inhibition of arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. By binding to the glucocorticoid receptor, this drug ultimately leads to changes in genetic transcription involving the lipocortins and prostaglandins.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids for Systemic Use, Plain', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Ophthalmologicals', 'Pregnanes', 'Sensory Organs', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins', 'Thyroxine-binding globulin inhibitors']" +DB06202,Lasofoxifene,"Lasofoxifene is a non-steroidal 3rd generation selective estrogen receptor modulator (SERM) that selectively binds to both ERα and ERβ with high affinity. It is a naphthalene derivative marketed for prevention and treatment of osteoporosis and for the treatment of vaginal atrophy. It was initially developed as Oporia by Pfizer as a treatment for postmenopausal osteoporosis and vaginal atrophy, in which were both rejected for approval by FDA. Later Fablyn was developed as a result of a research collaboration between Pfizer and Ligand Pharmaceuticals with a newly submitted New Drug Application in 2008. It gained approval by European Commission in March 2009. Ligand Pharmaceuticals signed a license agreement with Sermonix Pharmaceuticals for the development and commercialization of oral lasofoxifene in the USA.","['P03372', 'Q92731', 'P34972']","Lasofoxifene exhibits both significant estrogenic and antiestrogenic activity both in vitro and in vivo, targeting any tissues that possess ERs, such as bone, uterus, breast, blood vessels, and liver. Binding assays demonstrated high affinity of the compound for both ERα and ERβ in a tissue-dependent manner. It mimics the effects of estradiol with varying agonist and antagonist effects.",[H][C@@]1(CCC2=CC(O)=CC=C2[C@@]1([H])C1=CC=C(OCCN2CCCC2)C=C1)C1=CC=CC=C1,"Lasofoxifene mediates an agonist effect on estrogen receptors expressed on bone to mimic the positive effects of estrogen to reduce the production and lifespan of osteoclasts via altering the NF-kappaB ligand (RANKL)/RANK/osteoprotegerin system, stimulation of osteoblast (the bone forming cells) activity and additional effects on calcium homeostasis. It acts as an antagonist at uterus and mammary glandsby suppressing the estrogen signaling in oncogenic pathways and inhibits the downstream gene transcription. +A study also suggests that lasofoxifene may also act as an inverse agonist at CB cannabinoid receptor which is expressed in bone to inhibit osteoclast formation and resorptive activity.TargetActionsOrganismAEstrogen receptor alphaantagonistagonistnegative modulatorHumansAEstrogen receptor betaagonistHumansUCannabinoid receptor inverse agonistHumans",[],"['Genito Urinary System and Sex Hormones', 'Naphthalenes', 'Selective Estrogen Receptor Modulators', 'Sex Hormones and Modulators of the Genital System']" +DB01466,Ethylmorphine,Ethylmorphineis an opioid analgesic and antitussive agent used to reduce coughs caused by colds and lung infections in combination with codeine.,['P35372'],"Ethylmorphine is metabolized by the enzyme cytochrome P450 2D6 to morphine. Morphine is a narcotic pain management agent indicated for the relief of pain in patients who require opioid analgesics for more than a few days. Morphine interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Morphine appears to increase the patient's tolerance for pain and to decrease discomfort, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Opioids also produce respiratory depression by direct action on brain stem respiratory centers.",[H][C@@]12OC3=C(OCC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O,"Ethylmorphine is metabolized by the liver enzyme cytochrome P D to morphine. The precise mechanism of the analgesic action of morphine is unknown. However, specific CNS opiate receptors have been identified and likely play a role in the expression of analgesic effects. Morphine first acts on the mu-opioid receptors. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation. +It has been shown that morphine binds to and inhibits GABA inhibitory interneurons. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.TargetActionsOrganismAMu-type opioid receptoragonistHumans",[],"['Alkaloids', 'Analgesics', 'Antitussive Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cough and Cold Preparations', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Morphinans', 'Morphine Derivatives', 'Narcotics', 'Ophthalmologicals', 'Opiate Alkaloids', 'Opioids', 'Opium Alkaloids and Derivatives', 'Peripheral Nervous System Agents', 'Phenanthrenes', 'Respiratory System Agents', 'Sensory Organs', 'Sensory System Agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome']" +DB00868,Benzonatate,Benzonatateis a non-narcotic oral antitussive drug used to suppress coughing.,['Q14524'],"Benzonatate suppresses cough associated with both acute and chronic respiratory conditions. Its works by desensitizing the pulmonary stretch receptors involved in the cough reflex. There are limited clinical trials of benzonatate; however, earlier studies demonstrated inhibition of experimentally-induced cough and subjectively-measured pathological cough by benzonatate.1Benzonatate has no inhibitory effects on the respiratory center in recommended dosage. Its onset of action is within 15 to 20 minutes following administration and its duration of effect is about 3 to 8 hours.7",CCCCNC1=CC=C(C=C1)C(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOC,"Benzonatate is a local anesthetic drug that acts peripherally by anesthetizing and reducing the activity of vagal stretch receptors or nerve fibres located in the respiratory passages, lungs, and pleura.,Once the stretch receptors are stimulated, they send impulses to the cough centre located in the medulla via an afferent pathway consisting of sensory nerve fibres or the vagus nerve. The efferent signal is then generated that sends impulses to the expiratory muscles to produce a cough.Anesthetizing these receptors by benzonatate results in the inhibition of the cough reflex activity and cough production.,Benzonatate also inhibits the transmission of impulses of the cough reflex in the vagal nuclei of the medulla.There are several proposed mechanisms of benzonatate; it is also a potent voltage-gated sodium channel inhibitor.TargetActionsOrganismUSodium channel protein type subunit alphaantagonistHumans",[],"['Alkanes', 'Amines', 'Antitussive Agents', 'Butanes', 'Central Nervous System Agents', 'Cholinesterase substrates', 'Cough and Cold Preparations', 'Decreased Tracheobronchial Stretch Receptor Activity', 'Hydrocarbons, Acyclic', 'Non-narcotic Antitussive', 'Respiratory System Agents']" +DB09099,Somatostatin,"Somatostatinis a natural peptide hormone used to treat acute bleeding from esophageal varices, gastrointestinal ulcers, and gastritis; prevent pancreatic complications after surgery; and restrict secretions of the upper intestine, pancreas, and biliary tract.","['P30872', 'P30874', 'P32745', 'P31391', 'P35346']","Somatostatin is an endogenous peptide hormone that is secreted by the central nervous system, gastrointestinal tract, retina, peripheral neurons and pancreatic D cells of the islets of Langerhans. It exhibits several biological roles but predominantly exerts an inhibitory effect on secretion of other hormones and transmitters1. While distribution of two active isoforms of somatostatin is similar, SST-14 is more predominant in the enteric neurons and peripheral nerves whereas SST-28 is more prominent in the retina and intestinal mucosal cells1.Anterior pituitary gland and brain:It inhibits the release of growth hormones and thyroid-stimulating hormones, such as thyroid stimulating hormone (TSH) and thyrotrophin, from the anterior pituitary while inhibiting the release of dopamine from the midbrain, norepinephrine, TRH and corticotrophin-releasing hormone in the brain1.Pancreas:In the pancreas, somatostatin reduces the secretion of glucagon and insulin as well as bicarbonate ions and other enzymes1,9.Thyroid gland:Somatosatin reduces secretion of T3, T4, and calcitonin1. Somatostatin regulates the thyroid function by reducing basal TSH release9.Gastrointestinal tract:It attenuates the release of most gastrointestinal hormones such as gastrin, secretin, motilin, gastric acid, enteroglucagon, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), intrinsic factor, pepsin, neurotensin, as well as bile secretion and colonic fluid secretion1.Adrenal gland:It inhibits angiotensin II-stimulated aldosterone secretion and acetylcholine-induced medullary catecholamine secretion1.Eye/retina:Somatostatin inhibits the production of vascular endothelial growth factor1.Inflammatory cells and sensory nerves:The expression of somatostatin has been found in inflammatory cells such as lymphocytes, monocytes, macrophages and endothelial cells to act as an autocrine or paracrine regulator in local immune responses. Findings suggest that somatostatin may play a role in exerting local and systemic anti-inflammatory and antinociceptive effects1. On primary afferent neurons, somatostatin reduces the responses to thermal stimulation in C-mechanoheat sensitive fibers in a dose-dependent fashion and reduces the responses of C-mechanoheat fibers to bradykinin-induced excitation and sensitization to heat6. Somatostatin is reported to elicit an analgesic effect when applied intrathecally; there is evidence supporting that similar effects may occur when systemically used to treat endocrine disorders9.Somatostatin is thought to reduce bleeding from esophageal varices by causing splanchnic vasoconstriction2. Somatostatin elicits anti-neoplastic actions on various tumours via direct or indirect effects, or a combination of both4.",C[C@@H](O)[C@@H]1NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CO)NC1=O)C(O)=O)NC(=O)CNC(=O)[C@H](C)N)[C@@H](C)O,"Somatostatin binds to subtypes of somatostatin receptors (SSTRs), which are all Gi-protein-coupled transmembrane receptors that inhibits adenylyl cyclase upon activation. By inhibiting intracellular cyclic AMP and Ca+ and by a receptor-linked distal effect on exocytosis, SSTRs block cell secretion. The common pathway shared by the receptors involve the activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK). With the exception of SSTR, activation of SSTRs lead to activation of voltage-gated potassium channels accompanied by increased K+ currents. This result in membrane hyperpolarization and inhibits depolarization-induced Ca+ influx through voltage-sensitive Ca+ channels. Depending on the receptor subtype, signalling cascades involve activation of other downstream targets such as Na+/H+ exchanger, Rho GTPase, and nitric oxide synthase (NOS). SSTRs to bind both somatostatin isoforms with equal nanomolar binding affinity whereas SSTR exhibits a - to -fold higher binding affinity for SST-.Effects of SSTR:Upon biding of somatostatin and activation, SSTR mediates an antisecretory effect on growth hormone, prolactin and calcitonin.Effects of SSTR:SSTR subtype dominates in endocrine tissues. By binding to SST receptors, somatostatin exerts paracrine inhibitory actions on gastrin release from G cells, histamine release from ECL cells, and directly on parietal cell acid output. SSTR receptor signalling cascades also inhibit the secretion of growth hormone and that of adrenocorticotropin, glucagon, insulin, and interferon-γ.Effects of SSTR:Activation of these receptors lead to reduction in cell proliferation. SSTR triggers PTP-dependent cell apoptosis accompanied by activation of p and the pro-apoptotic protein Bax. A study of the matrigel sponge assay suggests that through SSTR-mediated inhibition of both NOS and MAPK activities may lead to the antitumor effects of somatostatin in inhibiting tumor angiogenesis.Effects of SSTR:The functions of SSTR remain largely unknown.Effects of SSTR:Like SSTR, SSTR subtype also predominates in endocrine tissues. Upon activation, SSTR signalling cascades exert an inhibitory action on growth hormone, adrenocorticotropin, insulin, and glucagon-like peptide- as well as the secretion of amylase.The presence of somatostatin receptors has been identified in most neuroendocrine tumours, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. The antitumor effects of somatostatin were also effective in various malignant lymphomas and breast tumours. Gastrointestinal hormones, such as gastrin, secretin, and cholecystokinin (CCK), as well as growth hormones and growth factors are thought to be elevated in gastrointestinal tract and neuroendocrine tumours and are inhibited by somatostatin.In vitro, somatostatin inhibited epidermal growth factor (EGF)-induced DNA synthesis and replication following which suggest that somatostatin may have direct anti-proliferative effects via SSTR signalling. Acromegaly is characterized as the endocrine disorder caused by a functioning tumour of cells that secrete growth hormone from the anterior pituitary. Somatostatin analogue therapies serve to normalize the elevated levels of GH and insulin-like growth factor (IGF-) and attenuate tumour growth.In the vascular system this likely produces vasoconstriction by inhibiting adenylate cyclase leading to a lowering the concentration of cyclic adenosine monophosphate in the endothelial cells which ultimately blocks vasodilation through this pathway. This vasoconstriction is though the be responsible for reducing blood flow to the esophageal tissues and so reduces bleeding from esophageal varices.Somatostatin mediates an analgesic activity by reducing vascular and nociceptive components of inflammation. Studies indicate that somatostatin may be present in nociceptive DRG neurons with C-fibers and primary afferent neurons to inhibit the release of transmitters at the presynaptic junctions of the sensory-efferent nerve terminals. Exogenous somatostatin has shown to inhibit the release of Substance P from central and peripheral nerve ending.TargetActionsOrganismASomatostatin receptor type agonistHumansASomatostatin receptor type agonistHumansASomatostatin receptor type agonistHumansASomatostatin receptor type agonistHumansASomatostatin receptor type agonistHumans",['Restriction of Secretions'],"['Amino Acids, Peptides, and Proteins', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Hypothalamic Hormones', 'Nerve Tissue Proteins', 'Neuropeptides', 'P-glycoprotein substrates', 'Pancreatic Hormones', 'Peptide Hormones', 'Peptides', 'Pituitary and Hypothalamic Hormones and Analogues', 'Pituitary Hormone Release Inhibiting Hormones', 'Proteins', 'Somatostatin and Analogues', 'Somatostatin, agonists', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB00710,Ibandronate,Ibandronateis a bisphosphonate used to treat osteoporosis in postmenopausal women.,"['O95749', 'P14324']","Ibandronate is a nitrogen containing bisphosphonate used to treat and prevent osteoporosis in postmenopausal women.11,12The therapeutic index is wide as overdoses are not especially toxic, and the duration of action is long as the half life can be up to 157 hours.11,12Patients should be counselled regarding the risk of upper GI adverse reactions, hypocalcemia, musculoskeletal pain, osteonecrosis of the jaw, atypical fractures of the femur, and severe renal impairment.11,12",CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O,"Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis.Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.Osteoclasts mediate resorption of bone.When osteoclasts bind to bone they form podosomes, ring structures of F-actin.Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.Nitrogen containing bisphosphonates such as ibandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate.,These components are essential for post-translational prenylation of GTP-binding proteins like Rap.The lack of prenylation of these proteins interferes with their function, and in the case of Rap, leads to apoptosis.ibandronate also activated caspase- which contribute to apoptosis.TargetActionsOrganismAHydroxylapatiteantagonistHumansAGeranylgeranyl pyrophosphate synthaseinhibitorHumansAFarnesyl pyrophosphate synthaseinhibitorHumans",[],"['Agents Causing Muscle Toxicity', 'Bisphosphonates', 'Bone Density Conservation Agents', 'Drugs Affecting Bone Structure and Mineralization', 'Drugs for Treatment of Bone Diseases', 'Musculo-Skeletal System', 'Organophosphonates', 'Organophosphorus Compounds', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB11640,Amifampridine,Amifampridineis a voltage gated potassium channel blocker used to treat Lambert-Eaton myasthenic syndrome.,['Q09470'],"Administration of amifampridine to patients with LES in clinical trials resulted in improvement of the compound muscle action potential (CMAP), muscle function, and quantitative myasthenia gravis (QMG) score1. One case of a slight prolongation of the QTc interval in male patient with LEMS and euthyroid Hashimoto’s disease treated with 90 mg of amifampridine in combination with 100 mg azathioprine was reported1.In vitro, amifampridine was shown to modulate cardiac conduction and induce phasic contractions in different arteries from several species1. In addition, it stimulated potassium-evoked dopamine and noradrenaline release in rat hippocampal slices and upregulate acetylcholine release in the brain1. It may also potentiate adrenergic and cholinergic neuromuscular transmission in the gatrointestinal tract1. In a single pharmacokinetic study, no effect was observed of amifampridine phosphate on cardiac repolarization as assessed using the QTc interval12. There were no changes in heart rate, atrioventricular conduction or cardiac depolarization as measured by the heart rate, PR and QRS interval durations12.",NC1=CC=NC=C1N,"Amifampridine is a symptomatic treatment that increases acetylcholine concentrations at the neuromuscular junction. It selectively blocks presynaptic fast voltage-gated potassium channels, thereby prolonging cell membrane depolarization and action potential, and augmenting calcium transport into the nerve endings. Increased intracellular calcium enhances the exocytosis of acetylcholine-containing vesicles and enhances impulse transmission at central, autonomic, and neuromuscular synapses,. Amifampridine improves muscle strength and resting compound muscle action potential (CMAP) amplitudes with an overall weighted mean difference of . mV.TargetActionsOrganismAPotassium voltage-gated channel subfamily A member blockerHumans",[],"['Amines', 'Aminopyridines', 'Membrane Transport Modulators', 'Miscellaneous Central Nervous System Agents', 'Moderate Risk QTc-Prolonging Agents', 'OCT2 Inhibitors', 'Peripheral Nervous System Agents', 'Potassium Channel Blockers', 'Pyridines', 'QTc Prolonging Agents']" +DB01245,Decamethonium,Decamethonium is used in anesthesia to cause paralysis. It is a short acting depolarizing muscle relaxant. It is similar to acetylcholine and acts as a partial agonist of the nicotinic acetylcholine receptor.,"['Q15822', 'P43681', 'P17787', 'P22303']","Decamethonium acts as a depolarizing muscle relaxant or neuromuscular blocking agent. It acts as an agonist of nicotinic acetycholine receptors in the motor endplate and causes depolarization. This class of drugs has its effect at the neuromuscular junction by preventing the effects of acetylcholine. Normally, when a nerve stimulus acts to contract a muscle, it releases acetylcholine. The binding of this acetylcholine to receptors causes the muscle to contract. Muscle relaxants play an important role in anesthesia even though they don't provide any pain relief or produce unconsciousness.",C[N+](C)(C)CCCCCCCCCC[N+](C)(C)C,"Binds to the nicotinic acetycholine receptors (by virtue of its similarity to acetylcholine) in the motor endplate and blocks access to the receptors. In the process of binding, the receptor is actually activated - causing a process known as depolarization. Since it is not degraded in the neuromuscular junction, the depolarized membrance remains depolarized and unresponsive to any other impulse, causing muscle paralysis.TargetActionsOrganismANeuronal acetylcholine receptor subunit alpha-partial agonistHumansUNeuronal acetylcholine receptor subunit alpha-Not AvailableHumansUNeuronal acetylcholine receptor subunit beta-Not AvailableHumansUAcetylcholinesteraseinhibitorHumans",[],"['Amines', 'Bis-Trimethylammonium Compounds', 'Central Nervous System Depressants', 'Cholinesterase Inhibitors', 'Neuromuscular Agents', 'Neuromuscular Blocking Agents', 'Neuromuscular Depolarizing Agents', 'Neurotoxic agents', 'Onium Compounds', 'Peripheral Nervous System Agents', 'Quaternary Ammonium Compounds']" +DB08806,Roxatidine acetate,Roxatidine acetate is a specific and competitive H2 receptor antagonist. It is currently approved in South Africa under the tradename Roxit.,['P25021'],"Roxatidine acetate suppresses the effect of histamine on the parietal cells of the stomach (H2-receptor antagonist). This suppressive action is dose-dependent. As a result, the production and secretion, particularly of gastric acid, are reduced. Roxatidine acetate has no antiandrogenic effects and does not influence drug-metabolizing enzymes in the liver.",CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1,"The H antagonists are competitive inhibitors of histamine at the parietal cell H receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: histamine released by ECL cells in the stomach is blocked from binding on parietal cell H receptors which stimulate acid secretion, and other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H receptors are blocked.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Acid Reducers', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H2 Antagonists', 'Neurotransmitter Agents']" +DB00194,Vidarabine,Vidarabineis an antiviral agent used to treat various viral infections.,"['P04293', 'P09250', 'Q9QNF7']","Vidarabine is a synthetic purine nucleoside analogue within vitroandin vivoinhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of Vidarabine is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts Vidarabine into Vidarabine monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes.In vitro, Vidarabine triphosphate stops the DNA replication of herpes virus by being incorporated into the DNA strand and preventing the formation of phosphodiester bridges between bases. This ultimately leads to destabilization of the viral DNA strands.",NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O,"Vidarabine stops replication of herpes viral DNA in ways: ) competitive inhibition of viral DNA polymerase, and consequently ) incorporation into and termination of the growing viral DNA chain. +Vidarabine is sequentially phosphorylated by kinases to the triphosphate ara-ATP, which is the active form of vidarabine that acts as both an inhibitor and a substrate of viral DNA polymerase. By acting as a substrate for viral DNA polymerase, ara-ATP competitively inhibits dATP leading to the formation of ‘faulty’ DNA. Ara-ATP can also be incorporated into the DNA strand to replace many of the adenosine bases, resulting in the disruption of DNA synthesis.TargetActionsOrganismADNA polymerase catalytic subunitinhibitorHHV-AThymidine kinaseinducerAThymidine kinaseinducerHHV-",[],"['Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antimetabolites', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Arabinonucleosides', 'Carbohydrates', 'Direct Acting Antivirals', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring', 'Noxae', 'Nucleic Acids, Nucleotides, and Nucleosides', 'Nucleosides', 'Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors', 'Ophthalmologicals', 'Purine Nucleosides', 'Purines', 'Ribonucleosides', 'Sensory Organs', 'Toxic Actions']" +DB01606,Tazobactam,"Tazobactamis a beta lactamase inhibitor administered with antibiotics such as piperacillin and ceftolozane to prevent their degradation, resulting in increased efficacy.","['P62594', 'P18251', 'P0AD63']","Tazobactam inhibits the action of bacterial beta-lactamase producing organisms, which are normally resistant to beta-lactam antibiotics. This augments the effects of antibiotics which would otherwise not be effective in treating certain infections. These antibiotics contain a beta-lactam ring in their chemical structure, which is destroyed by beta-lactam resistant organisms.4When combined with other antibiotics, a variety of infections, including serious and life-threatening infections may be treated.14,11",[H][C@@]12CC(=O)N1[C@@H](C(O)=O)[C@](C)(CN1C=CN=N1)S2(=O)=O,"Tazobactam broadens the spectrum of piperacillinand ceftolozaneby making them effective against organisms that express beta-lactamase and would normally degrade them. This occurs through the irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes. Tazobactam is predominantly effective against the OHIO-, SHV-, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases.,,Tazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone.TargetActionsOrganismABeta-lactamase TEMinhibitorSalmonella typhiABeta-lactamase Ohio-inhibitorEnterobacter cloacaeABeta-lactamase SHV-inhibitorEscherichia coli",[],"['Amides', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Aza Compounds', 'Azabicyclo Compounds', 'Beta-Lactam Antibacterials', 'beta-Lactamase Inhibitors', 'beta-Lactams', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT1/SLC22A6 inhibitors', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Sulfones', 'Sulfur Compounds']" +DB00748,Carbinoxamine,"Carbinoxamineis a first generation antihistamine used to treat allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, allergic reactions, and mild allergic reactions.",['P35367'],"Carbinoxamine is a first generation antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, carbinoxamine competes with free histamine for binding at HA-receptor sites. Carbinoxamine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of carbinoxamine.",CN(C)CCOC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1,"Carbinoxamine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Carbinoxamine's anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown.TargetActionsOrganismAHistamine H receptorantagonistHumans",[],"['Aminoalkyl Ethers', 'Antihistamines for Systemic Use', 'Central Nervous System Depressants', 'Drugs causing inadvertant photosensitivity', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Moderate Risk QTc-Prolonging Agents', 'Neurotransmitter Agents', 'Photosensitizing Agents', 'QTc Prolonging Agents']" +DB01412,Theobromine,"Theobromine (3,7-dimethylxanthine) is the principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than theophylline and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)","['P30542', 'P29274', 'Q07343']","Theobromine, a xanthine derivative like caffeine and the bronchodilator theophylline, is used as a CNS stimulant, mild diuretic, and respiratory stimulant (in neonates with apnea of prematurity).",CN1C=NC2=C1C(=O)NC(=O)N2C,"Theobromine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic ′,′-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine and theobromine act as antagonist at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of xanthine derivatives such as theobromine and caffeine. Blockade of the adenosine A receptor in the heart leads to the accelerated, pronounced ""pounding"" of the heart upon caffeine intake.TargetActionsOrganismAAdenosine receptor AantagonistHumansAAdenosine receptor AaantagonistHumansUcAMP-specific ','-cyclic phosphodiesterase BinhibitorHumans",[],"['Alkaloids', 'Anti-Asthmatic Agents', 'Autonomic Agents', 'Bronchodilator Agents', 'Cardiovascular Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 Substrates', 'Diuretics', 'Drugs for Obstructive Airway Diseases', 'Heterocyclic Compounds, Fused-Ring', 'Low-Ceiling Diuretics, Excl. Thiazides', 'Peripheral Nervous System Agents', 'Purines', 'Purinones', 'Respiratory System Agents', 'Vasodilating Agents', 'Xanthine derivatives']" +DB11219,Enzacamene,Enzacameneis an ingredient used in sunscreen to block UVB radiation.,"['P06401', 'P10275', 'Q92731', 'P03372']","Several studies suggest that enzacamene elicit estrogen-like effects. In prepubertal male rats exposed to enzacamene during embryonic and fetal development, decrease in testicular weight with decreased levels of LH, GnRH, and glutamate were observed; in comparison, there was an increase in LH, GnRH, and aspartate levels in peripubertal rats2. These findings suggest that high concentrations of enzacamene during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage2. In a study of zebrafish (Danio rerio) embryo, exposure to enzacamene during early vertebrate development was associated with muscular and neuronal defects that may result in developmental defects, including a reduction in AChE activity, disorganized pattern of slow muscle fibers, and axon pathfinding errors during motor neuron innervation5. Enzacamene displays a weak binding activity in receptors binding assays using the mammalian estrogen receptor (ER)4.",CC1=CC=C(\C=C2/C3CCC(C)(C2=O)C3(C)C)C=C1,"Enzacamene absorbs UV-B rays. It is proposed that enzacamene exerts estrogen-like activities in the same direction as endogenous estrogens via nonclassical estrogen signaling mechanisms that do not involve gene regulation by the nuclear ER. It binds to cytosolic estradiol binding sites of estrogen receptors with low to moderate affinity compared to that of the endogenous agonist. Based on the findings of a study withXenopushepatocytes in culture, enzacamene has a potential to induce the ER gene only at higher concentrations (– μmol/L). While enzacamene was not shown to activate estrogen-dependent gene transcription when tested in an ER reporter gene assay in yeast cells, it was demonstrated inXenopushepatocytes cultures that activate ER-dependent signaling mechanisms leading to altered gene expression. In micromolar concentrations, enzacamene accelerates cell proliferation rate in MCF- human breast cancer cells.TargetActionsOrganismUProgesterone receptorantagonistHumansUAndrogen receptorantagonistHumansUEstrogen receptor betaNot AvailableHumansUEstrogen receptor alphaNot AvailableHumans",[],"['Bicyclic Monoterpenes', 'Bornanes', 'Bridged-Ring Compounds', 'Ketones', 'Monoterpenes', 'Norbornanes', 'Sunscreen Agents', 'Terpenes']" +DB11577,Indigotindisulfonic acid,Indigotindisulfonic acidis a medication used to visualize ureteral orifices during cystoscopy and ureteral catheterization.,"['P35348', 'P35368', 'P25100', 'P08913', 'P18089', 'P18825']","Approximately 4-9 minutes after indigotindisulfonate sodium is administered intravenously, its blue color is detectable at the ureteral orifices, enabling easier visualization for accuracy during medical procedures.10Although indigotindisulfonic acid and its salt form indigotindisulfonate sodium were initially acknowledged as pharmacologically inert, their use has been associated with cardiovascular effects.1,2Indigotindisulfonate sodium may lead to transient alpha-receptor stimulation, manifested as increased total peripheral vascular resistance, increased diastolic and systolic blood pressure, and increased central venous pressure with decreased cardiac output, stroke volume and heart rate.1The use of indigotindisulfonate sodium may lead to severe or life-threatening cardiovascular reactions such as cardiac arrest, arrhythmia, asystole, second-degree atrioventricular block, hypotension, elevation in blood pressure, bradycardia, and tachycardia.10Serious anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, or erythema have also been reported.10Also, the use of indigotindisulfonate sodium may interfere with light absorption and pulse oximetric methods.10",OS(=O)(=O)C1=CC2=C(N\C(C2=O)=C2\NC3=C(C=C(C=C3)S(O)(=O)=O)C2=O)C=C1,"Indigotindisulfonic acid is a biologically inert blue dye.After intravenous injection, indigotindisulfonic acid is excreted by the kidney through tubular secretion and, with its deep blue color, it enhances visualization of the ureteral orifices.Because of this, indigotindisulfonic acid is used to identify ureteral patency in urologic and gynecologic procedures.Indigotindisulfonic acid may lead to the development of hypertension. It has been suggested that indigotindisulfonic acid inhibits endothelium-dependent relaxation at the level of nitric oxide generation and/or its release from the endothelium. Also, indigotindisulfonic acid appears to inhibit vascular guanylyl cyclase in smooth muscle.TargetActionsOrganismNAlpha adrenergic receptoragonistHumans",[],"['Coloring Agents', 'Compounds used in a research, industrial, or household setting', 'Diagnostic Agents', 'Diagnostic Dye', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Indoles', 'Tests for Renal Function and Ureteral Injuries']" +DB04884,Dapoxetine,Dapoxetineis a selective serotonin reuptake inhibitor used in the treatment of premature ejaculation.,"['P08908', 'P28222', 'P28335']","Dapoxetine is a selective serotonin reuptake inhibitor currently undergoing trials through Alza (under license from GenuPro, a collaboration between Eli Lilly and PPD). Dapoxetine is a short-acting SSRI drug currently being considered for approval by the Food and Drug Administration (FDA) for the treatment of premature ejaculation in men, which would make it the first drug approved for such treatment. Despite two clinical trials finished in 2006, experts doubt it will be approved by the FDA soon because SSRIs come with undesirable side-effects after long-term use, such as psychiatric problems, dermatological reactions, increase in body weight, lower sex-drive, nausea, headache, upset stomach and weakness, thus not significantly outweighing the benefit of premature ejaculation medication versus the risks. By contrast with SSRIs approved for depression, which take 2 weeks or longer to reach steady-state concentration, dapoxetine has a unique pharmacokinetic profile, with a short time to maximum serum concentration (about 1 h) and rapid elimination (initial half-life of 1-2 h).",CN(C)[C@@H](CCOC1=CC=CC2=CC=CC=C12)C1=CC=CC=C1,"The drug's mechanism of action is thought to be related to inhibition of neuronal reuptake of serotonin and subsequent potentiation of serotonin activity. The central ejaculatory neural circuit comprises spinal and cerebral areas that form a highly interconnected network. The sympathetic, parasympathetic, and somatic spinal centers, under the influence of sensory genital and cerebral stimuli integrated and processed at the spinal cord level, act in synergy to command physiologic events occurring during ejaculation. Experimental evidence indicates that serotonin (-HT), throughout brain descending pathways, exerts an inhibitory role on ejaculation. To date, three -HT receptor subtypes (-HT(A), -HT(B), and -HT(C)) have been postulated to mediate -HT's modulating activity on ejaculation.TargetActionsOrganismU-hydroxytryptamine receptor ANot AvailableHumansU-hydroxytryptamine receptor BNot AvailableHumansU-hydroxytryptamine receptor CNot AvailableHumans",[],"['Amines', 'Antidepressive Agents', 'Benzene Derivatives', 'Benzyl Compounds', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (weak)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Genito Urinary System and Sex Hormones', 'Hypoglycemia-Associated Agents', 'Selective Serotonin Reuptake Inhibitors', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin Agents', 'Serotonin Modulators', 'Urologicals']" +DB06772,Cabazitaxel,Cabazitaxelis an antineoplastic agent used in combination with corticosteroids to treat metastatic castration-resistant prostate cancer in patients previously treated with a docetaxel-containing treatment regimen.,['Q9H4B7'],"Cabazitaxel demonstrates a broad spectrum of antitumour activity against advanced human tumours xenografted in mice, including intracranial human glioblastomas.6Cabazitaxel has a low affinity to P-glycoprotein, allowing it to penetrate the blood-brain barrier without being subject to extensive P-gp-mediated active efflux.3,4Cabazitaxel works against docetaxel-sensitive tumours and tumour models resistant to docetaxel and other chemotherapy drugs.4,6",[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C4=CC=CC=C4)C(C)=C([C@@H](OC)C(=O)[C@]1(C)[C@H](C[C@H]1OC[C@@]21OC(C)=O)OC)C3(C)C,"Microtubules are cytoskeletal polymers that regulate cell shape, vesicle transport, cell signalling, and cell division. They are made up of alpha-tubulin and beta-tubulin heterodimers. Microtubules extend toward the mitotic spindle during mitosis to allow the separation and distribution of chromosomes during cell division.Cabazitaxel binds to the N-terminal amino acids of the beta-tubulin subunit and promotes microtubule polymerization while simultaneously inhibiting disassembly: this results in the stabilization of microtubules, preventing microtubule cell division. Cabazitaxel ultimately blocks mitotic and interphase cellular functions and tumour proliferation.,TargetActionsOrganismATubulin beta- chaininhibitorHumans",[],"['Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Cardiotoxic antineoplastic agents', 'Cyclodecanes', 'Cycloparaffins', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Diterpenes', 'Immunosuppressive Agents', 'Microtubule Inhibition', 'Microtubule Inhibitors', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'OATP1B3 inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Taxane Derivatives', 'Taxoids', 'Terpenes']" +DB00665,Nilutamide,Nilutamideis an antineoplastic hormone used to treat prostate cancer.,['P10275'],"Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide.",CC1(C)NC(=O)N(C1=O)C1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F,"Nilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.TargetActionsOrganismAAndrogen receptorantagonistHumans",[],"['Androgen Receptor Antagonists', 'Androgen Receptor Inhibitors', 'Antiandrogens', 'Antiandrogens, non-steroidal', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Imidazoles']" +DB05812,Abiraterone,Abirateroneis an antiandrogen used in the treatment of metastatic castration-resistant prostate cancer and metastatic high-risk castration-sensitive prostate cancer.,['P05093'],"In vivo, abiraterone acetate is rapidly hydrolyzed to abiraterone, which mediates its pharmacological actions.1Abiraterone decreases serum testosterone and other androgens. A change in serum prostate-specific antigen (PSA) levels may be observed.9",[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C,"α-hydroxylase/C,-lyase (CYP) is a key enzyme in androgen biosynthesis. It is primarily expressed in testicular, adrenal, and prostatic tumours. CYP catalyzes the α-hydroxylation of pregnenolone and progesterone to their α-hydroxy derivative, followed by subsequent cleavage of the C ,-acetyl group to yield dehydroepiandrosterone (DHEA) and androstenedione. DHEA and androstenedione are precursors of testosterone.,Aberrant androgen levels and unregulated androgen receptor signalling have been implicated in the development and progression of various prostate cancers.Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumour.,Abiraterone inhibits CYP to block androgen production. Inhibition of CYP can also result in increased mineralocorticoid production by the adrenals.TargetActionsOrganismASteroid -alpha-hydroxylase/, lyaseinhibitorHumans",[],"['Androstanes', 'Androstenes', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP1A2 Inhibitors (strong)', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C8 Inhibitors', 'Cytochrome P-450 CYP2C8 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C8 Inhibitors (weak)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (moderate)', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Cytochrome P450 17A1 Inhibitors', 'Endocrine Therapy', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Hormone Antagonists', 'Hormone Antagonists and Related Agents', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'Steroid Synthesis Inhibitors', 'Steroids']" +DB08801,Dimetindene,Dimetindeneis a 1st generation selective H1 antagonist used topically as an antipruritic and orally to treat allergies.,"['P35367', 'P08172']","Dimethindene occurs as a racemic mixture. The (S)-(+)-dimethindene is a potent M2-selective muscarinic receptor antagonist (with lower affinity for M1, M3, and M4 muscarinic receptors). The (R)-(-)-enantiomer is the eutomer (responsible for bioactivity) for histamine H1 receptor binding.",CC(C1=C(CCN(C)C)CC2=CC=CC=C12)C1=CC=CC=N1,"Dimethindene is a selective histamine H antagonist and binds to the histamine H receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.TargetActionsOrganismAHistamine H receptorantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anti-Allergic Agents', 'Anticholinergic Agents', 'Antihistamines for Systemic Use', 'Antihistamines for Topical Use', 'Antipruritics', 'Antipruritics, Incl. Antihistamines, Anesthetics, Etc.', 'Dermatologicals', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Indenes', 'Muscarinic Antagonists', 'Neurotransmitter Agents', 'Pyridines', 'Substituted Alkylamines']" +DB01260,Desonide,Desonideis a topical corticosteroid used for the symptomatic treatment of inflammatory and pruritic manifestations of corticosteroid responsive dermatoses.,['P04150'],Desonide is a synthetic nonfluorinated corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents.,[H][C@@]12C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C,"Like other topical corticosteroids, desonide has anti-inflammatory, antipruritic and vasoconstrictive properties. The drug binds to cytosolic glucocorticoid receptors. This complex migrates to the nucleus and binds to genetic elements on the DNA. This activates and represses various genes. However corticosteroids are thought to act by the induction of phospholipase A inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Moderately Potent (Group II)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Immunosuppressive Agents', 'Ophthalmologicals', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Sensory Organs', 'Steroids']" +DB00799,Tazarotene,"Tazaroteneis an acetylenic retinoid used to treat fine wrinkles, mottled pigmentation of the skin, acne vulgaris, and plaque psoriasis.","['P10276', 'P28702', 'P13631', 'P10826']","Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles.",CCOC(=O)C1=CN=C(C=C1)C#CC1=CC2=C(SCCC2(C)C)C=C1,"Although the exact mechanism of tazarotene action is not known, studies have shown that the active form of the drug (tazarotenic acid) binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARb, and RARg, but shows relative selectivity for RARb, and RARg and may modify gene expression. It also has affinity for RXR receptors.TargetActionsOrganismARetinoic acid receptor alphaagonistHumansARetinoic acid receptor RXR-betaagonistHumansARetinoic acid receptor gammaagonistHumansARetinoic acid receptor betaagonistHumans",[],"['Antipsoriatics', 'Antipsoriatics for Topical Use', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Keratolytic Agents', 'Misc. Skin and Mucous Membrane Agents', 'Noxae', 'Prodrugs', 'Pyridines', 'Retinoids', 'Teratogens', 'Toxic Actions']" +DB11157,Anthralin,Anthralinis an anthracene used to treat stable plaque psoriasis.,"['P35908', 'Q99456', 'Q9UQF2']","Anthralin is a natural anthraquinone derivative, anti-psoriatic and anti-inflammatory agent. It controls skin growth by reducing the synthesis of DNA and the mitotic activity in the hyperplastic epidermis, normalizing the rate of cell proliferation and keratinization10.",OC1=CC=CC2=C1C(=O)C1=C(O)C=CC=C1C2,"Anthralin inhibits the proliferation of keratinocytes (epidermal skin cells), prevents the action of T-cells, and promotes cell differentiation, likely through mitochondrial dysfunction. In addition, the production of free radicals may contribute to its anti-psoriatic effect. In vitro studies demonstrate that anthralin prolongs the prophase component of mitosis for keratinocytes and leukocytes. Prophase is the first step of mitosis, the process separating the duplicated genetic material carried in the nucleus of a parent cell into two identical daughter cells. In vivo studies demonstrate that anthralin blocks DNA synthesis and can increase the release of reactive oxygen species.Anthralin is believed to normalize the rate of epidermal cell proliferation and keratinization by reducing the mitotic activity of the epidermal hyperplasia in psoriasis.Anti-proliferative and anti-inflammatory effects of anthralin have been demonstrated on both psoriatic and healthy skin. The anti-proliferative effects of anthralin are thought to be due to a combination of inhibition of DNA synthesis and its strong reducing properties. The effectiveness of anthralin as an anti-psoriatic agent is partly owed to its ability to promote lipid peroxidation and reduce the concentration of endothelial adhesion molecules, which are found to be elevated in psoriatic patients,.Recent studies suggest that its ability to prevent T-lymphocyte activation and normalize keratinocyte differentiation may occur by a direct effect on mitochondria.TargetActionsOrganismAKeratin, type II cytoskeletal epidermalantagonistHumansAKeratin, type I cytoskeletal antagonistHumansUC-Jun-amino-terminal kinase-interacting protein agonistHumans",[],"['Anthracenes', 'Antipsoriatics', 'Antipsoriatics for Topical Use', 'Antracen Derivatives', 'Dermatologicals']" +DB08877,Ruxolitinib,"Ruxolitinibis a kinase inhibitor used to treat various types of myelofibrosis, polycythemia vera in patients who have not responded to or cannot tolerate hydroxyurea, and to treat graft-versus-host disease in cases that are refractory to steroid treatment.","['O60674', 'P23458', 'P52333', 'P29597']","Ruxolitinib is an antineoplastic agent that inhibits cell proliferation, induces apoptosis of malignant cells, and reduces pro-inflammatory cytokine plasma levels by inhibiting JAK-induced phosphorylation of signal transducer and activator of transcription (STAT).4Inhibition of STAT3 phosphorylation, which is used as a marker of JAK activity,2by ruxolitinib is achieved at two hours after dosing which returned to near baseline by 10 hours in patients with myelofibrosis and polycythemia vera.16In clinical trials, ruxolitinib reduced splenomegaly and improved symptoms of myelofibrosis.4In a mouse model of myeloproliferative neoplasms, administration of ruxolitinib was associated with prolonged survival.2Ruxolitinib inhibits both mutant and wild-type JAK24; however, JAK2V617F mutation, which is often seen in approximately 50% of patients with myelofibrosis, was shown to reduce ruxolitinib sensitivity, which may also be associated with possible resistance to JAK inhibitor treatment.14",N#CC[C@H](C1CCCC1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1,"The Janus kinase (JAK) family of protein tyrosine kinases comprises JAK, JAK, JAK, and non-receptor tyrosine kinase (TYK).JAKs play a pivotal role in intracellular signalling pathways of various cytokines and growth factors essential to hematopoiesis, such as interleukin, erythropoietin, and thrombopoietin.JAKs have diverse functions: JAK and JAK promote lymphocyte differentiation, survival, and function, while JAK promotes signal transduction of erythropoietin and thrombopoietin.,JAKs are in close proximity to the cytokine and growth factor receptor’s cytoplasmic region. Upon binding of cytokines and growth factors, JAKs are activated, undergoing cross-phosphorylation and tyrosine phosphorylation. This process also reveals selective binding sites for STATs, which are DNA-binding proteins that also bind to the cytoplasmic region of cytokine or growth factor receptors. Activated JAKs and STATs translocate to the nucleus as transcription factors to regulate gene expression of pro-inflammatory cytokines such as IL-, IL-, and nuclear factor κB (NF-κB).They also activate downstream pathways that promote erythroid, myeloid, and megakaryocytic development.The molecular pathogenesis of myeloproliferative neoplasms is not fully understood; however, JAK is constitutively activated and the JAK-STAT signalling pathway becomes deregulated and aberrant.,Ruxolitinib is a selective and potent inhibitor of JAK and JAK, with some affinity against JAK and TYK. Anticancer effects of ruxolitinib are attributed to its inhibition of JAKs and JAK-mediated phosphorylation of STAT.By downregulating the JAK-STAT pathway, ruxolitinib inhibits myeloproliferation and suppresses the plasma levels of pro-inflammatory cytokines such as IL- and TNF-α.Activated JAKs are also implicated in graft-versus-host-disease (GVHD), which is a severe immune complication of allogeneic hematopoietic cell transplantation GVHD is associated with significant morbidity and mortality, especially for patients who do not respond well to corticosteroid therapy. Activated JAKS stimulate T-effector cell responses, leading to increased proliferation of effector T cells and heightened production of pro-inflammatory cytokines. By blocking JAK and JAk, ruxolitinib inhibits donor T-cell expansion and suppresses pro-inflammatory responses.TargetActionsOrganismATyrosine-protein kinase JAKinhibitorHumansATyrosine-protein kinase JAKinhibitorHumansATyrosine-protein kinase JAKinhibitorHumansANon-receptor tyrosine-protein kinase TYKinhibitorHumans",[],"['Agents for Dermatitis, Excluding Corticosteroids', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'Cancer immunotherapy', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Immunosuppressive Agents', 'Immunotherapy', 'Janus Kinase Inhibitor', 'Janus Kinases, antagonists & inhibitors', 'Kinase Inhibitor', 'Myelosuppressive Agents', 'Narrow Therapeutic Index Drugs', 'Protein Kinase Inhibitors', 'Tyrosine Kinase Inhibitors']" +DB01581,Sulfamerazine,"Sulfamerazineis an antibacterial agent used in the treatment of various bacterial infections, such as bronchitis, prostatitis, and urinary tract infections.",['P0AC13'],"Sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis in bacteria.",CC1=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=NC=C1,Sulfamerazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamerazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA.TargetActionsOrganismADihydropteroate synthaseinhibitorEscherichia coli (strain K),[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Benzene Derivatives', 'Benzenesulfonamides', 'Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Long-Acting Antibacterial Sulfonamides', 'Sulfanilamides', 'Sulfonamide Antibacterial', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds']" +DB01415,Ceftibuten,"Ceftibutenis a third-generation cephalosporin antibiotic commonly used in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsillitis.","['P0AD68', 'P02918', 'P02919', 'P0AD65']",Ceftibuten is an antibiotic with bactericidal actions.,[H][C@]12SCC=C(N1C(=O)[C@H]2NC(=O)C(=C/CC(O)=O)\C1=CSC(N)=N1)C(O)=O,Ceftibuten exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall. This binding leads to inhibition of cell-wall synthesis.TargetActionsOrganismAPeptidoglycan synthase FtsIinhibitorEscherichia coli (strain K)APenicillin-binding protein AinhibitorEscherichia coli (strain K)APenicillin-binding protein BinhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorEscherichia coli (strain K),[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'OAT1/SLC22A6 Substrates', 'OAT3/SLC22A8 Inhibitors', 'OAT3/SLC22A8 Substrates', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00311,Ethoxzolamide,"Ethoxzolamide is a sulfonamide used as diuretic and in glaucoma. It inhibits carbonic anhydrase activity in proximal renal tubules to decrease reabsorption of water, sodium, potassium, bicarbonate. Its pharmacological activity thus confers the risk for hypokalemia.","['P00918', 'P22748', 'P43166', 'P00915', 'P07451']","Ethoxzolamide is an inhibitor of the carbonic anhydrase enzyme in proximal renal tubules that works by decreasing the reabsorption of water, sodium, potassium, bicarbonate. It also decreases the activity of carbonic anhydrase expressed in the CNS, which leads to increased seizure threshold. Inhibition of carbonic anhydrase in the eye contributes to its effect of reducing intraocular pressure and decreasing aqueous humor.",CCOC1=CC2=C(C=C1)N=C(S2)S(N)(=O)=O,"Ethoxzolamide binds to and inhibits carbonic anhydrase I, which plays an essential role in facilitating the transport of CO and H+ in the intracellular space, across biological membranes, and in the layers of the extracellular space. Through inhibition of the enzyme, the balance of applicable membrane equilibrium systems are affected.TargetActionsOrganismACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Amides', 'Benzothiazoles', 'Carbonic Anhydrase Inhibitors', 'Diuretics', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Natriuretic Agents', 'OAT1/SLC22A6 inhibitors', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds', 'Thiazoles']" +DB00705,Delavirdine,Delavirdineis a non-nucleoside reverse transcriptase inhibitor used to treat HIV infection.,['Q72547'],"Delavirdine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Delavirdine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of Delavirdine does not compete with template or nucleoside triphosphates. HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by Delavirdine.",CC(C)NC1=C(N=CC=C1)N1CCN(CC1)C(=O)C1=CC2=C(N1)C=CC(NS(C)(=O)=O)=C2,Delavirdine binds directly to viral reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by disrupting the enzyme's catalytic site.TargetActionsOrganismAReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ,[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (strong)', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strong)', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inhibitors', 'Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP3A7 Inhibitors', 'Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor', 'Indoles', 'Non-Nucleoside Reverse Transcriptase Inhibitors', 'Nonnucleoside Reverse Transcriptase Inhibitors', 'Nucleic Acid Synthesis Inhibitors', 'Piperazines', 'Reverse Transcriptase Inhibitors']" +DB00138,Cystine,"Cystineis an oxidated derivative of the amino acid cysteine found in various nutritional products, acne treatments, and creams to treat cervical injury or inflammation.","['Q9UPY5', 'O60931']","L-Cystine is a covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Cystine is a chemical substance which naturally occurs as a deposit in the urine, and can form a calculus (hard mineral formation) when deposited in the kidney. The compound produced when two cysteine molecules linked by a disulfide (S-S) bond. Cystine is required for proper vitamin B6 utilization and is also helpful in the healing of burns and wounds, breaking down mucus deposits in illnesses such as bronchitis as well as cystic fibrosis. Cysteine also assists in the supply of insulin to the pancreas, which is needed for the assimilation of sugars and starches. It increases the level of glutathione in the lungs, liver, kidneys and bone marrow, and this may have an anti-aging effect on the body by reducing age-spots etc.",N[C@@H](CSSC[C@H](N)C(O)=O)C(O)=O,"Certain conditions, e.g. an acetaminophen overdose, deplete hepatic glutathione and subject the tissues to oxidative stress resulting in loss of cellular integrity. L-Cystine serves as a major precursor for synthesis of glutathione.TargetActionsOrganismUCystine/glutamate transporterNot AvailableHumansUCystinosinNot AvailableHumans",['Nutritional supplementation'],"['Amino Acids', 'Amino Acids, Diamino', 'Amino Acids, Dicarboxylic', 'Amino Acids, Peptides, and Proteins', 'Amino Acids, Sulfur', 'Anions', 'Cysteine', 'Dietary Supplements', 'Disulfides', 'Electrolytes', 'Hydrogen Sulfide', 'Ions', 'Sulfides', 'Sulfur Compounds', 'Supplements']" +DB09223,Blonanserin,"Blonanserin is an atypical antipsychotic approved in Japan in January, 2008. It offers improved tolerability as it lacks side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As a second-generation (atypical) antipsychotic, it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics.","['P14416', 'P35462', 'P28223']",Blonanserin antagonizes dopamine and serotonin receptors to reduce symptoms of schizophrenia2.,CCN1CCN(CC1)C1=NC2=C(CCCCCC2)C(=C1)C1=CC=C(F)C=C1,"Blonanserin binds to and inhibits dopamine receptors D and D as well as the serotonin receptor -HTA with high affinity. Blonanserin has low affinity for other dopamine and serotonin receptors as well as muscarinic, adrenergic, and histamine receptors. This reduces dopaminergic and serotonergic neurotransmission which is thought to produce a reduction in positive and negative symptoms of schizophrenia respectively.TargetActionsOrganismADopamine D receptorantagonistHumansADopamine D receptorantagonistHumansA-hydroxytryptamine receptor AantagonistHumans",[],"['Antidepressive Agents', 'Antipsychotic Agents', 'Antipsychotic Agents (Second Generation [Atypical])', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dopamine Antagonists', 'Dopamine D2 Receptor Antagonists', 'Drugs that are Mainly Renally Excreted', 'Neurotoxic agents', 'Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome', 'Serotonin 5-HT2 Receptor Antagonists', 'Serotonin 5-HT2A Receptor Antagonists', 'Serotonin Agents', 'Serotonin Receptor Antagonists']" +DB00767,Benzquinamide,"Benzquinamide is a discontinued antiemetic compound with antihistaminic, mild anticholinergic, and sedative properties. The mechanism of action is not known, but presumably benzquinamide works via antagonism of muscarinic acetycholine receptors and histamine H1 receptors.","['P35367', 'P08173', 'P11229', 'P08912', 'P08172', 'P20309']","Benzquinamide is an antiemetic compound with antihistaminic, mild anticholinergic, and sedative properties.",CCN(CC)C(=O)C1CN2CCC3=CC(OC)=C(OC)C=C3C2CC1OC(C)=O,"The mechanism of action is not known, but presumably benzquinamide works via antagonism of muscarinic acetycholine receptors and histamine H receptors.TargetActionsOrganismAHistamine H receptorantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumansAMuscarinic acetylcholine receptor MantagonistHumans",[],"['Agents producing tachycardia', 'Anticholinergic Agents', 'Heterocyclic Compounds, Fused-Ring', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Muscarinic Antagonists', 'P-glycoprotein inhibitors']" +DB09119,Eslicarbazepine acetate,Eslicarbazepine acetateis an anticonvulsant agent used as an adjunct to treat partial-onset seizures in patients with inadequate clinical response to conventional antiepileptic therapy.,['Q99571'],Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval.,CC(=O)O[C@H]1CC2=CC=CC=C2N(C(N)=O)C2=CC=CC=C12,"Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity.TargetActionsOrganismAPX purinoceptor antagonistHumans",[],"['Anticonvulsants', 'Carboxamide Derivatives', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Eslicarbazepine and prodrugs', 'Heterocyclic Compounds, Fused-Ring', 'Membrane Transport Modulators', 'Nervous System', 'Sodium Channel Blockers', 'UGT1A1 Substrates', 'Voltage-Gated Sodium Channel Blockers']" +DB05087,Ganaxolone,Ganaxoloneis a neuroactive steroid GABA-A receptor modulator used for the treatment of seizures associated with CDKL5 deficiency disorder (CDD).,"['P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","Ganaxolone - like other neurosteroids - lacks classical hormonal activity, and instead appears to exert its effects directly via modulation of GABAAreceptors.1Similar to other antiepileptic drugs, ganaxolone has been associated with significant somnolence and sedation - patients should be instructed to use caution when operating heavy machinery (e.g. driving).5In addition, antiepileptic drugs may increase the risk of suicidal behaviour and ideation, although this risk has not been documented directly in patients taking ganaxolone.5When considering ganaxolone therapy, clinicians should balance the risk of suicidal thoughts or behaviours with the risk of untreated illness.Ganaxolone drug scheduling is currently under review by the US Drug Enforcement Administration (DEA), but it appears to carry some potential for abuse.5Clinicians should consider assessing for a history of drug abuse when deciding to initiate therapy with ganaxolone.",[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@](C)(O)CC[C@]12C,"Ganaxolone belongs to a novel class of neuroactive steroids sometimes referred to as ""epalons"", which are potent and specific positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors in the central nervous system (CNS).It binds GABAAat one of several potential binding sites, all of which are distinct from the benzodiazepine binding site.By enhancing the inhibitory effects of GABAAreceptors, endogenous and exogenous neurosteroids have been associated with anxiolytic, sedative, and anticonvulsant effects, amongst others.While the precise mechanism of action of ganaxolone in the treatment of seizures associated with CDD is unknown, its anticonvulsant effects are likely due to positive allosteric GABAAmodulationTargetActionsOrganismAGABA(A) Receptorpositive allosteric modulatorHumans",[],"['Anticonvulsants', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'GABA Agents', 'GABA Modulators', 'Nervous System', 'Neuroactive Steroid Gamma-Aminobutyric Acid A Receptor Positive Modulator', 'Neurotransmitter Agents', 'Pregnanes', 'Steroids']" +DB01121,Phenacemide,Phenacemide is used to control certain seizures in the treatment of epilepsy. This medicine acts on the central nervous system (CNS) to reduce the number and severity of seizures.,['P35498'],"Phenacemide is a ureal anticonvulsant indicated for control of severe epilepsy, particularly mixed forms of complex partial (psychomotor or temporal lobe) seizures, refractory to other anticonvulsants. Phenacemide elevates the threshold for minimal electroshock convulsions and abolishes the tonic phase of maximal electroshock seizures. It also prevents or modifies seizures induced by pentylenetetrazol or other convulsants.",NC(=O)NC(=O)CC1=CC=CC=C1,Phenacemide binds to and blocks neuronal sodium channels or voltage sensitive calcium channels. This blocks or suppresses neuronal depolarization and hypersynchronization. Hypersynchronization is what often causes seizures.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans,[],"['Acetamides', 'Amides', 'Anticonvulsants', 'Benzene Derivatives', 'Central Nervous System Depressants', 'Nervous System']" +DB00147,Pyridoxal,"The 4-carboxyaldehyde form of vitamin B 6 which is converted to pyridoxal phosphate which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. [PubChem]",['O00764'],"Pyridoxal principally in the form of the coenzyme pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).",CC1=NC=C(CO)C(C=O)=C1O,"Pyridoxal is the precursor to pyridoxal phosphate. Pyridoxal '-phosphate is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).TargetActionsOrganismAPyridoxal kinaseNot AvailableHumans",[],"['Dietary Supplements', 'Micronutrients', 'Picolines', 'Pyridines', 'Supplements', 'Vitamin B Complex', 'Vitamins']" +DB01299,Sulfadoxine,Sulfadoxineis a long acting sulfonamide used for the treatment or prevention of malaria.,"['Q27738', 'P13922']","Sulfadoxine helps inhibit the enzyme dihydropteroate synthetase which is an enzyme necessary in the conversion of PABA to folic acid. As folic acid is vital to the synthesis, repair, and methylation of DNA which is vital to cell growth in Plasmodium falciparum. With this vital nutrient lacking, the parasite has difficulty in reproducing.",COC1=NC=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=C1OC,"Sulfadoxine is a sulfa drug, often used in combination with pyrimethamine to treat malaria. This medicine may also be used to prevent malaria in people who are living in, or will be traveling to, an area where there is a chance of getting malaria. Sulfadoxine targets Plasmodium dihydropteroate synthase and dihydrofolate reductase. Sulfa drugs or Sulfonamides are antimetabolites. They compete with para-aminobenzoic acid (PABA) for incorporation into folic acid. The action of sulfonamides exploits the difference between mammal cells and other kinds of cells in their folic acid metabolism. All cells require folic acid for growth. Folic acid (as a vitamin) diffuses or is transported into human cells. However, folic acid cannot cross bacterial (and certain protozoan) cell walls by diffusion or active transport. For this reason bacteria must synthesize folic acid from p-aminobenzoic acid.TargetActionsOrganismADihydropteroate synthetaseNot AvailablePlasmodium falciparumUBifunctional dihydrofolate reductase-thymidylate synthaseinhibitorPlasmodium falciparum (isolate K / Thailand)",[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antimalarials', 'Antiparasitic Agents', 'Antiparasitic Products, Insecticides and Repellents', 'Antiprotozoals', 'Benzene Derivatives', 'Benzenesulfonamides', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Long-Acting Antibacterial Sulfonamides', 'Sulfanilamides', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB06201,Rufinamide,Rufinamideis an antiepileptic drug used as adjunctive therapy to treat seizures associated with Lennox-Gastaut Syndrome (LGS).,"['Q15858', 'P41594']",At high concentrations will inhibit action of mGluR5 subtype receptors thus preventing the production of glutamate.,NC(=O)C1=CN(CC2=C(F)C=CC=C2F)N=N1,"Rufinamide is a triazole derivative antiepileptic that prolongs the inactive state of voltage gated sodium channels thus stabilizing membranes, ultimately blocking the spread of partial seizure activity.TargetActionsOrganismUSodium channel protein type subunit alphamodulatorHumansUMetabotropic glutamate receptor inhibitorHumans",[],"['Anticonvulsants', 'Carboxamide Derivatives', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP2E1 Inhibitors', 'Cytochrome P-450 CYP2E1 Inhibitors (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (weak)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Membrane Transport Modulators', 'Miscellaneous Anticonvulsants', 'Nervous System', 'Sodium Channel Blockers', 'Voltage-Gated Sodium Channel Blockers']" +DB09028,Cytisine,Cytisineis an alkaloid with partial agonist activity at the α4β2 nicotinic acetylcholine receptor used to aid smoking cessation.,"['P43681', 'P36544', 'P32297', 'Q15825', 'P17787']","Various models have been run where the affinity of nAChR agonists to the receptor subtype are tested to help identify the molecules, groups and steric conformation that are vital to greater affinity. By using a nAChR muscle receptor subtype (α1)2β1δγ model the following results were obtained: +anatoxin > epibatidine > acetylcholine > DMPP >> CYTISINE > pyrantel > nicotine > coniine > tubocurare > lobeline, +where anatoxin had the highest activity efficacy and tubocurare the lowest. Acetylcholine on the other hand induced a much longer opening time of the receptor though anatoxin is more potent. The results suggest that anatoxin derivatives would be helpful in understanding structure-activity relationships (SAR) for muscle nAChRs (Cooper et al., 1996).",O=C1C=CC=C2[C@H]3CNC[C@H](C3)CN12,"Cytisine is a low efficacy partial agonist of ⍺-β nicotinic acetylcholine receptors. These which are believed to be central to the effect of nicotine (NIC) on the reward pathway and facilitate addiction. Cytisine reduces the effects of NIC on dopamine release in the mesolimbic system when given alone, while simultaneously attenuating NIC withdrawal symptoms that accompany cessation attempts.TargetActionsOrganismUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit alpha-agonistHumansUNeuronal acetylcholine receptor subunit beta-partial agonistHumans",[],"['Alkaloids', 'Drugs Used in Addictive Disorders', 'Drugs Used in Nicotine Dependence', 'Heterocyclic Compounds, Fused-Ring', 'Nervous System', 'Nicotine, antagonists & inhibitors', 'Quinolizidines', 'Quinolizines']" +DB00423,Methocarbamol,"Methocarbamolis a CNS depressant indicated with rest, physical therapy and other treatments to control the discomfort associated with various acute musculoskeletal conditions.",['P00915'],"Methacarbamol is a skeletal muscle relaxant with an unknown mechanism of action.5Methacarbamol has been shown to block spinal polysynaptic reflexes, decrease nerve transmission in spinal and supraspinal polysynaptic pathways, and prolong the refractory period of muscle cells.5,4Methocarbamol does not act as a local anesthetic upon injection.4In animal studies, methocarbamol also prevents convulsions after electric shock.5",COC1=C(OCC(O)COC(N)=O)C=CC=C1,"The mechanism of action of methocarbamol is thought to be dependant on its central nervous system depressant activity.This action may be mediated through blocking spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways, and prolonging the refractory period of muscle cells.,Methocarbamol has been found to have no effect on contraction of muscle fibres, motor end plates, or nerve fibres.TargetActionsOrganismNCarbonic anhydrase inhibitorHumans",[],"['Acids, Acyclic', 'Benzene Derivatives', 'Carbamates', 'Carbamic Acid Esters', 'Catechols', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Centrally-mediated Muscle Relaxation', 'Ethers', 'Methyl Ethers', 'Muscle Relaxants', 'Muscle Relaxants, Centrally Acting Agents', 'Musculo-Skeletal System', 'Peripheral Nervous System Agents', 'Phenols', 'Phenyl Ethers', 'Phenylcarbamates']" +DB00600,Monobenzone,Monobenzoneis a hydroquinone derivative used to treat vitiligo.,['P14679'],"Monobenzone is the monobenzyl ether of hydroquinone. Monobenzone, applied topically to the skin, is used as a depigmenting agent inhibitting melanin produced by polymerization of oxidation products of tyrosine and dihydroxyphenyl compounds. Monobenzone works by permanently removing color from normal skin located around skin with vitiligo.",OC1=CC=C(OCC2=CC=CC=C2)C=C1,"Monobenzone is a depigmenting agent whose mechanism of action is not fully understood. It is proposed that it increases the excretion of melanin from the melanocytes. This effect is erratic and may take one to four months to occur while existing melanin is lost with normal sloughing of the stratum corneum. Hyperpigmented skin appears to fade more rapidly than does normal skin, and exposure to sunlight reduces the depigmenting effect of the drug. Following skin depigmentation after topical application of monobenzone, the histological studies indicate similar results as that seen in vitiligo, where the epidermis is intact but with the absence of identifiable melanocytes.TargetActionsOrganismUTyrosinaseinhibitorHumans",[],"['alpha-Galactosidase, antagonists & inhibitors', 'Benzene Derivatives', 'Depigmenting Agents', 'Dermatologicals', 'Melanin Synthesis Inhibitors', 'Phenols']" +DB00846,Flurandrenolide,Flurandrenolideis a corticosteroid used to treat corticosteroid-responsive dermatoses.,['P04150'],"Flurandrenolide is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions.",CC1(C)O[C@@H]2C[C@H]3[C@@H]4C[C@H](F)C5=CC(=O)CC[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@@]2(O1)C(=O)CO,"Flurandrenolide is a topical corticosteroid. It is normally applied to a plastic tape called Cordran. Cordran is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions. Flurandrenolide, which is slowly released from the Cordran tape, binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin- (annexin-) synthesis, which then binds to cell membranes preventing the phospholipase A from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX- and COX-) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin- escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen). It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Pregnanes', 'Pregnenediones', 'Pregnenes', 'Steroids', 'Steroids, Fluorinated']" +DB11386,Chlorobutanol,"Chlorobutanol, or chlorbutol, is an alcohol-based preservative with no surfactant activity5. It also elicits sedative-hypnotic and weak local anesthetic actions in addition to antibacterial and antifungal properties. Similar in nature to chloral hydrate, it is formed by the simple nucleophilic addition of chloroform and acetone.",['Q12809'],"Chlorobutanol is a detergent preservative with a broad spectrum of antimicrobial activity4.In vitro, chlorobutanol demonstrated to inhibit platelet aggregation and release via unknown mechanisms1. A study proposes that the antiplatelet effect of chlorobutanol may occur from inhibition of the arachidonic acid pathway1. It attenuated thromboxane B2 formation, elevation of cytosolic free calcium, and ATP release, and additionally exhibited a significant inhibitory activity toward several aggregation inducers in a time- and concentration-dependent manner1. Chlorobutanol may exert a direct negative inotropic effect on myocardial cells to isometric tension produced by the heart2. Chlorobutanol was shown to induce conjunctival and corneal cell toxicityin vitro: at a concentration of 0.1%, Cbl caused near depletion of the squamous layer while degeneration of corneal epithelial cells, generation of conspicuous membranous blebs, cytoplasmic swelling, and occasional breaks in the external cell membrane were observed at a concentration of 0.5%4.",CC(C)(O)C(Cl)(Cl)Cl,"As a detergent, chlorobutanol disrupts the lipid structure of the cell membrane and increases the cell permeability, leading to cell lysis. It induces conjunctival and corneal cell toxicity via causing cell retraction and cessation of normal cytokines, cell movement, and mitotic activity. It disrupts the barrier and transport properties of the corneal epithelium as well as inhibits the utilization of oxygen by the cornea. Chlorobutanol also inhibits oxygen use by the cornea, which increases susceptibility to infection.TargetActionsOrganismUPotassium voltage-gated channel subfamily H member Not AvailableHumans",[],"['Alcohols', 'Alimentary Tract and Metabolism', 'Antiemetics and Antinauseants', 'Butanols', 'Chlorohydrins', 'Compounds used in a research, industrial, or household setting', 'Fatty Alcohols', 'Lipids', 'Pharmaceutic Aids', 'Pharmaceutical Preparations', 'Preservatives, Pharmaceutical']" +DB06696,Arbekacin,An semisynthetic aminoglycoside antibiotic. Often used for treatment of multi-resistant bacterial infection such as methicillin-resistantStaphylococcus aureus(MRSA).,['P0A7S3'],"Arbekacin is an aminoglycoside. Aminoglycosides function by binding to bacterial 30S ribosomal subunits, causing t-RNA misreads, and preventing the production of proteins. Anaerobes are less susceptible to aminoglycosides because they do not spend as much energy as aerobes on taking up chemicals like aminoglycosides. Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter.",NCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)CC[C@H]2N)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O,Arbekacin irreversibly binds bacterial S and S ribosomal subunits inhibiting protein synthesis. Arbekacin binds to nucleotides of the S subunit and amino acid of protein S to interfere with the decoding site around nucleotide in the S subunit. Interference with the decoding site interferes with its interaction with the wobble base of tRNA. This hindered interaction causes mRNA to be misread and the incorrect amino acids are inserted into protein. These error filled proteins are not able to function or may even be toxic.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K),[],"['Agents that produce neuromuscular block (indirect)', 'Aminoglycoside Antibacterials', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Carbohydrates', 'Drugs that are Mainly Renally Excreted', 'Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index', 'Glycosides', 'Narrow Therapeutic Index Drugs', 'Nephrotoxic agents']" +DB04918,Ceftobiprole,Ceftobiproleis a cephalosporin antibiotic used to treat both community and hospital-acquired pneumonia caused by susceptible bacteria.,"['Q7DHH4', 'P14677', 'P0AD68']","Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistantStaphylococcus aureus.",[H][C@@]1(NC(=O)C(=N/O)\C2=NSC(N)=N2)C(=O)N2C(C(O)=O)=C(CS[C@]12[H])\C=C1/CCN(C1=O)[C@]1([H])CCNC1,"Cephalosporins, such as ceftobiprole, are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan.TargetActionsOrganismUMecANot AvailableStaphylococcus aureusUPenicillin-binding protein xNot AvailableStreptococcus pneumoniae serotype (strain ATCC BAA- / TIGR)UPeptidoglycan synthase FtsINot AvailableEscherichia coli (strain K)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Sulfur Compounds', 'Thiazines']" +DB01066,Cefditoren,Cefditorenis a broad-spectrum third-generation cephalosporin antibiotic typically used to treat bacterial infections of the skin and respiratory tract.,"['P0A3M6', 'Q8XJ01']","Cefditoren pivoxil is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren. Cefditoren is a cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens. Cefditoren is effective againstStaphylococcus aureus(methicillin-susceptible strains, including b-lactamase-producing strains), penicillin-susceptible strains ofStaphylococcus aureusandStreptococcus pneumoniae,Streptococcus pyogenes,Haemophilus influenzae(including b-lactamase-producing strains),Haemophilus parainfluenzae(including b-lactamase-producing strains),Moraxella catarrhalis(including b-lactamase-producing strains),Streptococcus agalactiae,StreptococcusGroups C and G, andStreptococcus, viridans group (penicillin-susceptible and -intermediate strains).",[H][C@]12SCC(\C=C/C3=C(C)N=CS3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O,"The bactericidal activity of cefditoren results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefditoren is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.TargetActionsOrganismAPenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein AinhibitorClostridium perfringens (strain / Type A)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Cephalosporins', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Nephrotoxic agents', 'Sulfur Compounds', 'Thiazines', 'Third-Generation Cephalosporins']" +DB00558,Zanamivir,Zanamiviris a neuraminidase inhibitor used to treat influenza A and B.,"['P06818', 'P27907', 'Q9Y3R4']","Zanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir.",[H][C@]1(OC(=C[C@H](N=C(N)N)[C@H]1NC(C)=O)C(O)=O)[C@H](O)[C@H](O)CO,"The proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. By binding and inhibiting the neuraminidase protein, the drug renders the influenza virus unable to escape its host cell and infect others.TargetActionsOrganismANeuraminidaseinhibitorInfluenza A virus (strain A/Bangkok// HN)ANeuraminidaseinhibitorInfluenza B virus (strain B/Beijing//)USialidase-inhibitorHumans",[],"['Acids, Acyclic', 'Amidines', 'Amino Sugars', 'Anti-Infective Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Carbohydrates', 'Direct Acting Antivirals', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Guanidines', 'Hydroxy Acids', 'Neuraminic Acids', 'Neuraminidase Inhibitors', 'Pyrans', 'Sialic Acids', 'Sugar Acids']" +DB06414,Etravirine,Etravirineis a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV-1 infections in combination with other antiretroviral agents.,"['P03366', 'P04585', 'Q72547']",Clinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing.,CC1=CC(=CC(C)=C1OC1=C(Br)C(N)=NC(NC2=CC=C(C=C2)C#N)=N1)C#N,"Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type (HIV-). It directly binds reverse transcriptase and consequently blocks DNA-dependent and RNA-dependent polymerase activity. Etravirine does not inhibit human DNA polymerase alpha, beta or gamma.TargetActionsOrganismUGag-Pol polyproteinNot AvailableUGag-Pol polyproteinNot AvailableUReverse transcriptase/RNaseHinhibitorHuman immunodeficiency virus ",[],"['Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Enzyme Inhibitors', 'Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor', 'Non-Nucleoside Reverse Transcriptase Inhibitors', 'Nonnucleoside Reverse Transcriptase Inhibitors', 'Nucleic Acid Synthesis Inhibitors', 'P-glycoprotein inducers', 'P-glycoprotein inhibitors', 'Reverse Transcriptase Inhibitors']" +DB01155,Gemifloxacin,Gemifloxacinis a quinolone antibacterial agent used for the treatment of acute bacterial exacerbation of chronic bronchitis and mild to moderate community-acquired pneumonia caused by susceptible bacteria.,"['P43700', 'P43702']","Gemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Gemifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.",CO\N=C1/CN(CC1CN)C1=NC2=C(C=C1F)C(=O)C(=CN2C1CC1)C(O)=O,"The bactericidal action of gemifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.TargetActionsOrganismADNA gyrase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)ADNA topoisomerase subunit AinhibitorHaemophilus influenzae (strain ATCC / DSM / KW / Rd)",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Cytochrome P-450 CYP1A2 Inhibitors', 'Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Fluoroquinolones', 'Heterocyclic Compounds, Fused-Ring', 'Moderate Risk QTc-Prolonging Agents', 'Naphthyridines', 'QTc Prolonging Agents', 'Quinolines', 'Quinolone Antimicrobial', 'Quinolones', 'Topoisomerase II Inhibitors', 'Topoisomerase Inhibitors']" +DB04835,Maraviroc,Maravirocis a CCR5 co-receptor antagonist used with other antiretroviral medications to treat CCR5-tropic HIV-1 infection.,['P51681'],Maraviroc is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5.,CC(C)C1=NN=C(C)N1[C@H]1C[C@@H]2CC[C@H](C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)C1=CC=CC=C1,"Maraviroc is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR and HIV- gp. Maraviroc selectively binds to the human chemokine receptor CCR present on the membrane of CD cells (T-cells), preventing the interaction of HIV- gp and CCR necessary for CCR-tropic HIV- to enter cells.TargetActionsOrganismAC-C chemokine receptor type antagonistinhibitorHumans",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiinfectives for Systemic Use', 'Antiviral Agents', 'Antivirals for Systemic Use', 'CCR5 Co-receptor Antagonist', 'CCR5 Receptor Antagonists', 'Cyclohexanes', 'Cycloparaffins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Direct Acting Antivirals', 'Hepatotoxic Agents', 'HIV Fusion Inhibitors', 'Triazoles', 'Viral Fusion Protein Inhibitors']" +DB06228,Rivaroxaban,Rivaroxabanis a factor Xa inhibitor used to treat deep vein thrombosis (DVT) and pulmonary embolism (PE). May also be used as thrombosis prophylaxis in specific situations.,['P00742'],"Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban.",ClC1=CC=C(S1)C(=O)NC[C@H]1CN(C(=O)O1)C1=CC=C(C=C1)N1CCOCC1=O,"Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible.TargetActionsOrganismACoagulation factor XantagonistHumans",[],"['Anticoagulants', 'Antithrombins', 'BCRP/ABCG2 Substrates', 'Blood and Blood Forming Organs', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Substrates', 'Direct factor Xa inhibitors', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Factor Xa Inhibitors', 'Hematologic Agents', 'Morpholines', 'Oxazines', 'P-glycoprotein substrates', 'Protease Inhibitors', 'Serine Protease Inhibitors', 'Sulfur Compounds', 'Thiophenes']" +DB08893,Mirabegron,Mirabegronis a beta-3 adrenergic agonist used to treat overactive bladder and neurogenic detrusor overactivity.,"['P13945', 'P08588']","Mirabegron exerts its pharmacologic effects by forcing bladder smooth muscle to relax, thereby expanding its capacity and relieving urgency. Mirabegron does not appear to adversely affect the mean maximum flow rate or mean detrusor pressure at maximum flow rate in patients with lower urinary tract symptoms and bladder outlet obstruction (BOO), but should be used with in patients with BOO due to reports of significant urinary retention. Furthermore, mirabegron increases both blood pressure and heart rate in a dose-dependent manner and should therefore be used with caution in patients with severely uncontrolled hypertension or others for whom these increases may prove dangerous.6",NC1=NC(CC(=O)NC2=CC=C(CCNC[C@H](O)C3=CC=CC=C3)C=C2)=CS1,"Mirabegron is a potent and selective agonist of beta- adrenergic receptors. The activation of beta- receptors relaxes detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle, which increases the bladder's storage capacity thereby alleviating feelings of urgency and frequency.TargetActionsOrganismABeta- adrenergic receptoragonistHumansUBeta- adrenergic receptoragonistHumans",[],"['Adrenergic Agents', 'Adrenergic Agonists', 'Adrenergic beta-3 Receptor Agonists', 'Adrenergic beta-Agonists', 'Agents producing tachycardia', 'Agents that produce hypertension', 'Amides', 'Amines', 'Anilides', 'Aniline Compounds', 'Cholinesterase substrates', 'Cytochrome P-450 CYP2D6 Inhibitors', 'Cytochrome P-450 CYP2D6 Inhibitors (moderate)', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs for Urinary Frequency and Incontinence', 'Drugs that are Mainly Renally Excreted', 'Genito Urinary System and Sex Hormones', 'Genitourinary Agents', 'OCT1 substrates', 'OCT2 Substrates', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Selective Beta 3-adrenergic Agonists', 'Sulfur Compounds', 'UGT1A3 substrates', 'UGT2B7 substrates', 'Urological Agents', 'Urologicals']" +DB00736,Esomeprazole,"Esomeprazoleis a proton pump inhibitor used to treat GERD, reduce the risk of NSAID associated gastric ulcers, eradicate H. pylori, and to treat conditions causing gastric acid hypersecretion.","['P20648', 'O94760']","Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, andH. pylorieradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.Esomeprazole is the s-isomer ofOmeprazole, which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent asOmeprazole, without any significant differences between the two compoundsin vitro.PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes.3,4Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinalC. difficile), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.5",COC1=CC2=C(NC(=N2)[S@@](=O)CC2=NC=C(C)C(OC)=C2C)C=C1,"Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect that persists longer than hours.LabelTargetActionsOrganismAPotassium-transporting ATPase alpha chain inhibitorHumansUN(G),N(G)-dimethylarginine dimethylaminohydrolase Not AvailableHumans",[],"['2-Pyridinylmethylsulfinylbenzimidazoles', 'Acid Reducers', 'Alimentary Tract and Metabolism', 'Anti-Ulcer Agents', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Benzimidazoles', 'Cytochrome P-450 CYP2C19 Inhibitors', 'Cytochrome P-450 CYP2C19 Inhibitors (weak)', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Drugs causing inadvertant photosensitivity', 'Drugs for Acid Related Disorders', 'Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)', 'Enzyme Inhibitors', 'Gastric Acid Lowering Agents', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Musculo-Skeletal System', 'OAT3/SLC22A8 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Photosensitizing Agents', 'Propionates', 'Proton Pump Inhibitors', 'Proton-pump Inhibitors', 'Pyridines', 'Sulfoxides', 'Sulfur Compounds']" +DB00634,Sulfacetamide,Sulfacetamideis a sulfonamide used to treat inflammatory ocular conditions and acne vulgaris.,"['P0AC13', 'P0C002', 'P53848']","Sulfacetamide is a sulfonamide antibiotic with bacteriostatic actions and broad-spectrum activity against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors ofp-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.",CC(=O)NS(=O)(=O)C1=CC=C(N)C=C1,"Sulfacetamide is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), an essential component for bacterial growth (according to the Woods-Fildes theory). The inhibited reaction is necessary in these organisms for the synthesis of folic acid.TargetActionsOrganismADihydropteroate synthaseinhibitorEscherichia coli (strain K)ADihydropteroate synthase type-inhibitorEscherichia coliAFolic acid synthesis protein FOLinhibitorBaker's yeast",[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Anti-Infective Agents, Urinary', 'Antiinfectives for Treatment of Acne', 'Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Ophthalmologicals', 'Sensory Organs', 'Sulfanilamides', 'Sulfonamide Antibacterial', 'Sulfonamides', 'Sulfones', 'Sulfur Compounds']" +DB06203,Alogliptin,Alogliptinis a dipeptidyl peptidase-4 (DPP-4) inhibitor used to treat hyperglycemia in patients with type 2 diabetes mellitus.,['P27487'],Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.,CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O,"Alogliptin inhibits dipeptidyl peptidase (DPP-), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide ( GLP-). The inhibition of DPP- increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP- stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP- has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.TargetActionsOrganismADipeptidyl peptidase inhibitorHumans",[],"['Agents causing angioedema', 'Alimentary Tract and Metabolism', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'DPP-IV Inhibitors', 'Drugs that are Mainly Renally Excreted', 'Drugs Used in Diabetes', 'Enzyme Inhibitors', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Incretins', 'Oral Hypoglycemics', 'Protease Inhibitors', 'Pyrimidines', 'Pyrimidinones']" +DB06211,Doripenem,Doripenemis an antibiotic of the penem class used to treat complicated intra-abdominal and urinary tract infections.,"['P02918', 'P02919', 'P0AD65', 'Q51504', 'P72355']","Similar to other beta-lactam antimicrobial agents, the time that unbound plasma concentration of doripenem exceeds the MIC (T>MIC) of the infecting organism has been shown to best correlate with efficacy in animal models of infection.",[H][C@]12[C@@H](C)C(S[C@@H]3CN[C@H](CNS(N)(=O)=O)C3)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O,"Doripenem is a broad-spectrum carbapenem antibiotic with activity against many gram-positive and gram-negative aerobic bacteria, as well as a variety of anaerobes. Like other beta-lactam antibiotics, doripenem's bactericidal mechanism of action is mostly due to cell death after inhibition of bacterial enzymes called penicillin-bindng proteins (PBPs), which are responsible for peptidoglycan cross-linking during the synthesis of the bacterial cell wall. Carbapenems mainly have high affinity for PBPs a, b, and . Inhibition of each PBP usually results in a different inactivating mechanism. Inhibition of PBPs a and b results in fast bacterial killing through the formation of spheroplasts, inhibition of PBP results in rod-shaped bacteria to become spherical, and inhibition of PBP results in filamentous-shaped organisms. The PBPs preferentially bound by different carbapenems depend on the organism. In E.coli and P.aeruginosa, doripenem binds to PBP +, which is involved in the maintenance of cell shape, as well as to PBPs and . Doripenem has a -beta-methyl side chain, which allows it to be relatively resistant to dehydropeptidase, as well as a trans-alpha--hydroxyethyl group at position which provides beta-lactamase resistance. Like other carbapenems, doripenem is different from most beta-lactams due to its stability against hydrolysis by most beta-lactamases, including penicillinases, cephalosporinases, ESBL, and Amp-C producing enterobacteriaceae.TargetActionsOrganismAPenicillin-binding protein AantagonistinhibitorEscherichia coli (strain K)APenicillin-binding protein BantagonistinhibitorEscherichia coli (strain K)APenicillin-binding protein antagonistinhibitorEscherichia coli (strain K)APenicillin-binding protein antagonistinhibitorPseudomonas aeruginosaAPenicillin-binding protein antagonistinhibitorStaphylococcus aureus",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'beta-Lactams', 'Carbapenems', 'Drugs that are Mainly Renally Excreted', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'OAT3/SLC22A8 Substrates', 'Penem Antibacterial', 'Sulfur Compounds']" +DB00754,Ethotoin,Ethotoinis a hydantoin antiepileptic used to control tonic-clonic and complex partial seizures.,"['Q14524', 'O75469']","Ethotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges.",CCN1C(=O)NC(C1=O)C1=CC=CC=C1,"The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumansUNuclear receptor subfamily group I member activatorHumans",[],"['Anti-epileptic Agent', 'Anticonvulsants', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 Enzyme Inducers', 'Decreased Central Nervous System Disorganized Electrical Activity', 'Hydantoins', 'Imidazoles', 'Imidazolidines', 'Membrane Transport Modulators', 'Nervous System', 'Sodium Channel Blockers', 'Thyroxine-binding globulin substrates', 'Voltage-Gated Sodium Channel Blockers']" +DB13155,Esculin,"Esculin is found in barley. Vitamin C2 is generally considered a bioflavanoid, related to vitamin P esculin is a glucoside that naturally occurs in the horse chestnut (Aesculus hippocastanum), California Buckeye (Aesculus californica) and in daphnin (the dark green resin of Daphne mezereum). Esculin belongs to the family of Glycosyl Compounds. These are carbohydrate derivatives in which a sugar group is bonded through its anmoeric carbonA to another group via a C-, S-,N-,O-, or Se- glycosidic bond.","['P10275', 'P10275']",Topically applied Esculine increases the “capillary density” (the number of capillaries open to flow per surface unit) and improves the morphological aspect of the smallest blood vessels.,OC[C@H]1O[C@@H](OC2=C(O)C=C3OC(=O)C=CC3=C2)[C@H](O)[C@@H](O)[C@@H]1O,"The main activities of Esculine focus on capillary protection, as it improves capillary permeability and fragility. It is reported to inhibit catabolic enzymes such as hyaluronidase and collagenase, thus preserving the integrity of the perivascular connective tissue. Esculine also showed good antioxidant properties, protecting triglycerides against auto-oxidation at high temperatures . The antioxidant property might as well explain some of the anti-inflammatory activity of the product, making it a suitable product for after sun treatments, for example.TargetActionsOrganismUAndrogen receptoragonistHumans",[],"['Benzopyrans', 'Carbohydrates', 'Coumarins', 'Glucosides', 'Glycosides', 'Heterocyclic Compounds, Fused-Ring', 'Pyrans']" +DB13729,Camostat,Camostatis a serine protease indicated in Japan to treat chronic pancreatitis.,"['P07477', 'O15393', 'Q9Y5Y6', 'P06307']","Camostat mesylate is a protease inhibitor used to treat chronic pancreatitis.3The duration of action is not long, as it is typically given in 3 divided doses daily.9Patients should be counselled regarding the risk of anaphylaxis, thrombocytopenia, hepatic dysfunction, and hyperkalemia.9",CN(C)C(=O)COC(=O)CC1=CC=C(OC(=O)C2=CC=C(NC(N)=N)C=C2)C=C1,"In rats, oral camostat mesylate may increase pancreatic secretions and hypertrophy by increasing cholecystokinin release.Administration in rats has also lead to lower levels of IL-beta, IL-, TNF-alpha, TGF-beta, and PSC.Similar activity is seem after administration in humans, leading to reduced pain and inflammation as well as improve the function of the pancrease in chronic pancreatitis.In the case of SARS-CoV-, camostat mesylate inhibits the action of the serine protease TMPRSS, preventing the priming of the viral spike protein for attachment to ACE, and entry into the cell.TargetActionsOrganismUTrypsin-inhibitorHumansUTransmembrane protease serine inhibitorHumansUSuppressor of tumorigenicity proteininhibitorHumansUCholecystokinininhibitorHumans",[],"['Amidines', 'Antifibrinolytic Agents', 'Blood and Blood Forming Organs', 'Enzyme Inhibitors', 'Guanidines', 'Hemostatics', 'Protease Inhibitors', 'Proteinase Inhibitors', 'Serine Protease Inhibitors', 'Trypsin Inhibitors']" +DB09204,Arotinolol,"Arotinolol is an alpha- and beta-receptor blocker developed in Japan. It is a thiopropanolamine with a tertiary butyl moiety. It has been studied for its potential to be an antihypertensive therapy.6Artinolol is being developed by Sumitomo Pharmaceutical Co., Ltd. and it is currently under clinical trials.10","['P08588', 'P07550', 'P35348', 'P35368', 'P25100']","Preclinical studies showed a lack of intrinsic sympathomimetic activities or membrane-establishing properties. It is confirmed that arotinolol presents vasorelaxant activity. This characteristic is also proved to be mainly mediated by its α1-blocking property. In preclinical hypertension trials, there is a specific acute bradycardiac and antihypertensive activity with a pronounced reduction in heart rate. Some reports indicate a delayed development of hypertension when arotinolol is administered daily. Arotinolol has a dose-dependent decrease in cardiac contractility and coronary blood flow as well as an increase in total peripheral resistance. The effects of arotinolol have been confirmed in clinical trials where this drug was able to decrease cardiac index and thus, blood pressure.6",CC(C)(C)NCC(O)CSC1=NC(=CS1)C1=CC=C(S1)C(N)=O,"Arotinolol binds to the β-, β- and α- adrenergic receptor sites with a very high affinity. Radioligand studies have shown that arotinolol presents a higher affinity to the β-receptor compared to the α-receptor. The elucidated mechanism of action seems to be the result of a reduction in the cardiac output via the β-blockade and an additional inhibition of the counter-regulatory increase in peripheral resistance mediated by the α-blockade.TargetActionsOrganismABeta- adrenergic receptorantagonistHumansABeta- adrenergic receptorantagonistHumansAAlpha- adrenergic receptorsantagonistHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Adrenergic beta-Antagonists', 'Agents causing hyperkalemia', 'Alcohols', 'Amines', 'Amino Alcohols', 'Bradycardia-Causing Agents', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Propanols']" +DB01158,Bretylium,"Bretyliumis a norepinephrine release inhibitor used for the prophylaxis and therapy of ventricular fibrillation, as well as the treatment of life-threatening ventricular arrhythmias.",['P05023'],Bretylium is a bromobenzyl quaternary ammonium compound which selectively accumulates in sympathetic ganglia and their postganglionic adrenergic neurons where it inhibits norepinephrine release by depressing adrenergic nerve terminal excitability. Bretylium also suppresses ventricular fibrillation and ventricular arrhythmias.,CC[N+](C)(C)CC1=CC=CC=C1Br,"Bretylium inhibits norepinephrine release by depressing adrenergic nerve terminal excitability. The mechanisms of the antifibrillatory and antiarrhythmic actions of bretylium are not established. In efforts to define these mechanisms, the following electrophysiologic actions of bretylium have been demonstrated in animal experiments: increase in ventricular fibrillation threshold, increase in action potential duration and effective refractory period without changes in heart rate, little effect on the rate of rise or amplitude of the cardiac action potential (Phase ) or in resting membrane potential (Phase ) in normal myocardium, decrease in the disparity in action potential duration between normal and infarcted regions, and increase in impulse formation and spontaneous firing rate of pacemaker tissue as well as increase ventricular conduction velocity.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-inhibitorHumans",[],"['Adrenergic Agents', 'Adrenergic Antagonists', 'Amines', 'Antiarrhythmic agents', 'Antiarrhythmics, Class III', 'Antihypertensive Agents', 'Benzylammonium Compounds', 'Bradycardia-Causing Agents', 'Bretylium Compounds', 'Cardiac Therapy', 'Cardiovascular Agents', 'Hypotensive Agents', 'Neurotransmitter Agents', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents', 'Quaternary Ammonium Compounds']" +DB01125,Anisindione,"Anisindione is a synthetic anticoagulant and an indanedione derivative. Its anticoagulant action is mediated through the inhibition of the vitamin K-mediated gamma-carboxylation of precursor proteins that are critical in forming the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, in the liver.",['P38435'],"Anisindione is a synthetic anticoagulant and an indanedione derivative. It is prescribed only if you cannot take coumarin-type anticoagulants such as coumadin as anisindione is a powerful drug with serious potential side effects. Anticoagulants decrease the clotting ability of the blood and therefore help to prevent harmful clots from forming in the blood vessels. These medicines are sometimes called blood thinners, although they do not actually thin the blood. They also will not dissolve clots that already have formed, but they may prevent the clots from becoming larger and causing more serious problems.",COC1=CC=C(C=C1)C1C(=O)C2=CC=CC=C2C1=O,"Like phenindione, to which it is related chemically, anisindione exercises its therapeutic action by reducing the prothrombin activity of the blood. By inhibiting the vitamin K–mediated gamma-carboxylation of precursor proteins, the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S is prevented. Anisindione has no direct thrombolytic effect and does not reverse ischemic tissue damage, although it may limit extension of existing thrombi and prevent secondary thromboembolic complications.TargetActionsOrganismAVitamin K-dependent gamma-carboxylaseinhibitorHumans",[],"['Indans', 'Indenes']" +DB00154,Dihomo-gamma-linolenic acid,"A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.","['P35354', 'P23219']",Dihomo gamma-linolenic acid or DHLA is an n-6 (omega-6) polyunsaturated fatty acid. It is comprised of 20 carbon atoms and three double bonds. DHLA is a byproduct of the 18 carbon gamma-linolenic acid (GLA). DHLA is then converted into prostaglandin E1 (PGE1). PGE1 inhibits platelet aggregation and also exerts a vasodilatory effect.,CCCCC\C=C/C\C=C/C\C=C/CCCCCCC(O)=O,"DHLA (or DGLA) is a precursor in the synthesis of prostaglandin E (PGE) as well as the series- prostaglandins. It also serves as a precursor in the synthesis of eicosapentaenoic acid (EPA). EPA is a precursor of the series- prostaglandins, the series- leukotrienes and the series- thromboxanes. These eicosanoids have anti-thrombogenic, anti-inflammatory and anti-atherogenic properties. PGE inhibits platelet aggregation and has a vasodilation action. DHLA has also been shown to reduce the production/activity of tumor necrosis factor alpha.TargetActionsOrganismAProstaglandin G/H synthase Not AvailableHumansAProstaglandin G/H synthase inhibitorHumans",[],"['Dietary Supplements', 'Eicosanoids', 'Fatty Acids', 'Fatty Acids, Unsaturated', 'Lipids', 'Supplements']" +DB11085,Resorcinol,"Resorcinol is a 1,3-isomer (or meta-isomer) of benzenediol with the formula C6H4(OH)2. It is used as an antiseptic and disinfectant in topical pharmaceutical products in the treatment of skin disorders and infections such as acne, seborrheic dermatitis, eczema, psoriasis, corns, calluses, and warts. It exerts a keratolytic activity. Resorcinol works by helping to remove hard, scaly, or roughened skin.",['P07202'],"In vitro and in vivo studies have demonstrated that resorcinol can inhibit peroxidases in the thyroid and subsequently block the synthesis of thyroid hormones and cause goiter6,4. Resorcinol interferes with the iodination of tyrosine and the oxidation of iodide6,4. In an in vitro study involving lactoperoxidase (LPO) and thyroid peroxidase (TPO), it was shown that the mechanism of these two enzymes can become irreversibly inhibited by way of a suicide inactivation by resorcinol6,4.It is believed that the Fe3+ of the porphyrin residue of the peroxidase to is oxidised to Fe4+ by hydrogen peroxide with the transfer of an oxygen radical6,4. In LPO and TPO, the resulting π-cation radical of the porphyrin can isomerize to a radical cation with the radical in an aromatic side chain of the enzyme6,4. The latter radical can bind, in a pH-dependent reaction, covalently and irreversibly to the resorcinol radical formed during regular oxidation of resorcinol and this reduces the activity of the enzyme greatly6,4. While the inactivation of the enzyme and the binding of resorcinol to the enzyme may be largely increased by the presence of 0.1 nM iodide, increasing the iodide concentration to 5 mM reduced the resorcinol binding to the enzyme by one quarter but increased the enzyme activity, determined as the rate of iodination of tyrosine, more than proportionally from 6.2% to 44.7%6,4. Nevertheless, the role played by iodide ions in the irreversible inactivation of the enzymes is not yet fully elucidated6,4.Ultimately, such in vitro and in vivo data propose that the anti-thyroidal activity of resorcinol is caused by inhibition of thyroid peroxidase enzymes, resulting in decreased thyroid hormone production and increased proliferation due to an increase in the secretion of TSH (thyroid stimulating hormone)6,4. The iodination process is catalyzed by a haem-containing enzyme, and resorcinol is known to form covalent bonds with haem6,4.Despite the legitimacy of this pharmacodynamic profile in resorcinol, the therapeutic uses for which it may be formally indicated for at this time do not actually rely upon any of these mechanisms or dynamics, which are primarily elicited only upon systemic exposure to resorcinol or particularly high overdosage of the agent. This is especially true, considering resorcinol is most commonly available as topical applications to the public.",OC1=CC(O)=CC=C1,"Data regarding the specific mechanisms of action of resorcinol does not appear to be readily accessible in the literature. Nevertheless, the effectiveness of the agent in treating various topical, dermatological conditions by eliciting antibacterial and keratolytic actions appears to stem from resorcinol's propensity for protein precipitation,. In particular, it appears that resorcinol indicated for treating acne, dermatitis, or eczema in various skin care topical applications and peels revolves around the compound's ability to precipitate cutaneous proteins from the treated skin.TargetActionsOrganismUThyroid peroxidaseNot AvailableHumans",[],"['Anti-Acne Preparations', 'Anti-Acne Preparations for Topical Use', 'Anti-Infective Agents', 'Anti-Infective Agents, Local', 'Benzene Derivatives', 'Dermatologicals', 'Drugs that are Mainly Renally Excreted', 'Ophthalmologicals', 'Phenols', 'Root Canal Filling Materials', 'Sensory Organs']" +DB05154,Pretomanid,Pretomanidis part of a three-drug regimen used for the treatment of extensively drug-resistant and multidrug-resistant pulmonary tuberculosis.,"['P95029', 'P9WJY5', 'P9WIP7', 'A0A0T9AZ62', 'A0A1K3GRG2', 'A0A045KKX4', 'A0A045ISQ8', 'P9WGR1']","Pretomanid kills the actively replicating bacteria causing tuberculosis, known as Mycobacterium tuberculosis, and shortens the duration of treatment in patients who suffer from resistant forms of pulmonary TB by killing dormant bacteria.4,5,7,10In rodent models of tuberculosis infection, pretomanid administered in a regimen with bedaquiline and linezolid caused a significant reduction in pulmonary bacterial cell counts. A decrease in the frequency of TB relapses at 2 and 3 months after treatment was observed after the administration of this regimen, when compared to the administration of a 2-drug regimen.10Successful outcomes have been recorded for patients with XDR and MDR following a clinical trial of the pretomanid regimen, demonstrating a 90% cure rate after 6 months.14A note on cardiac QT prolongation, hepatotoxicity, and myelosuppressionThis drug has the propensity to caused cardiac QT interval prolongation and significant hepatotoxicity, as well as myelosuppression. Caution must be observed during the administration of this drug.10,12",[O-][N+](=O)C1=CN2C[C@@H](COC2=N1)OCC1=CC=C(OC(F)(F)F)C=C1,"Pretomanid is a prodrug which is metabolically activated by a nitroreductase enzyme, known as Ddn, producing various active metabolites that are responsible for its other therapeutic actions, particularly the induction of nitric oxide. The nitroreductase enzyme which activates pretomanid is deazaflavin dependent and relies on reduced cofactor F. Reduction of F occurs via the enzyme glucose--phosphate dehydrogenase.Reduction of pretomanid's imidazole ring at the C- position causes the formation of the metabolites, which include a des-nitro derivative. The formation of this derivative leads to increased levels of nitric oxide, leading to bactericidal activities under anaerobic conditions via its action as a bacterial respiratory poison.,Bactericidal activity against anaerobes is reported to be associated with a shortened duration of antibiotic treatment.Pretomanid exerts aerobic bactericidal effects through its inhibitory actions on bacterial cell wall mycolic acid biosynthesis. This allows for the killing of actively replicating Mycobacterium tuberculosis bacteria, resulting in the treatment of active tuberculosis infection.,The molecular mechanism of the above bactericidal effects is poorly understood at this time, but may involve effects exerted on various genes that affect the cell wall, including the fasI and fasII as well as the efpA and iniBAC operons. Other possible targets include the genes of the cyd operon. The clinical effects of the above target relations are unknown at this time.TargetActionsOrganismUFatty acid synthetaseother/unknownMycobacterium tuberculosis (strain ATCC / HRv)UUncharacterized MFS-type transporter EfpAother/unknownMycobacterium tuberculosis (strain ATCC / HRv)UNucleoid-associated protein Lsrother/unknownMycobacterium tuberculosis (strain ATCC / HRv)UCyd operon, Mycobacterium tuberculosisother/unknownMycobacterium tuberculosisUEnoyl-[acyl-carrier-protein] reductase [NADH]other/unknownMycobacterium tuberculosis",[],"['Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Drugs for Treatment of Tuberculosis', 'Imidazoles', 'Nitro Compounds', 'OAT3/SLC22A8 Inhibitors']" +DB11921,Deflazacort,Deflazacortis a corticosteroid used to treat Duchenne muscular dystrophy.,['P04150'],"Deflazacort exerts anti-inflammatory activity in DMD, likely improving various symptoms, including muscle weakness and cardiorespiratory symptoms in addition to delaying their onset.6This allows for an increased quality of life and prevents the necessity for surgical procedures, such as those for scoliosis, which is associated with DMD. Studies showed significant preservation of muscle mass in patients generally treated with 0.9 mg/kg/day of deflazacort compared to a control group. The following findings are based on clinical studies using deflazacort on a long term basis6,8:Effects on muscle strengthAt age 16, individuals treated with long-term deflazacort had 63 ± 4% score in muscle strength compared to a mean muscle strength score of 31 ± 3% for control patients6. Significant improvements in climbing stairs and rising from a supine position were also seen in patients taking deflazacort.6Effects on ambulationAmbulation was significantly higher by 12 years of age and 18 years of age in patients taking deflazacort when compared with the control group. The control group showed a mean loss of ambulation of 2 years sooner than with deflazacort treatment.8Effects on cardiac functionMean left ventricular ejection fraction (a measure of cardiac function) was higher in patients treated with deflazacort over the long term. Preservation of cardiac function was demonstrated by a mean difference in ejection fraction of about 7%, favoring study groups taking deflazacort over control groups.8Effects on spinal alignmentChildren treated with deflazacort also significantly lowered the rate and severity of scoliosis and eliminated the need for scoliosis surgery after long-term treatment.6,8",[H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@]([H])(O)C[C@]3(C)[C@@]1(N=C(C)O2)C(=O)COC(C)=O,"Deflazacort is a corticosteroid prodrug with an active metabolite, -deflazacort, which binds to the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects on the body.,,The exact mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown but likely occurs via its anti-inflammatory activities.LabelTargetActionsOrganismUGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids for Systemic Use', 'Corticosteroids for Systemic Use, Plain', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Inducers', 'Cytochrome P-450 CYP3A5 Inducers (strength unknown)', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Fused-Ring Compounds', 'Glucocorticoids', 'Hyperglycemia-Associated Agents', 'Immunosuppressive Agents', 'Steroids', 'Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins']" +DB01078,Deslanoside,Deacetyllanatoside C. A cardiotonic glycoside from the leaves of Digitalis lanata.,['P05023'],"Deslanoside is a cardiac glycoside used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.",C[C@H]1O[C@H](C[C@H](O)[C@@H]1O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)[C@@H](C)O2)[C@@H](C)O1)O[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2C[C@@H](O)[C@]2(C)[C@H](CC[C@]32O)C2=CC(=O)OC2)C1,"Deslanoside inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Deslanoside also acts on the electrical activity of the heart, increasing the slope of phase depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.TargetActionsOrganismASodium/potassium-transporting ATPase subunit alpha-inhibitorHumans",[],"['Antiarrhythmic agents', 'Carbohydrates', 'Cardanolides', 'Cardenolides', 'Cardiac Glycosides', 'Cardiac Therapy', 'Cardiotonic Agents', 'Cardiovascular Agents', 'Compounds used in a research, industrial, or household setting', 'Digitalis Glycosides', 'Enzyme Inhibitors', 'Fused-Ring Compounds', 'Glycosides', 'Lanatosides', 'Protective Agents', 'Steroids']" +DB12874,Quizartinib,Quizartinibis a FLT3 inhibitor used in combination with cytarabine and anthracycline to treat acute myeloid leukemia with FLT3 internal tandem duplication,['P36888'],"Quizartinib showed antitumor activity in a mouse model of FLT3-ITD-dependent leukemia. In vitro, studies have shown that quizartinib is a predominant inhibitor of the slow delayed rectifier potassium current, IKs.4In AML patients receiving quizartinib at a dose of 90 mg/day for females and 135 mg/day for males on a 28-day schedule, the median levels of phospho-FLT3 (pFLT3) and total FLT3 (tFLT3) decreased from 3312 RLU or 5639 RLU respectively at day 1 to 1235 RLU and 142 RLU respectively at day 8. Additionally, pFLT3 levels are statistically significantly higher (p < 0.0001, Mann Whitney test) for the ITD+ subjects on day 1; however, pFLT3 levels was reduced to a similar level in patients with or without the ITD mutation.5The exposure-response analysis predicted a concentration-dependent QTcF interval median prolongation of 18 and 24 ms [upper bound of 2-sided 90% confidence interval (CI): 21 and 27 ms] at the median steady-state Cmax of quizartinib at the 26.5 mg and 53 mg dose level during maintenance therapy.4",CC(C)(C)C1=CC(NC(=O)NC2=CC=C(C=C2)C2=CN3C(SC4=C3C=CC(OCCN3CCOCC3)=C4)=N2)=NO1,"Quizartinib is a small molecule inhibitor of the receptor tyrosine kinase FLT. Quizartinib and its major active metabolite AC bind to the adenosine triphosphate (ATP) binding domain of FLT with comparable affinity, and both had -fold lower affinity towards FLT-ITD mutation compared to FLT in a binding assay. Quizartinib and AC inhibited FLT kinase activity, preventing autophosphorylation of the receptor, thereby inhibiting downstream FLT receptor signaling and blocking FLT-ITD-dependent cell proliferation.TargetActionsOrganismAReceptor-type tyrosine-protein kinase FLTinhibitorHumans",[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inhibitors', 'Benzene Derivatives', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 CYP3A7 Substrates', 'Cytochrome P-450 Substrates', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'Protein Kinase Inhibitors', 'Sulfur Compounds', 'Thiazoles', 'Tyrosine Kinase Inhibitors', 'UGT1A1 Inhibitors']" +DB04886,Calanolide A,"Calanolide A is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) derived from a plant found in the Malaysian rain forest. A related compound, calanolide B, also has anti-HIV activity. Both drugs are being developed by Sarawak Pharmaceuticals. A preliminary dosing study among HIV-infected individuals showed a significant antiviral effect compared with placebo.",['P03369'],"Calanolide A is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) derived from a plant found in the Malaysian rain forest. A related compound, calanolide B, also has anti-HIV activity. Both drugs are being developed by Sarawak Pharmaceuticals. The drug is metabolised by cytochrome P450 CYP3A, and its developers have suggested that drug levels may be enhanced if co-administered with ritonavir (Norvir). The drug is active in the test tube against HIV with the two most common NNRTI-related mutations, K103N and Y181C, and selects for a mutation which does not cause cross-resistance with any other NNRTIs currently under investigation. A substitution at codon Y188H of reverse transcriptase has been associated with 30-fold resistance to calanolide A in vitro (Quan 1999). The compound is essentially inactive against strains of the less common HIV type 2.",CCCC1=CC(=O)OC2=C1C1=C(C=CC(C)(C)O1)C1=C2[C@@H](O)[C@H](C)[C@@H](C)O1,"Viral life-cycle studies indicate that calanolide A acts early in the infection process, similar to the known HIV reverse transcriptase (RT) inhibitor ', '-dideoxycytidine. In enzyme inhibition assays, calanolide A potently and selectively inhibits recombinant HIV type RT but not cellular DNA polymerases or HIV type RT within the concentration range tested.TargetActionsOrganismUGag-Pol polyproteinNot AvailableHIV-",[],"['Anti-HIV Agents', 'Anti-Infective Agents', 'Anti-Retroviral Agents', 'Antiviral Agents', 'Benzopyrans', 'Calophyllum', 'Coumarins', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Heterocyclic Compounds, Fused-Ring', 'Plant Extracts', 'Pyrans']" +DB11614,Rupatadine,Rupatadineis a selective histamine H1 receptor antagonist and platelet activating factor (PAF) antagonist used to treat allergic rhinitis.,"['P25105', 'P35367']","Rupatadine is an anti allergenic and acts to reduce allergic symptoms like urticaria, rhinorrhea, sneezing and itchingLabel.",CC1=CC(CN2CCC(CC2)=C2C3=CC=C(Cl)C=C3CCC3=C2N=CC=C3)=CN=C1,"Rupatadine is a dual histamine H receptor and platelet activating (PAF) receptor antagonistLabel. During allergic response mast cells undergo degranulation, releasing histamine and other substances. Histamine acts on H receptors to produce symptoms of nasal blockage, rhinorhea, itching, and swelling. PAF is produced from phospholipids cleaved by phospholipase A. It acts to produce vascular leakage which contributes to rhinorhea and nasal blockage. By blocking both the H receptor and PAF receptor, rupatidine prevents these mediators from exerting their effects and so reduces the severity of allergic symptoms.TargetActionsOrganismAPlatelet-activating factor receptorantagonistHumansAHistamine H receptorantagonistHumans",[],"['Antihistamines for Systemic Use', 'Benzocycloheptenes', 'Cytochrome P-450 CYP2C19 Substrates', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2D6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Dibenzocycloheptenes', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Piperidines', 'Platelet Activating Factor, antagonists & inhibitors', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']" +DB00256,Lymecycline,Lymecyclineis a tetracycline antibiotic used for the treatment of acne vulgaris and other susceptible infections.,['P0A7V8'],"Lymecycline, like other tetracyclines, exerts bacteriostatic actions on intracellular and extracellular bacteria, treating susceptible bacterial infections.9It has been shown to be safe and effective in the treatment of moderate to severe acne.1It is important to note that like other tetracyclines, lymecycline may cause esophageal irritation and ulceration, which can be prevented by drinking adequate fluids during administration. It also has the potential to cause photosensitivity. Lymecycline can lead to renal tubular acidosis or hepatic toxicity. It is not recommended to administer this drug in patients with renal disease or severe hepatic disease.8,9",[H][C@@]12C[C@@]3([H])C(C(=O)C4=C(O)C=CC=C4[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(=O)NCNCCCC[C@H](N)C(O)=O)=C(O)[C@H]2N(C)C,"Normally, the ribosome synthesizes proteins through the binding of aminoacyl-tRNA to the mRNA-ribosome complex. Lymecycline binds to the S ribosomal subunit, preventing amino-acyl tRNA from binding to the A site of the ribosome, which prevents the elongation of polypeptide chains.,,This results in bacteriostatic actions, treating various infections.TargetActionsOrganismAS ribosomal protein SinhibitorEscherichia coli (strain K)",[],"['Agents that produce neuromuscular block (indirect)', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Naphthacenes', 'Tetracyclines']" +DB01163,Amdinocillin,Amidinopenicillanic acid derivative with broad spectrum antibacterial action. It is poorly absorbed if given orally and is used in urinary infections and typhus. Amdinocillin is not available in the United States.,"['Q8DNB6', 'P0AD65', 'Q75Y35', 'Q8DR59', 'P0A3M6', 'Q7CRA4']","Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Co-administration of probenecid results in markedly elevated plasma levels of amdinocillin and delays its excretion.",[H]C(=N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@]12[H])N1CCCCCC1,"Amdinocillin is a stong and specific antagonist of Penicillin Binding Protein- (PBP ). It is active against gram negative bacteria, preventing cell wall synthesis by inhibiting the activity of PBP. PBP is a peptidoglycan elongation initiating enzyme. Peptidoglycan is a polymer of sugars and amino acids that is the main component of bacterial cell walls.TargetActionsOrganismAPenicillin-binding protein ainhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein inhibitorEscherichia coli (strain K)APenicillin-binding protein inhibitorStreptococcus pneumoniaeAPenicillin-binding protein AinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein BinhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)APenicillin-binding protein binhibitorStreptococcus pneumoniae (strain ATCC BAA- / R)",[],"['Amides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Anti-Infective Agents, Urinary', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Beta-Lactam Antibacterials', 'beta-Lactams', 'Heterocyclic Compounds, Fused-Ring', 'Lactams', 'Penicillins', 'Penicillins With Extended Spectrum', 'Sulfur Compounds']" +DB00963,Bromfenac,Bromfenacis an NSAID used to treat postoperative pain and inflammation of the eye.,"['P35354', 'P23219']","Bromfenac ophthalmic solution is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use.",NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1,"The mechanism of its action is thought to be due to its ability to block prostaglandin synthesis by inhibiting cyclooxygenase and . Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansUProstaglandin G/H synthase inhibitorHumans",[],"['Agents causing hyperkalemia', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antirheumatic Agents', 'Benzene Derivatives', 'Central Nervous System Agents', 'Cyclooxygenase Inhibitors', 'Hydrocarbons, Brominated', 'Hydrocarbons, Halogenated', 'Ketones', 'Nephrotoxic agents', 'Ophthalmologicals', 'Peripheral Nervous System Agents', 'Selective Cyclooxygenase 2 Inhibitors (NSAIDs)', 'Sensory Organs', 'Sensory System Agents']" +DB06751,Drotaverine,Drotaverineis a phosphodiesterase-4 inhibitor used to alleviate gastrointestinal and genitourinary smooth muscle spasms.,"['P27815', 'Q13936', 'Q01668', 'O60840', 'Q13698', 'Q02641', 'Q08289', 'P54284', 'O00305', 'O00555']","Drotaverine is an e spasmolytic agent with a relaxing effect on smooth muscles. It works to relieve visceral spasms and improve cervical dilation.In vitro, drotaverine mediated cytostatic effects on several human tumor cell lines and nonmalignant mouse fibroblasts.5Drotaverine may have minor allosteric calcium channel blocking properties:in vitro, drotaverine behaves like voltage-dependent L-type calcium channel blockers.8",CCOC1=C(OCC)C=C(\C=C2/NCCC3=CC(OCC)=C(OCC)C=C23)C=C1,"Drotaverine is a selective inhibitor of phosphodiesterase (PDE), which is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP). Inhibition of PDE leads to elevated levels of cAMP, leading to smooth muscle relaxation. Recent research showed that low levels of cAMP have been associated with brain tumorigenesis, leading to the investigation of PDE inhibitors as potential anticancer agents.TargetActionsOrganismAcAMP-specific ','-cyclic phosphodiesterase AinhibitorHumansUVoltage-dependent L-type calcium channelinhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Alkaloids', 'Analgesics', 'Autonomic Agents', 'Benzylisoquinolines', 'Cardiovascular Agents', 'Central Nervous System Agents', 'Drugs for Functional Gastrointestinal Disorders', 'Heterocyclic Compounds, Fused-Ring', 'Isoquinolines', 'Opiate Alkaloids', 'Papaverine and Derivatives', 'Parasympatholytics', 'Peripheral Nervous System Agents', 'Phosphodiesterase 4 Inhibitors', 'Phosphodiesterase Inhibitors', 'Sensory System Agents', 'Vasodilating Agents']" +DB00192,Indecainide,Indecainide is a rarely used antidysrhythmic. Indecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.,['Q14524'],Indecainide is a rarely used antidysrhythmic. Indecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.,CC(C)NCCCC1(C(N)=O)C2=CC=CC=C2C2=CC=CC=C12,"Indecainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.TargetActionsOrganismASodium channel protein type subunit alphainhibitorHumans",[],[] +DB00223,Diflorasone,"Diflorasoneis a topical corticosteroid used to treat the symptoms of various inflammatory skin conditions that cause erythema, pruritus, and discomfort.",['P04150'],"Like other topical corticosteroids, diflorasone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Diflorasone is a potent topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved.",[H][C@@]12C[C@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C,"The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase Ainhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A.TargetActionsOrganismAGlucocorticoid receptoragonistHumans",[],"['Adrenal Cortex Hormones', 'Anti-Inflammatory Agents', 'Corticosteroid Hormone Receptor Agonists', 'Corticosteroids', 'Corticosteroids, Dermatological Preparations', 'Corticosteroids, Potent (Group III)', 'Dermatologicals', 'Fused-Ring Compounds', 'Hormones', 'Hormones, Hormone Substitutes, and Hormone Antagonists', 'Immunosuppressive Agents', 'Pregnadienes', 'Pregnadienetriols', 'Pregnanes', 'Steroids', 'Steroids, Fluorinated']" +DB13346,Bufexamac,Bufexamacis an NSAID used to treat skin conditions like atopic eczema and inflammatory dermatoses.,"['P23219', 'P35354', 'Q9UBN7', 'Q969S8']","Bufexamac is a topically-active anti-inflammatory agent that inhibits the cyclooxygenase enzyme. In cutaneous and deep experimental inflammation, topical administration of bufexamac exerted a dose-related anti-inflammatory effect1. In guinea pigs, bufexamax was shown to be more active than topical acetylsalicylic acid 5% or phenylbutazone 5% in delaying the local increase in temperature resulting from UV exposure1. Bufexamac is unlikely to have any effect on wound healing1.",CCCCOC1=CC=C(CC(=O)NO)C=C1,"The full mechanism of action is unclear. It is proposed that bufexamac acts similarly to other non-steroidal anti-inflammatory drugs to inhibit prostaglandin biosynthesisin vitro, via inhibiting cyclo-oxygenase (COX) enzymes. Systematically administered bufexamac may accumulate preferentially in the adrenal cortex of rats and may play a role in adrenal stimulation; however its topical anti-inflammatory action is likely to be independent of this effect.TargetActionsOrganismAProstaglandin G/H synthase inhibitorHumansAProstaglandin G/H synthase inhibitorHumansUHistone deacetylase inhibitorHumansUHistone deacetylase inhibitorHumans",[],"['Acetamides', 'Acetic Acid Derivatives and Related Substances', 'Agents causing hyperkalemia', 'Amides', 'Amines', 'Analgesics', 'Analgesics, Non-Narcotic', 'Anti-Inflammatory Agents', 'Anti-Inflammatory Agents, Non-Steroidal', 'Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)', 'Antiinflammatory and Antirheumatic Products', 'Antiinflammatory and Antirheumatic Products, Non-Steroids', 'Antiinflammatory Preparations, Non-Steroids for Topical Use', 'Antineoplastic Agents', 'Antirheumatic Agents', 'Benzene Derivatives', 'Benzeneacetamides', 'Histone Deacetylase Inhibitors', 'Hydroxamic Acids', 'Hydroxy Acids', 'Hydroxylamines', 'Musculo-Skeletal System', 'Nephrotoxic agents', 'Non COX-2 selective NSAIDS', 'Peripheral Nervous System Agents', 'Sensory System Agents', 'Topical Products for Joint and Muscular Pain']" +DB09472,Sodium sulfate,Sodium sulfateis an agent used for bowel cleansing prior to colonoscopy or barium enema X-ray examination.,"['P00918', 'P00918', 'P00915', 'P00915']","Induces catharsis by the osmotic effects of the unabsorbed sulfate salts and polyethylene glycol (PEG) in the GI tract. Specifically, sulfate salts provide sulfate anions, which are poorly absorbed, and PEG, which is primarily unabsorbed, causes water to be retained in the GI tract resulting in watery diarrhea.",[Na+].[Na+].[O-]S([O-])(=O)=O,"MoviPrep produces a watery stool leading to cleansing of the colon. The osmotic activity of polyethylene glycol , sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid, when taken with liter of additional clear fluid, usually results in no net absorption or excretion of ions or water.TargetActionsOrganismACarbonic anhydrase inhibitorHumansACarbonic anhydrase inhibitorHumans",['Bowel preparation therapy'],"['Alimentary Tract and Metabolism', 'Anions', 'Drugs for Constipation', 'Drugs that are Mainly Renally Excreted', 'Electrolytes', 'Gastrointestinal Agents', 'Ions', 'Laxatives', 'Mineral Supplements', 'Osmotic Laxatives', 'Sodium', 'Sulfur Acids', 'Sulfur Compounds', 'Sulfuric Acids']" +DB01571,3-Methylfentanyl,"3-Methylfentanyl is an opioid analgesic and is an analog of the potent opioid, fentanyl. 3-Methylfentanyl is one of the most powerful opioid drugs sold illegally and is estimated to be between 400-6000 times more potent than morphine in certain cases. 3-Methylfentanyl was initially discovered in 1974 and widespread illegal use of this drug has occurred since this time.","['P35372', 'P41143', 'P41145']","3-Methylfentanyl exhibits similar pharmacodynamic effects to fentanyl but has been proven to be significantly stronger in these effects due to increased binding affinity to the opioid receptor. Fentanyl, administered alone, has a strong affinity for opioid receptors. 3-methylfentanyl has the potential to be extremely hazardous when used without the prescription and supervision of a medical professional. Ingestion of this drug has resulted in numerous deaths among individuals using the drug recreationally.",CCC(=O)N(C1CCN(CCC2=CC=CC=C2)CC1C)C1=CC=CC=C1,"Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP and OP receptor agonist). This results in hyperpolarization and reduced neuronal excitability.TargetActionsOrganismAMu-type opioid receptoragonistHumansADelta-type opioid receptoragonistHumansAKappa-type opioid receptoragonistHumans",[],"['Analgesics', 'Central Nervous System Agents', 'Peripheral Nervous System Agents', 'Piperidines', 'Sensory System Agents']" +DB04947,Altropane,"Boston Life Sciences (BLS) is developing Altropane as a potential radio-imaging agent to be used with single photon emission tomography (SPECT), for the early diagnosis of Parkinson's disease (PD) and attention deficit hyperactivity disorder (ADHD).",['Q01959'],"Altropane is a molecular-imaging agent that specifically binds to the dopamine transporter (DAT) protein found on the surface of dopamine-producing neurons, making it visible during SPECT imaging. Since most forms of Parkinsonian Syndromes result in a decreased number of dopamine-producing cells, it would be expected that these patients also have fewer DATs than do patients without PS. Thus, it is believed that altropane used in conjunction with SPECT imaging could be a useful test to distinguish Parkinsonian Syndrome tremors from non-Parkinsonian tremor: non-Parkinsonian patients would have more altropane-binding visible in the SPECT image, while Parkinsonian patients would have less.",[H][C@]12CC[C@]([H])([C@H]([C@H](C1)C1=CC=C(F)C=C1)C(=O)OC)N2C\C=C\I,"Positron emission tomography (PET) cameras are expensive and scarce, and the tests are non-reimbursable. A less costly and more available test such as a single photon emission computed tomography (SPECT) may be helpful in the diagnosis of early or atypical Parkinson's disease (PD) if its sensitivity is comparable to a PET scan. Altropane is an iodinated form of the N-allyl analog of WIN , which acts as a dopamine transport inhibitor. When radiolabeled with the gamma emitting isotope [I], altropane serves as a SPECT ligand with high affinity and selectivity for the dopamine transporter. It is a good marker for dopamine neurons and is useful in detecting PD.TargetActionsOrganismUSodium-dependent dopamine transporterNot AvailableHumans",[],"['Alkaloids', 'Aza Compounds', 'Azabicyclo Compounds', 'Iodine Radioisotopes', 'Tropanes']" +DB05676,Apremilast,Apremilastis a non-steroidal medication used for the treatment of inflammatory conditions such as psoriasis and psoriatic arthritis.,['Q86V67'],"Apremilast reduces but does not completely inhibit various inflammatory cytokines such as IL-1α, IL-6, IL-8, IL-10 MCP-1, MIP-1β, MMP-3, and TNF-α, relieving the symptoms of psoriasis and Behcet's disease, which are caused by an increase in these inflammatory mediators.6,13This drug has also been proven to be effective in relieving the pain associated with oral ulcers in Behcet's disease.11Apremilast may cause unwanted weight loss and worsen depression, leading to suicidal thoughts or actions. It is advisable to monitor for symptoms of depression and seek medical attention if they occur, especially in patients with pre-existing depression. The need for apremilast should be carefully assessed along with the risk of worsening depression and suicide. If weight loss occurs, the degree of weight loss should be evaluated, and consideration should be made for the possible discontinuation of apremilast.14",CCOC1=CC(=CC=C1OC)[C@@H](CS(C)(=O)=O)N1C(=O)C2=CC=CC(NC(C)=O)=C2C1=O,"The full mechanism of action of this drug is not fully established, however, it is known that apremilast is an inhibitor of phosphodiesterase (PDE), which mediates the activity of cyclic adenosine monophosphate (cAMP), a second messenger.The inhibition of PDE by apremilast leads to increased intracellular cAMP levels.An increase in cAMP results in the suppression of inflammation by decreasing the expression of TNF-α, IL-, IL-, and other inflammatory mediators. The above inflammatory mediators have been implicated in various psoriatic conditions as well as Behcet's disease, leading to their undesirable inflammatory symptoms such as mouth ulcers, skin lesions, and arthritis.,,Apremilast administration leads to a cascade which eventually decreases the levels of the above mediators, relieving inflammatory symptoms.TargetActionsOrganismAPhosphodiesterase isozyme antagonistHumans",[],"['Agents reducing cytokine levels', 'Anti-Inflammatory Agents', 'Antineoplastic and Immunomodulating Agents', 'Cytochrome P-450 CYP1A2 Substrates', 'Cytochrome P-450 CYP2A6 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Disease-modifying Antirheumatic Agents', 'Drugs that are Mainly Renally Excreted', 'Enzyme Inhibitors', 'Heterocyclic Compounds, Fused-Ring', 'Immunosuppressive Agents', 'Immunotherapy', 'Isoindoles', 'P-glycoprotein substrates', 'Phosphodiesterase 4 Inhibitors', 'Phosphodiesterase Inhibitors', 'Phthalimides', 'Selective Immunosuppressants']" +DB00145,Glycine,Glycineis an amino acid commonly used as a component of total parenteral nutrition and is also used as irrigation during surgery.,"['O75600', 'P13196', 'P22557', 'P41250', 'Q12879', 'Q14032', 'Q14330', 'P48637', 'Q14957', 'Q53ET4', 'Q6IB77', 'P34897', 'Q8WU03', 'Q969I3', 'Q9BYV1', 'Q9P0Z9', 'O60391', 'P23415', 'P21549', 'P48167', 'P34896', 'O75311', 'P23416', 'Q14749', 'P50440']",Helps trigger the release of oxygen to the energy requiring cell-making process; Important in the manufacturing of hormones responsible for a strong immune system.,NCC(O)=O,"In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia. Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.TargetActionsOrganismU-amino--ketobutyrate coenzyme A ligase, mitochondrialsubstrateHumansU-aminolevulinate synthase, nonspecific, mitochondrialsubstrateHumansU-aminolevulinate synthase, erythroid-specific, mitochondrialsubstrateHumansUGlycine--tRNA ligasesubstrateHumansUGlutamate receptor ionotropic, NMDA AantagonistHumansUBile acid-CoA:amino acid N-acyltransferasesubstrateHumansUN-arachidonyl glycine receptorsubstrateHumansUGlutathione synthetasesubstrateHumansUGlutamate receptor ionotropic, NMDA CagonistHumansUSerine hydroxymethyltransferaseproduct ofHumansUGlycine N-acyltransferasesubstrateHumansUSerine hydroxymethyltransferase, mitochondrialproduct ofHumansUGlycine N-acyltransferase-like protein substrateHumansUGlycine N-acyltransferase-like protein substrateHumansUAlanine--glyoxylate aminotransferase , mitochondrialproduct ofHumansUPeroxisomal sarcosine oxidaseproduct ofHumansUGlutamate receptor ionotropic, NMDA BsubstrateHumansUGlycine receptor subunit alpha-ligandHumansUSerine--pyruvate aminotransferasesubstrateHumansUGlycine receptor subunit betaligandHumansUSerine hydroxymethyltransferase, cytosolicproduct ofHumansUGlycine receptor subunit alpha-ligandHumansUGlycine receptor subunit alpha-ligandHumansUGlycine N-methyltransferasesubstrateHumansUGlycine amidinotransferase, mitochondrialsubstrateHumans","['Bladder distension', 'Bladder irrigation therapy', 'Irrigation therapy', 'Recovery', 'Amino acid supplementation']","['Amino Acids', 'Amino Acids, Peptides, and Proteins', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Dietary Supplements', 'Glycine Agents', 'Irrigating Solutions', 'Neurotransmitter Agents', 'Proteinogenic Amino Acids', 'Supplements']" +DB00348,Nitisinone,"Nitisinoneis a hydroxyphenylpyruvate dioxygenase inhibitor used as an adjunct to dietary restrictions for the treatment of hereditary tyrosinemia type 1 (HT-1), which causes intolerance to tyrosine containing foods.",['P32754'],"Hereditary tyrosinemia type 1 occurs due to a deficiency in fumarylacetoacetase (FAH), the final enzyme in the tyrosine catabolic pathway. Nitisinone inhibits catabolism of tyrosine by preventing the catabolic intermediates. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1.",[O-][N+](=O)C1=C(C=CC(=C1)C(F)(F)F)C(=O)C1C(=O)CCCC1=O,"Nitisinone is a competitive inhibitor of -hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolyase (FAH) in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with hereditary tyrosinemia type (HT-), nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate.TargetActionsOrganismA-hydroxyphenylpyruvate dioxygenaseinhibitorHumans",[],"['4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor', '4-Hydroxyphenylpyruvate Dioxygenase, antagonists & inhibitors', 'Acids, Carbocyclic', 'Alimentary Tract and Metabolism', 'Benzene Derivatives', 'Benzoates', 'Cyclohexanes', 'Cycloparaffins', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 Enzyme Inhibitors', 'Enzyme Inhibitors', 'Hydroxyphenylpyruvate Dioxygenase Inhibitors', 'Ketones', 'Other Miscellaneous Therapeutic Agents', 'Various Alimentary Tract and Metabolism Products']" +DB01251,Gliquidone,Gliquidoneis a sulfonylurea drug used in the management of diabetes mellitus type 2.,"['Q09428', 'Q15842']","Gliquidone is an anti-diabetic drug in the sulfonylurea class. In patients with diabetes mellitus, there is a deficiency or absence of a hormone manufactured by the pancreas called insulin. Insulin is the main hormone responsible for the control of sugar in the blood. Gliquidone is an antidiabetic medication which is used in those patients with adult maturity onset or non-insulin dependent diabetes (NIDDM). It works by lowering blood sugar levels by stimulating the production and release of insulin from the pancreas. It also promotes the movement of sugar from the blood into the cells in the body which need it.",COC1=CC2=C(C=C1)C(C)(C)C(=O)N(CCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1)C2=O,"The mechanism of action of gliquidone in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Gliquidone likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin.TargetActionsOrganismAATP-binding cassette sub-family C member inhibitorHumansAATP-sensitive inward rectifier potassium channel inhibitorHumans",[],"['Alimentary Tract and Metabolism', 'Amides', 'Blood Glucose Lowering Agents', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 Substrates', 'Drugs Used in Diabetes', 'Insulin Secretagogues', 'Oral Hypoglycemics', 'Sulfones', 'Sulfonylureas', 'Sulfur Compounds']" +DB06480,Prucalopride,Prucaloprideis a 5-HT4 receptor agonist indicated to treat adults with chronic idiopathic constipation.,['Q13639'],"In animal studies, prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon.4As well it has been shown that prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate. Thus, prucalopride not only accelerates the colonic transit but also accelerates gastric emptying and small bowel transit.2In supratherapeutic concentrations, prucalopride can be observed to interact with hERG potassium channels and L-type calcium channels.2In clinical trials, prucalopride showed to significantly increase the spontaneous bowel movements with a standardized mean difference of about 0.5 after the use of 1 mg when compared with the placebo group.5In this studies as well, it was observed a numerical improvement in mean colonic transit time and a significant increase in spontaneous complete bowel movement without marked changes in the anorectal function.5In phase III clinical trials, 86% of the tested individuals opted to continue with the open-label study and based on Patients Assessments, 67% of the patients increase more than one point improvement in their satisfaction.5In the final set of clinical trials for approval, there was a significant increase in the number of patients that reached over 3 complete spontaneous bowel movements per week when compared with the placebo.8",COCCCN1CCC(CC1)NC(=O)C1=C2OCCC2=C(N)C(Cl)=C1,"Prucalopride acts as a selective stimulator of the -HT receptors while having no interaction with hERG channel or -HT receptors which reduces significantly the cardiovascular risk found in other similar drugs.-HT receptors can be found throughout the gastrointestinal tract primarily in smooth muscle cells, enterochromaffin cells, and myenteric plexus. Its activation produces the release of acetylcholine which is the major excitatory neurotransmitter in the GI tract.Hence, prucalopride stimulates motility by interacting specifically with -HT receptors in the GI tract which causes a release of acetylcholine and further contraction of the muscle layer of the colon and relaxation of the circular muscle layer leading to the propulsion of luminal content.TargetActionsOrganismA-hydroxytryptamine receptor agonistHumans",[],"['Alimentary Tract and Metabolism', 'Antidepressive Agents', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates (strength unknown)', 'Cytochrome P-450 Substrates', 'Drugs for Constipation', 'Drugs that are Mainly Renally Excreted', 'Gastrointestinal Agents', 'Heterocyclic Compounds, Fused-Ring', 'Laxatives', 'Miscellaneous GI Drugs', 'Neurotransmitter Agents', 'P-glycoprotein substrates', 'Serotonin 4 Receptor Agonists', 'Serotonin 5-HT4 Receptor Agonists', 'Serotonin Agents', 'Serotonin Receptor Agonists', 'Serotonin-4 Receptor Agonist']" +DB04856,Dexloxiglumide,"Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist in phase III testing by Rottapharm in Europe only, as U.S. trials have been discontinued. As the D-isomer of loxiglumide, it retains all pharmacological properties of loxiglumide but is more potent.",['P32238'],"Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist. In October 2003, following the completion of two phase III clinical studies involving dexloxiglumide in women with constipation-predominant irritable bowel syndrome (IBS), Forest Laboratories decided to discontinue development of the drug for this indication. The results of the studies showed that dexloxiglumide did not show statistically significant favorability over placebo. Rotta Research is continuing a phase III trial of a different design in Europe for the IBS indication and also for gastroesophogeal reflux disease.",CCCCCN(CCCOC)C(=O)[C@@H](CCC(O)=O)NC(=O)C1=CC(Cl)=C(Cl)C=C1,"CCKA antagonists target receptors in the gastrointestinal system to increase gastric emptying and intestinal motility, as well as modulate intestinal sensitivity to distension.TargetActionsOrganismUCholecystokinin receptor type ANot AvailableHumans",[],"['Acids, Acyclic', 'Cytochrome P-450 CYP2B6 Substrates', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 CYP2C9 Substrates', 'Cytochrome P-450 CYP2E1 Substrates', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A5 Substrates', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Fatty Acids', 'Fatty Acids, Volatile', 'Lipids', 'Valerates']" +DB08890,Linaclotide,"Linaclotideis a guanylate cyclase-C agonist used to treat different types of constipation, such as irritable bowel syndrome-related constipation, idiopathic constipation, and functional constipation.",['P25092'],"Linaclotide is a laxative with visceral analgesic and secretory activities.9In animal studies and clinical trials, linaclotide improved constipation and gastrointestinal symptoms in patients with irritable bowel syndrome with predominant constipation and chronic idiopathic constipation.2In animal models, linaclotide has been shown to both accelerate gastrointestinal transit and reduce intestinal pain. In an animal model of visceral pain, linaclotide reduced abdominal muscle contraction and decreased the activity of pain-sensing nerves.7Taking linaclotide with a high-fat meal results in looser stools and a higher stool frequency than taking it in the fasted state.7Linaclotide binds to its target, guanylate cyclase-C (GC-C), with high affinity and selectivity. Linaclotide and its active metabolite act locally on the luminal surface of the intestinal epithelium.2,7As linaclotide is stable under a highly acidic pH environment, it acts in a pH-independent manner.1,2,3",[H][C@]1(CSSC[C@]2([H])NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CSSC[C@H](N)C(=O)N3)NC2=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)NCC(=O)N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O,"Linaclotide is a potent, highly selective agonist of guanylate cyclase-C (GC-C),a soluble and single-membrane-spanning enzyme on the luminal surface of intestinal epithelial cells. GC-C regulates chloride secretion.Linaclotide has a dual mode of action. Firstly, linaclotide and its active metabolite bind to transmembrane GC-C. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevated intracellular cGMP activates the cGMP-dependent protein kinase II (PKG-II), which phosphorylates and activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel expressed on the apical surface of intestinal epithelial cells.CFTR activation promotes the secretion of chloride and bicarbonate ions and inhibits sodium absorption, resulting in increased intestinal fluid and accelerated GI transit.,,Secondly, linaclotide exerts anti-nociceptive effects by reducing visceral hypersensitivity. Increased levels of extracellular cGMP in submucosa inhibit colonic nociceptors, relieving intestinal pain.,,TargetActionsOrganismAHeat-stable enterotoxin receptoragonistHumans",[],"['Alimentary Tract and Metabolism', 'Amino Acids, Peptides, and Proteins', 'Drugs for Constipation', 'Enzyme Activators', 'Gastrointestinal Agents', 'Guanylate Cyclase Activators', 'Guanylate Cyclase-C Agonist', 'Guanylyl Cyclase C Agonists', 'Laxatives', 'Miscellaneous GI Drugs']" +DB01046,Lubiprostone,Lubiprostoneis a prostaglandin derivative used to treat constipation caused by irritable bowel syndrome and opioid-use.,['P51788'],"Chronic idiopathic constipation is generally defined by infrequent or difficult passage of stool. The signs and symptoms associated with chronic idiopathic constipation (i.e., abdominal pain or discomfort, bloating, straining, and hard or lumpy stools) may be the result of abnormal colonic motility that can delay the transit of intestinal contents and impede the evacuation of rectal contents. One approach to the treatment of chronic idiopathic constipation is the secretion of fluid into the abdominal lumen through the activation of chloride channels in the apical membrane of the gastrointestinal epithelium. Lubiprostone is a locally acting chloride channel activator that increases intestinal chloride and fluid secretion without altering sodium and potassium concentrations in the serum.",[H][C@@]12CC(=O)[C@H](CCCCCCC(O)=O)[C@@]1([H])CC[C@@](O)(O2)C(F)(F)CCCC,"Lubiprostone acts by specifically activating ClC- chloride channels, which is a normal constituent of the apical membrane of the human intestine, in a protein kinase A action independent fashion. Activation of ClC- chloride channels causes an efflux of chloride ions into the lumen, which in turn leads to an efflux of sodium ions through a paracellular pathway to maintain isoelectric neutrality. As a result, water follows sodium into the lumen in order to maintain isotonic equilibrium, thereby increasing intestinal fluid secretion. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Activation of ClC- chloride channels may also stimulate the recovery of muscosal barrier function by restoring tight junction protein complexes in the intestine. Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium.TargetActionsOrganismAChloride channel protein inducerHumans",[],"['Alimentary Tract and Metabolism', 'Chloride Channel Agonists', 'Drugs for Constipation', 'Drugs that are Mainly Renally Excreted', 'Fatty Acids', 'Fatty Acids, Monounsaturated', 'Fatty Acids, Unsaturated', 'Laxatives', 'Lipids', 'Membrane Transport Modulators', 'Miscellaneous GI Drugs', 'Prostaglandins E']" +DB00551,Acetohydroxamic acid,Acetohydroxamic acidis a synthetic urea derivative used to treat urea splitting bacterial infections of the urinary tract.,"['P18314', 'P39900']","Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly.",CC(=O)NO,"Acetohydroxamic Acid reversibly inhibits the bacterial enzyme urease. This inhibits the hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms, leading to a decrease in pH and ammonia levels. As antimicrobial agents are more effective in such conditions, the effectiveness of these agents is amplified, resulting in a higher cure rate.TargetActionsOrganismAUrease subunit alphainhibitorEnterobacter aerogenesUMacrophage metalloelastaseinhibitorHumans",[],"['Amines', 'Enzyme Inhibitors', 'Genito Urinary System and Sex Hormones', 'Hydroxy Acids', 'Hydroxylamines', 'Urease Inhibitor', 'Urease Inhibitors', 'Urologicals']" +DB11581,Venetoclax,"Venetoclaxis a BCL-2 inhibitor used to treat chronic lymphocytic leukemia, small lymphocytic lymphoma, or acute myeloid leukemia.",['P10415'],"Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome5,Label,2. Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features6. This drug is not expected to have a significant impact on the cardiac QT intervalLabel. Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80%7.",CC1(C)CCC(CN2CCN(CC2)C2=CC=C(C(=O)NS(=O)(=O)C3=CC=C(NCC4CCOCC4)C(=C3)[N+]([O-])=O)C(OC3=CN=C4NC=CC4=C3)=C2)=C(C1)C1=CC=C(Cl)C=C1,"Proteins in the B cell CLL/lymphoma (BCL-) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL- and BCL--like (BCL-X(L)), which has demonstrated clinical efficacy in some BCL--dependent hematological cancers. Selective inhibition of BCL- by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia,. Venetoclax helps restore the process of apoptosis by binding directly to the BCL- protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-Label.TargetActionsOrganismAApoptosis regulator Bcl-antagonistinhibitorHumans",[],"['Amides', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCL-2 Inhibitor', 'BCRP/ABCG2 Inhibitors', 'BCRP/ABCG2 Substrates', 'Cytochrome P-450 CYP3A Inhibitors', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inhibitors', 'Cytochrome P-450 CYP3A4 Inhibitors (moderate)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index', 'Cytochrome P-450 Enzyme Inhibitors', 'Cytochrome P-450 Substrates', 'Increased Cellular Death', 'Narrow Therapeutic Index Drugs', 'OATP1B1/SLCO1B1 Inhibitors', 'P-glycoprotein inhibitors', 'P-glycoprotein substrates', 'P-glycoprotein substrates with a Narrow Therapeutic Index', 'Sulfones', 'Sulfur Compounds']" +DB01349,Tasosartan,Tasosartan is a long-acting angiotensin II (AngII) receptor blocker. Its long duration of action has been attributed to its active metabolite enoltasosartan. It is used to treat patients with essential hypertension.,"['P30556', 'P50052']","By blocking the angiotensin II (AT1) receptor, the drug ultimately causes vasodilation, reduced secretion of vasopressin (ADH), reduced production and secretion of aldosterone, amongst other actions leading to the combined effect of a reduction of blood pressure.",CC1=NC(C)=C2CCC(=O)N(CC3=CC=C(C=C3)C3=CC=CC=C3C3=NNN=N3)C2=N1,"Tasosartan is a selective, potent, orally active and long-acting nonpeptide Angiotensin II type (AT) receptor antagonist. Tasosartan blocks the renin-angiotensin-aldosterone system (RAAS) at the level of the AT receptor that mediates most, if not all, of the important actions of Ang II. Tasosartan binds reversibly to the AT receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. AT receptor antagonists avoid the nonspecificity of the Ang I converting enzyme (ACE) inhibitors.TargetActionsOrganismAType- angiotensin II receptorantagonistHumansUType- angiotensin II receptorantagonistHumans",[],"['Agents Acting on the Renin-Angiotensin System', 'Agents causing hyperkalemia', 'Angiotensin II receptor blockers (ARBs), plain', 'Angiotensin Receptor Antagonists', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates']" +DB01201,Rifapentine,Rifapentineis an antibiotic agent used in the treatment of pulmonary tuberculosis.,['P9WGY7'],"Rifapentine is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.",CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C2=C(C(O)=C3C)C(O)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C(\C=N\N1CCN(CC1)C1CCCC1)=C2O,"Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.TargetActionsOrganismADNA-directed RNA polymerase subunit beta'inhibitorMycobacterium tuberculosis",[],"['Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibiotics, Antitubercular', 'Antiinfectives for Systemic Use', 'Antimycobacterials', 'Cytochrome P-450 CYP2B6 Inducers', 'Cytochrome P-450 CYP2B6 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strong)', 'Cytochrome P-450 CYP2C8 Inducers', 'Cytochrome P-450 CYP2C8 Inducers (strength unknown)', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strength unknown)', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs for Treatment of Tuberculosis', 'Heterocyclic Compounds, Fused-Ring', 'Lactams, Macrocyclic', 'Leprostatic Agents', 'Rifamycin Antimycobacterial', 'Rifamycins']" +DB00576,Sulfamethizole,Sulfamethizoleis a sulfonamide antibiotic used to treat a wide variety of susceptible bacterial infections.,['P0AC13'],"Sulfamethizole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors ofp-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.",CC1=NN=C(NS(=O)(=O)C2=CC=C(N)C=C2)S1,Sulfamethizole is a competitive inhibitor of bacterial enzyme dihydropteroate synthetase. The normal para-aminobenzoic acid (PABA) substrate is prevented from binding. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.TargetActionsOrganismADihydropteroate synthaseinhibitorEscherichia coli (strain K),[],"['Amides', 'Amines', 'Aniline Compounds', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antibacterials for Systemic Use', 'Antiinfectives for Systemic Use', 'Benzene Derivatives', 'Benzenesulfonamides', 'Blood and Blood Forming Organs', 'Blood Substitutes and Perfusion Solutions', 'Cytochrome P-450 CYP2C9 Inhibitors', 'Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)', 'Cytochrome P-450 Enzyme Inhibitors', 'Dermatologicals', 'Genito Urinary System and Sex Hormones', 'Gynecological Antiinfectives and Antiseptics', 'Irrigating Solutions', 'Ophthalmologicals', 'Sensory Organs', 'Short-Acting Antibacterial Sulfonamides', 'Sulfanilamides', 'Sulfathiazoles', 'Sulfonamide Antibacterial', 'Sulfonamides', 'Sulfonamides and trimethoprim', 'Sulfones', 'Sulfur Compounds', 'Thiazoles']" +DB09460,Sodium carbonate,"Sodium Carbonate is the disodium salt of carbonic acid with alkalinizing property. When dissolved in water, sodium carbonate forms carbonic acid and sodium hydroxide. As a strong base, sodium hydroxide neutralizes gastric acid thereby acting as an antacid.","['P00915', 'P00918', 'P00918', 'P00918', 'P22748', 'P22748', 'Q16790', 'Q16790']","Alkalizing buffering action: Sodium bicarbonate is an alkalinizing agent that dissociates to provide bicarbonate ion. Bicarbonate in excess of that needed to buffer hydrogen ions causes systemic alkalinization and, when excreted, urine alkalinization as well. +Oral antacid action: Taken orally, sodium bicarbonate neutralizes stomach acid by the above mechanism.",[Na+].[Na+].[O-]C([O-])=O,"Carbon dioxide from the tissues diffuses rapidly into red blood cells, where it is hydrated with water to form carbonic acid. This reaction is accelerated by carbonic anhydrase, an enzyme present in high concentrations in red blood cells. The carbonic acid formed dissociates into bicarbonate and hydrogen ions. Most of the bicarbonate ions diffuse into the plasma. Since the ratio of HCO to dissolved CO is constant at equilibrium, pH may be expressed in terms of bicarbonate ion concentration and partial pressure of CO by means of the Henderson-Hasselbach equation: +pH = pk + log [HCO-]/aPCOTargetActionsOrganismUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumansUCarbonic anhydrase inhibitorHumans",[],"['Alkalies', 'Anions', 'Carbon Compounds, Inorganic', 'Carbonic Acid', 'Electrolytes', 'Ions']" +DB01597,Cilastatin,Cilastatinis a renal dehydropeptidase inhibitor used to prevent degradation of imipenem. Both medications are used together to treat a variety of infections.,['P16444'],"Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase.6,5Renal Dehydropeptidase degrades the antibioticimipenem. Cilastatin is therefore combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. However, cilastatin in and of itself does not have any antibacterial activity. The increased renal excretion of unchanged imipenem appears to prevent proximal tubular necrosis associated with high doses of imipenem.2",CC1(C)C[C@@H]1C(=O)N\C(=C/CCCCSC[C@H](N)C(O)=O)C(O)=O,"Cilastatin is a renal dehydropeptidase-I inhibitor.,Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to block the metabolism of imipenem.TargetActionsOrganismADipeptidase inhibitorHumans",[],"['Cycloparaffins', 'Cyclopropanes', 'Dipeptidase Inhibitors', 'Enzyme Inhibitors', 'OAT1/SLC22A6 inhibitors', 'OAT3/SLC22A8 Inhibitors', 'Protease Inhibitors', 'Renal Dehydropeptidase Inhibitor']" +DB01353,Butobarbital,Butobarbital is a sedative and a hypnotic drug.,"['P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P14867', 'P43681', 'P36544', 'P42262', 'Q13002']",Butethal (also known as butobarbitone and butobarbital) belongs to a group of medicines called the barbiturates. It is thought to act on receptors in the brain (GABA receptors) causing the release of the chemical GABA. This chemical inhibits certain areas of the brain resulting in sleepiness.,CCCCC1(CC)C(=O)NC(=O)NC1=O,"Butethal binds at a distinct binding site associated with a Cl-ionopore at the GABAAreceptor, increasing the duration of time for which the Cl-ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.TargetActionsOrganismAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansAGamma-aminobutyric acid receptor subunit alpha-potentiatorHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUNeuronal acetylcholine receptor subunit alpha-antagonistHumansUGlutamate receptor antagonistHumansUGlutamate receptor ionotropic, kainate antagonistHumans",[],"['Anticholinergic Agents', 'Barbiturates, Plain', 'Central Nervous System Agents', 'Central Nervous System Depressants', 'Hypnotics and Sedatives', 'Nervous System', 'Nicotinic Antagonists', 'Psycholeptics', 'Pyrimidines', 'Pyrimidinones']" +DB11901,Apalutamide,Apalutamideis an androgen receptor inhibitor used to treat non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer.,"['P10275', 'P14867', 'P47869', 'P34903', 'P48169', 'P31644', 'Q16445', 'P18505', 'P47870', 'P28472', 'O14764', 'P78334', 'Q8N1C3', 'P18507', 'Q99928', 'O00591', 'Q9UN88']","In androgen receptors (AR)-overexpressing LNCaP cells, apaludatamide was reported to have a 7 to 10-fold greater affinity to the AR than bicalutamide.3Additionally, apalutamide still possesses total antagonistic activity in AR-overexpressing cell lines with bicalutamide-resistance mutations such as T878A and W741C.4In castrate mice with LNCaP/AR(cs) tumors, apalutamide produced tumor regression (defined by >50% regression in tumor volume) in 8 mice compared to only 1 for bicalutamide.2The apalutamide-treated tumors also have a 60% decrease in proliferative index and a 10-fold increase in apoptotic rate compared with vehicle.2In an open-label, uncontrolled, multicenter, single-arm dedicated QT study in 45 patients with CRPC, an exposure-QT analysis suggested a concentration-dependent increase in QTcF for apalutamide and its active metabolite. Apalutamide demonstrated antitumor activity in the mouse xenograft models of prostate cancer, where it decreased tumor cell proliferation and reduced tumor volume.6",CNC(=O)C1=CC=C(C=C1F)N1C(=S)N(C(=O)C11CCC1)C1=CC(=C(N=C1)C#N)C(F)(F)F,"Persistent androgen receptor (AR) signaling is a common feature of castration-resistant prostate cancer (CRPC), attributed to AR gene amplification, AR gene mutation, increased AR expression, or increased androgen biosynthesis in prostate tumors.Apalutamide is an antagonist of AR that binds directly to the ligand-binding domain of the AR with the IC of nM. Upon binding, apalutamide disrupts AR signalling, inhibits DNA binding, and impedes AR-mediated gene transcription.Apalutamide impairs the translocation of AR from the cytoplasm to the nucleus thus reducing the concentrations of AR available to interact with the androgen response elements (AREs).Upon treatment with apalutamide, AR was not recruited to the DNA promoter regions.Its main metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third of the activity of apalutamide in an in vitro transcriptional reporter assay.TargetActionsOrganismAAndrogen receptorantagonistHumansNGABA(A) ReceptorantagonistHumans",['Androgen Deprivation Therapy'],"['Androgen Receptor Inhibitors', 'Antiandrogens', 'Antineoplastic Agents', 'Antineoplastic and Immunomodulating Agents', 'BCRP/ABCG2 Inducers', 'Cytochrome P-450 CYP2C19 Inducers', 'Cytochrome P-450 CYP2C19 Inducers (strong)', 'Cytochrome P-450 CYP2C8 Substrates', 'Cytochrome P-450 CYP2C9 Inducers', 'Cytochrome P-450 CYP2C9 Inducers (weak)', 'Cytochrome P-450 CYP3A Inducers', 'Cytochrome P-450 CYP3A Inducers (strong)', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Inducers', 'Cytochrome P-450 CYP3A4 Inducers (strong)', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Enzyme Inducers', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Endocrine Therapy', 'Hormone Antagonists and Related Agents', 'Imidazoles', 'Imidazolidines', 'MATE 1 Inhibitors', 'MATE 2 Inhibitors', 'MATE inhibitors', 'OAT3/SLC22A8 Inhibitors', 'OATP1B1/SLCO1B1 Inducers', 'OCT2 Inhibitors', 'P-glycoprotein inducers', 'Prostatic Neoplasms, drug therapy']" +DB06282,Levocetirizine,Levocetirizineis an H1-receptor antagonist used to treat symptoms associated with chronic allergic rhinitis and uncomplicated cases of chronic idiopathic urticaria.,['P35367'],"Levocetirizine is a second generation histamine H1antagonist used to treat various allergic symptoms.2,3,4It has a long duration of action as it is generally taken once daily, and a wide therapeutic window as animal studies show the maximal nonlethal dose is over 100x a normal dose.4Patients are cautioned to avoid tasks that require complete alertness, avoid alertness, and use caution in patients with factors predisposing urinary retention.4",OC(=O)COCCN1CCN(CC1)[C@H](C1=CC=CC=C1)C1=CC=C(Cl)C=C1,"Levocetirizine selectively inhibits histamine Hreceptors.This action prevents histamine from activating this receptor and causing effects like smooth muscle contraction, increased permeability of vascular endothelium, histidine uptake in basophils, stimulation of cough receptors, and stimulation of flare responses in the nervous system.TargetActionsOrganismAHistamine H receptorantagonistinhibitorHumans",[],"['Antihistamines for Systemic Use', 'Central Nervous System Depressants', 'Cytochrome P-450 CYP3A Substrates', 'Cytochrome P-450 CYP3A4 Substrates', 'Cytochrome P-450 Substrates', 'Drugs that are Mainly Renally Excreted', 'Histamine Agents', 'Histamine Antagonists', 'Histamine H1 Antagonists', 'Histamine H1 Antagonists, Non-Sedating', 'Neurotransmitter Agents', 'Piperazine Derivatives', 'Piperazines', 'Potential QTc-Prolonging Agents', 'QTc Prolonging Agents']"