Tartaric acid  is a white, crystalline  organic acid  that occurs naturally in many fruits, most notably in  grapes  but also in  tamarinds ,  bananas ,  avocados ,  and  citrus . [ 1 ]  Its  salt ,  potassium bitartrate , commonly known as cream of tartar, develops naturally in the process of  fermentation . Potassium bitartrate is commonly mixed with  sodium bicarbonate  and is sold as  baking powder  used as a  leavening agent  in food preparation. The acid itself is added to foods as an  antioxidant   E334  and to impart its distinctive sour taste.  Naturally occurring  tartaric acid is a useful raw material in  organic synthesis . Tartaric acid, an alpha-hydroxy- carboxylic acid , is  diprotic  and  aldaric  in acid characteristics and is a dihydroxyl derivative of  succinic acid .


Tartaric acid has been known to  winemakers  for centuries. However, the chemical process for extraction was developed in 1769 by the  Swedish  chemist  Carl Wilhelm Scheele . [ 4 ]


Tartaric acid played an important role in the discovery of  chemical chirality . This property of tartaric acid was first observed in 1832 by  Jean Baptiste Biot , who observed its ability to rotate  polarized light . [ 5 ] [ 6 ]   Louis Pasteur  continued this research in 1847 by investigating the shapes of  sodium ammonium tartrate  crystals, which he found to be chiral. By manually sorting the differently shaped crystals, Pasteur was the first to produce a pure sample of levotartaric acid. [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]


Naturally occurring form of the acid is  dextro tartaric acid   or  L -(+)-tartaric acid  (obsolete name  d -tartaric acid).  Because it is available naturally, it is cheaper than its  enantiomer  and the  meso isomer . The  dextro  and  levo  prefixes are archaic terms. [ 12 ]  Modern textbooks refer to the natural form as (2 R ,3 R )-tartaric acid  ( L -(+)-tartaric acid) , and its enantiomer as (2 S ,3 S )-tartaric acid  ( D -(-)-tartaric acid) .  The  meso  diastereomer is referred to as (2 R ,3 S )-tartaric acid or (2 S ,3 R )-tartaric acid.


Tartaric acid in  Fehling's solution  binds to copper(II) ions, preventing the formation of insoluble hydroxide salts.


The  L -(+)-tartaric acid isomer of tartaric acid is industrially produced in the largest amounts. It is obtained from  lees , a solid byproduct of fermentations. The former byproducts mostly consist of potassium bitartrate ( KHC 4 H 4 O 6 ). This potassium salt is converted to  calcium tartrate  ( CaC 4 H 4 O 6 ) upon treatment with  calcium hydroxide  ( Ca(OH) 2 ): [ 20 ]


In practice, higher yields of calcium tartrate are obtained with the addition of  calcium sulfate .  Calcium tartrate is then converted to tartaric acid by treating the salt with aqueous sulfuric acid:


Racemic tartaric acid can be prepared in a multistep reaction from  maleic acid . In the first step, the maleic acid is  epoxidized  by  hydrogen peroxide  using  potassium tungstate  [ de ]  as a catalyst. [ 20 ]


In the next step, the epoxide is hydrolyzed.


A mixture of racemic acid and  meso -tartaric acid is formed when  dextro -Tartaric acid is heated in water at 165 °C for about 2 days.  meso -Tartaric acid can also be prepared from dibromosuccinic acid using silver hydroxide: [ 21 ]


meso -Tartaric acid can be separated from residual racemic acid by crystallization, the racemate being less soluble.


L-(+)-tartaric acid, can participate in several reactions. As shown the reaction scheme below, dihydroxymaleic acid is produced upon treatment of L-(+)-tartaric acid with hydrogen peroxide in the presence of a  ferrous  salt.


Dihydroxymaleic acid  can then be oxidized to  tartronic acid  with nitric acid. [ 22 ]


Important derivatives of tartaric acid include:


Tartaric acid is a  muscle   toxin , which works by inhibiting the production of  malic acid , and in high doses causes paralysis and death. [ 26 ]  The  median lethal dose  (LD 50 ) is about 7.5 grams/kg for a human, 5.3 grams/kg for rabbits, and 4.4 grams/kg for mice. [ 27 ]  Given this figure, it would take over 500 g (18 oz) to kill a person weighing 70 kg (150 lb) with 50% probability, so it may be safely included in many foods, especially sour-tasting  sweets . As a  food additive , tartaric acid is used as an  antioxidant  with  E number   E334 ;  tartrates  are other additives serving as antioxidants or  emulsifiers .


When cream of tartar is added to water, a suspension results which serves to clean copper  coins  very well, as the tartrate solution can dissolve the layer of copper(II) oxide present on the surface of the coin. The resulting copper(II)-tartrate complex is easily soluble in water.


Tartaric acid may be most immediately recognizable to wine drinkers as the source of "wine diamonds", the small  potassium bitartrate  crystals that sometimes form spontaneously on the  cork  or bottom of the bottle. These "tartrates" are harmless, despite sometimes being mistaken for broken glass, and are prevented in many wines through  cold stabilization  (which is not always preferred since it can change the wine's profile). The tartrates remaining on the inside of  aging barrels  were at one time a major industrial source of potassium bitartrate.


Tartaric acid plays an important role chemically, lowering the pH of fermenting "must" to a level where many undesirable spoilage bacteria cannot live, and acting as a preservative after  fermentation . In the mouth, tartaric acid provides some of the tartness in the wine, although  citric  and  malic acids  also play a role.


Grapes and tamarinds have the highest levels of tartaric acid concentration. Other fruits with tartaric acid are  bananas ,  avocados ,  prickly pear  fruit,  apples ,  cherries ,  papayas ,  peaches ,  pears ,  pineapples ,  strawberries ,  mangoes   and  citrus fruits . [ 1 ] [ 28 ]


Trace amounts of tartaric acid have been found in  cranberries  and other  berries . [ 29 ]


Tartaric acid is also present in the leaves and pods of  Pelargonium  plants and  beans .


Tartaric acid and its derivatives have a plethora of uses in the field of pharmaceuticals. For example, it has been used in the production of effervescent salts, in combination with citric acid, to improve the taste of oral medications. [ 22 ]  The potassium antimonyl derivative of the acid known as tartar emetic is included, in small doses, in  cough syrup  as an  expectorant .


Tartaric acid also has several applications for industrial use. The acid has been observed to  chelate  metal ions such as calcium and magnesium. Therefore, the acid has served in the farming and metal industries as a chelating agent for complexing micronutrients in soil  fertilizer  and for cleaning metal surfaces consisting of aluminium, copper, iron, and alloys of these metals, respectively. [ 20 ]


While tartaric acid is well-tolerated by humans and lab animals, an April 2021 letter to the editor of  JAVMA  hypothesized that the tartaric acid in grapes could be the cause of  grape and raisin toxicity in dogs . [ 30 ] [ 31 ]  Other studies have observed tartaric acid toxicity in kidney cells of dogs, but not in human kidney cells. [ 32 ]


In dogs, the tartaric acid of  tamarind  causes  acute kidney injury , which can often be fatal. [ 33 ]


A review identified a relationship between grape ingestion and illness, though the specific type or quantity of grapes that cause toxicity remains unclear. Grape ingestion commonly leads to gastrointestinal and/or renal issues, with treatment depending on the symptoms; outcomes can vary. [ 34 ]


Tendril perversion  is a geometric phenomenon sometimes observed in  helical  structures in which the direction of the helix transitions between left-handed and right-handed. [ 1 ]   [ 2 ]  Such a reversal of  chirality  is commonly seen in helical plant  tendrils  and  telephone handset  cords. [ 3 ]


The phenomenon was known to  Charles Darwin , [ 4 ]  who wrote in 1865,


A tendril ... invariably becomes twisted in one part in one direction, and in another part in the opposite direction ...
This curious and symmetrical structure has been noticed by several botanists, but has not been sufficiently
explained. [ 5 ]


The term "tendril perversion" was coined by  Alain Goriely  and Michael Tabor in 1998 based on the word  perversion  found in 19th-century science literature. [ 6 ] [ 7 ]  "Perversion" is a transition from one chirality to another and was known to  James Clerk Maxwell , who attributed it to  topologist   J. B. Listing . [ 4 ] [ 8 ]


Tendril perversion can be viewed as an example of  spontaneous symmetry breaking , in which the strained structure of the tendril adopts a  configuration of minimum energy  while preserving zero overall twist. [ 2 ]


Tendril perversion has been studied both experimentally and theoretically. Gerbode et al. have made experimental studies of the coiling of  cucumber  tendrils. [ 9 ] [ 10 ]  A detailed study of a simple model of the physics of tendril perversion was made by McMillen and Goriely in the early 2000s. [ 2 ]  Liu et al. showed in 2014 that "the transition from a helical to a hemihelical shape, as well as the number of perversions, depends on the height to width ratio of the strip's cross-section." [ 3 ]


Generalized tendril perversions were put forward by Silva et al., to include perversions that can be intrinsically produced in elastic filaments, leading to a multiplicity of geometries and dynamical properties. [ 11 ]


Thalidomide , sold under the brand names  Contergan  and  Thalomid  among others, is an  oral  medication used to treat a number of cancers (e.g.,  multiple myeloma ),  graft-versus-host disease , and many  skin disorders  (e.g., complications of  leprosy  such as  skin lesions ). [ 6 ] [ 7 ]  Thalidomide has been used to treat conditions associated with  HIV :  aphthous ulcers , HIV-associated  wasting syndrome , diarrhea, and  Kaposi's sarcoma , but increases in HIV viral load have been reported. [ 6 ]


Common side effects include  sleepiness ,  rash , and  dizziness . [ 6 ]  Severe side effects include  tumor lysis syndrome ,  blood clots , and  peripheral neuropathy . [ 8 ]  Thalidomide is a known human  teratogen  and carries an extremely high risk of severe, life-threatening birth defects if administered or taken during pregnancy. [ 6 ]  It causes skeletal deformities such as  amelia  (absence of legs and/or arms), absence of bones, and  phocomelia  (malformation of the limbs). A single dose of thalidomide, regardless of dosage, is enough to cause  teratogenic  effects. [ 6 ]


Thalidomide was first marketed in 1957 in West Germany, where it was available  over-the-counter . [ 9 ] [ 10 ]  When first released, thalidomide was promoted for  anxiety ,  trouble sleeping , "tension", and  morning sickness . [ 10 ] [ 11 ]  While it was initially thought to be safe in pregnancy,  concerns regarding birth defects  arose, resulting in its removal from the market in Europe in 1961. [ 9 ] [ 10 ]  The total number of infants severely harmed by thalidomide use during pregnancy is estimated at over 10,000, possibly 20,000, of whom about 40% died around the time of birth. [ 6 ] [ 10 ]  Those who survived had limb, eye, urinary tract, and heart problems. [ 9 ]  Its initial entry into the US market was prevented by  Frances Kelsey , a reviewer at the FDA. [ 11 ]  The birth defects caused by thalidomide led to the development of greater  drug regulation  and monitoring in many countries. [ 9 ] [ 11 ]


It was approved in the United States in 1998 for use as a treatment for cancer. [ 6 ]  It is on the  World Health Organization's List of Essential Medicines . [ 12 ]  It is available as a  generic medication . [ 8 ] [ 13 ]


Thalidomide is used as a first-line treatment for  multiple myeloma  in combination with  dexamethasone  or with  melphalan  and  prednisone  to treat acute episodes of  erythema nodosum leprosum , as well as for maintenance therapy. [ 14 ] [ 15 ]


The bacterium that causes  tuberculosis  (TB) is related to  leprosy . Thalidomide may be helpful in some cases where  standard TB drugs  and  corticosteroids  are not sufficient to resolve severe inflammation in the brain. [ 16 ] [ 17 ]


It is used as a second-line treatment to manage  graft-versus-host disease  and  aphthous stomatitis  in children and has been prescribed for other conditions in children, including  actinic prurigo  and  epidermolysis bullosa ; the evidence for these uses is weak. [ 18 ]   It is recommended only as a third line treatment in graft-versus-host-disease in adults because of lack of efficacy and side effects observed in clinical trials. [ 19 ] [ 20 ]


Prescriptions of thalidomide are accompanied by strict measures to avoid any possibility of use during pregnancy, and thalidomide should be avoided in women wanting to conceive. [ 21 ]  In the United States, the prescribing doctor is required to ensure that  contraception  is being used and that regular pregnancy tests are taken. [ 15 ] [ 14 ]


Thalidomide  causes birth defects . [ 14 ] [ 15 ] [ 22 ] [ 23 ]  The U.S.  Food and Drug Administration  (FDA) and other regulatory agencies have approved marketing of the drug only with an auditable  risk evaluation and mitigation strategy  that ensures that people using the drug are aware of the risks and avoid pregnancy; this applies to both men and women, as the drug can be transmitted in  semen . [ 22 ] [ failed verification ] [ 21 ]


There is a high risk that thalidomide can cause excessive  blood clots . There is also a high risk that thalidomide can interfere with the production of several types of new blood cells, creating a risk of infection via  neutropenia ,  leukopenia , and  lymphopenia , and risks that blood will not clot via  thrombocytopenia . There is also a risk of  anemia  via lack of red blood cells.  The drug can also damage nerves, causing potentially irreversible  peripheral neuropathy . [ 14 ] [ 15 ]


Thalidomide has several adverse cardiovascular effects, including risk of  heart attacks ,  pulmonary hypertension , and changes in heart rhythm, such as  syncope ,  bradycardia , and  atrioventricular block . [ 14 ] [ 15 ]


Thalidomide can cause  liver damage  and severe skin reactions like  Stevens–Johnson syndrome . It tends to make people sleepy, which creates risk when driving and operating other machinery. As it kills cancer cells, it can cause  tumor lysis syndrome . Thalidomide can  prevent menstruation . [ 14 ] [ 15 ]


In addition, very common (reported in more than 10% of people) adverse effects include  tremor , dizziness, tingling, numbness, constipation, and  peripheral edema . [ 14 ] [ 15 ]


Common adverse effects (reported by 1–10% of people) include confusion, depressed mood, reduced coordination, heart failure, difficulty breathing, interstitial lung disease, lung inflammation, vomiting, dry mouth, rashes, dry skin, fever, weakness, and a sense of unwellness. [ 14 ] [ 15 ]


There are no expected  pharmacokinetic  interactions between thalidomide and other medicines due to its neutral effects on  P-glycoprotein  and the  cytochrome P450  family.  It may interact with sedatives due to its sedative action and bradycardic agents, like beta-blockers, due to its bradycardia-inducing effects. The risk of  peripheral neuropathy  may be increased by concomitant treatment of thalidomide with other agents known to cause peripheral neuropathy. [ 24 ]  The risk of  venous thromboembolisms  with thalidomide seems to be increased when patients are treated with  oral contraceptives  or other cytotoxic agents (including  doxorubicin  and  melphalan ) concurrently. Thalidomide may interfere with various contraceptives, and hence it is advised that women of reproductive age use at least two different means of contraception to ensure that no child will be conceived while they are taking thalidomide. [ 14 ] [ 15 ] [ 24 ]


As of 2013, eighteen cases of overdoses had been reported with doses of up to 14.4 grams, none of them fatal. [ 24 ]  No specific antidote for overdose exists and treatment is purely  supportive . [ 24 ]


The precise mechanism of action for thalidomide was not known until the twenty-first century, [ 25 ]  although efforts to identify thalidomide's  teratogenic  action generated more than 2,000 research papers and the proposal of 15 or 16 plausible mechanisms by 2000. [ 26 ]  The primary mechanism of action of thalidomide and its analogs in both their anti-cancer and teratogenic effects is now known to be as  cereblon   E3 ligase  modulators. [ 25 ] [ 27 ] [ 28 ] [ 29 ]


Thalidomide also binds to and acts as an  antagonist  of the  androgen receptor  and hence is a  nonsteroidal antiandrogen  of some capacity. [ 30 ]  In accordance, it can produce  gynecomastia  and  sexual dysfunction  as side effects in men. [ 31 ]


Thalidomide is provided as a  racemic mixture  of two  enantiomers ; while there are reports that only one of the enantiomers may cause birth defects, the body converts each enantiomer into the other through mechanisms that are not well understood. [ 22 ]  The (R)-enantiomer has the desired sedative effect while the (S)-enantiomer harbors embryo-toxic and teratogenic effects. Attempting to extract solely  R -thalidomide does not remove the risk of birth defects, as it was demonstrated that the "safe"  R -thalidomide undergoes an  in vivo   chiral inversion  to the "teratogenic"  S -thalidomide. Under biological conditions, the enantiomers interconvert ( bidirectional chiral inversion  – (R)- to (S)- and vice versa). [ 32 ] [ 33 ]


Thalidomide is  racemic ; while  S -thalidomide is the bioactive form of the molecule, the individual enantiomers can  racemize  to each other due to the acidic hydrogen at the  chiral centre , which is the carbon of the  glutarimide  ring bonded to the  phthalimide   substituent . The racemization process can occur  in vivo . [ 5 ] [ 34 ] [ 35 ] [ 36 ]  The process of conversion of one enantiomer to its mirror-image version with no other change in the molecule is called chiral inversion. [ 37 ]


Celgene Corporation  originally synthesized thalidomide using a three-step sequence starting with  L -glutamic acid  treatment, but this has since been reformed by the use of  L -glutamine . [ 38 ]  As shown in the image below,  N -carbethoxyphthalimide (1) can react with  L -glutamine to yield  N -phthaloyl- L -glutamine (2). Cyclization of  N -phthaloyl- L -glutamine occurs using  carbonyldiimidazole , which then yields thalidomide (3). [ 38 ]  Celgene Corporation's original method resulted in a 31% yield of  S -thalidomide, whereas the two-step synthesis yields 85–93% product that is 99% pure. [ citation needed ]


In 2023, it is reported that  phthalic anhydride  and  L -glutamine  under suitable conditions can react directly to form thalidomide. In the procedure, phthalic anhydride and  L -glutamine are grounded and added into  toluene  solvent. The solution, along with  triethylamine  and  acetic anhydride , is refluxed at ~110°C for 9 hours; after that the solution goes through a simple  vacuum filtration  procedure to obtain the product. [ 39 ]


In 1952, thalidomide was synthesised by  Chemical Industry Basel , but was found "to have no effect on animals" and was discarded on that basis. [ 40 ]   In 1957, it was acquired by  Chemie Grünenthal  in Germany. [ 40 ]  The German company had been established as a soap maker after World War II ended, to address the urgent market need for antibiotics. [ 41 ]   Heinrich Mückter [ 42 ]  was appointed to head the discovery program based on his experience working with the German army's antiviral research. While preparing  reagents  for the work, Mueckter's assistant Wilhelm Kunz isolated a by-product that was recognized by pharmacologist Herbert Keller as an analog of  glutethimide , a  sedative . The medicinal chemistry work turned to improving the lead compound into a suitable drug: the result was thalidomide. The toxicity was examined in several animals, and the drug was introduced in 1956 as a sedative, but it was never tested on pregnant women. [ 43 ]


Researchers at Chemie Grünenthal found that thalidomide was a particularly effective  antiemetic  that had an inhibitory effect on  morning sickness . [ 44 ]  On 1 October 1957, the company launched thalidomide and began marketing it under the trade name Contergan. [ 45 ] [ 46 ]  It was proclaimed a "wonder drug" for  insomnia , coughs, colds and headaches. [ 47 ]


During that period, the use of medications during pregnancy was not strictly controlled, and drugs were not thoroughly tested for potential harm to the  fetus . [ 44 ]  Thousands of pregnant women took the drug to relieve their symptoms. At the time of the drug's development, scientists did not believe any drug taken by a pregnant woman could pass across the  placental barrier  and harm the developing fetus. [ 48 ]  There soon appeared reports of abnormalities in children being born to mothers using thalidomide. In late 1959, it was noticed that  peripheral neuritis  developed in patients who took the drug over a period of time, and it was only after this point that thalidomide ceased to be provided over the counter. [ 49 ]


While initially considered safe, the drug was responsible for  teratogenic  deformities in children born after their mothers used it during pregnancies, prior to the third trimester. In November 1961, thalidomide was taken off the market due to massive pressure from the press and public. [ 50 ]  Experts estimate that thalidomide led to the death of approximately 2,000 children and serious birth defects in more than 10,000 children, with over half of them in West Germany. [ 51 ]  The regulatory authorities in  East Germany  never approved thalidomide. [ 52 ]  One reason for the initially unobserved side effects of the drug and the subsequent approval in West Germany was that at that time drugs did not have to be tested for teratogenic effects. They were tested for toxicity on rodents only, as was usual at the time. [ 53 ]


In the UK, the British pharmaceutical company  The Distillers Company  (Biochemicals) Ltd, a subsidiary of Distillers Co. Ltd (now part of  Diageo plc ), marketed thalidomide throughout the UK, Australia, and New Zealand, under the brand name Distaval, as a remedy for  morning sickness . Their advertisement claimed that "Distaval can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child ... Outstandingly safe Distaval has been prescribed for nearly three years in this country." [ 52 ]  Globally, more pharmaceutical companies started to produce and market the drug under license from Chemie Grünenthal. By the mid-1950s, 14 pharmaceutical companies were marketing thalidomide in 46 countries under at least 37 different trade names. [ citation needed ]


In the US, representatives from Chemie Grünenthal approached  Smith, Kline & French  (SKF), now  GlaxoSmithKline , with a request to market and distribute the drug in North America. A memorandum, rediscovered in 2010 in the archives of the FDA, shows that in 1956–57, as part of its in-licensing approach, Smith, Kline and French conducted animal tests and ran a clinical trial of the drug in the US involving 875 people, including pregnant women. [ 54 ]  In 1956, researchers involved in clinical trials at SKF noted that, even when used in very high doses, thalidomide could not induce sleep in mice. [ citation needed ]  When administered at doses 50 to 650 times larger than that claimed by Chemie Grünenthal to be "sleep-inducing", the researchers could still not achieve the hypnotic effect in animals that it had on humans. [ citation needed ]  After completion of the trial, and based on reasons kept hidden for decades, SKF declined to commercialize the drug. In 1958, Chemie Grünenthal reached an agreement with the William S. Merrell Company in Cincinnati, Ohio ( later Richardson-Merrell , now part of  Sanofi ), to market and distribute thalidomide throughout the US. [ 52 ]


The US FDA refused to approve thalidomide for marketing and distribution. However, the drug was distributed in large quantities for testing purposes, after the American distributor and manufacturer  Richardson-Merrell  had applied for its approval in September 1960. [ citation needed ]  The official in charge of the FDA review,  Frances Oldham Kelsey , did not rely on information from the company, which did not include any test results. Richardson-Merrell was called on to perform tests and report the results. The company demanded approval six times and was refused each time. The distribution for "testing" resulted in 17 children born in the US with thalidomide-induced malformations. Oldham Kelsey was awarded the  President's Award for Distinguished Federal Civilian Service  by President Kennedy in 1962 for not allowing thalidomide to be approved for sale in the US. She was also inducted into the  National Women's Hall of Fame  in 2000. [ 55 ]


Canada's Food and Drug Directorate approved the sale of thalidomide by prescription in November 1960. [ 56 ]  There were many different forms sold: Kevadon, produced by the William S. Merrell Company seeking approval for its thalidomide product, was released on the market in April 1961, and the most common variant (Horner's Talimol) was put on the market on October 23 of the same year. [ 57 ]  Two months after Talimol went on sale, pharmaceutical companies sent physicians letters warning about the risk of birth defects. [ 57 ]  It was not until March 1962 that both drugs were banned from the Canadian market by the directorate, and soon afterward physicians were warned to destroy their supplies. [ 57 ]


In 1964, Israeli physician  Jacob Sheskin  administered thalidomide to a patient critically ill with  leprosy . The patient exhibited  erythema nodosum leprosum  (ENL), a painful skin condition, one of the complications of leprosy. The treatment was attempted despite the ban on thalidomide's use, and the results were favourable: the patient slept for hours and was able to get out of bed without aid upon awakening. A clinical trial studying the use of thalidomide in leprosy soon followed. [ 58 ]


Thalidomide has been used by Brazilian physicians as the drug of choice for the treatment of severe ENL since 1965, and by 1996, at least 33 cases of thalidomide embryopathy were recorded in people born in Brazil after 1965. [ 59 ]  Since 1994, the production, dispensing, and prescription of thalidomide have been strictly controlled, requiring women to use two forms of birth control and submit to regular pregnancy tests. Despite this, cases of thalidomide embryopathy continue, [ 60 ] [ 61 ]  with at least 100 cases identified in Brazil between 2005 and 2010. [ 62 ]  5.8 million thalidomide pills were distributed throughout Brazil in this time period, largely to poor Brazilians in areas with little access to healthcare, and these cases have occurred despite the controls. [ citation needed ]


In 1998, the FDA approved the drug's use in the treatment of ENL. [ 63 ]  Because of thalidomide's potential for causing birth defects, the drug may be distributed only under tightly controlled conditions. The FDA required that  Celgene Corporation , which planned to market thalidomide under the brand name  Thalomid , establish a system for thalidomide education and prescribing safety (STEPS) oversight program. The conditions required under the program include limiting prescription and dispensing rights to authorized prescribers and pharmacies only, keeping a registry of all patients prescribed thalidomide, providing extensive patient education about the risks associated with the drug, and providing periodic pregnancy tests for women who take the drug. [ 63 ]


In 2010, the  World Health Organization  stated that it did not recommend thalidomide for leprosy due to the difficulty of adequately controlling its use, and due to the availability of  clofazimine . [ 64 ]


Shortly after the teratogenic properties of thalidomide were recognized in the mid-1960s, its anti-cancer potential was explored and two clinical trials were conducted in people with advanced cancer, including some people with multiple myeloma; the trials were inconclusive. [ 65 ]


Little further work was done with thalidomide in cancer until the 1990s. [ 65 ]


Judah Folkman  pioneered studies into the role of  angiogenesis  (the proliferation and growth of blood vessels) in the development of cancer, and in the early 1970s had shown that  solid tumors  could not expand without it. [ 66 ] [ 67 ]  In 1993 he surprised the scientific world by hypothesizing the same was true of  blood cancers , [ 68 ]  and the next year he published work showing that a  biomarker  of angiogenesis was higher in all people with cancer, but especially high in people with blood cancers, and other evidence emerged as well. [ 69 ]   Meanwhile, a member of his lab, Robert D'Amato, who was looking for  angiogenesis inhibitors , discovered in 1994 that thalidomide inhibited angiogenesis [ 70 ]  and was effective in suppressing tumor growth in rabbits. [ 71 ]  Around that time, the wife of a man who was dying of multiple myeloma and whom standard treatments had failed, called Folkman asking him about his anti-angiogenesis ideas. [ 67 ]   Folkman persuaded the patient's doctor to try thalidomide, and that doctor conducted a clinical trial of thalidomide for people with multiple myeloma in which about a third of the subjects responded to the treatment. [ 67 ]   The results of that trial were published in the New England Journal of Medicine in 1999. [ 67 ] [ 72 ]


After further work was done by Celgene and others, in 2006 the US Food and Drug Administration granted accelerated approval for thalidomide in combination with dexamethasone for the treatment of newly diagnosed  multiple myeloma  patients. [ 67 ] [ 73 ]


It was also evaluated whether thalidomide can be combined with melphalan and prednisone for patients with multiple myeloma. This combination of drugs probably increases the overall survival. [ 74 ]


In the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities, such as  phocomelia , as a consequence of thalidomide use. [ 75 ]  The severity and location of the deformities depended on how many days into the pregnancy the mother was before beginning treatment, with the time-sensitive window occurring approximately between day 20 and day 36 post-fertilisation. [ 51 ]  Thalidomide taken on the 20th day of pregnancy caused central brain damage, day 21 would damage the eyes, day 22 the ears and face, day 24 the arms, and leg damage would occur if taken up to day 28. [ citation needed ]


It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000. [ 76 ]  Despite the side effects, thalidomide was sold in pharmacies in Canada until 1962. [ 57 ] [ 77 ]


The disaster prompted many countries to introduce tougher rules for the testing and licensing of drugs, such as the 1962  Kefauver Harris Amendment [ 85 ]   (US), 1965  Directive 65/65/EEC1  (EU), [ 86 ]  and the  Medicines Act 1968  (UK). [ 87 ] [ 88 ]  In the United States, the new regulations strengthened the FDA, among other ways, by requiring applicants to prove efficacy and to disclose all side effects encountered in testing. [ 75 ]  The FDA subsequently initiated the  Drug Efficacy Study Implementation  to reclassify drugs already on the market. [ citation needed ]


In 1977 the US Federal Drug Administration published a clinical trial guideline that excluded women of "childbearing potential" from the early phases of most clinical trials, which in practice led to their exclusion from later trial phases as well. [ 89 ]  This 1977 FDA guideline was implemented in response to a protectionist climate caused by the thalidomide tragedy. [ 89 ]  In the 1980s, a US task force on women's health concluded that a lack of women's health research (in part due to the FDA guideline) had compromised the amount and quality of information available about diseases and treatments affecting women. [ 89 ]  This led to the National Institute of Health policy that women should, when beneficial, be included in clinical trials. [ 89 ]


In the 1960s, thalidomide was successfully marketed as a safer alternative to  barbiturates . Due to a successful marketing campaign, thalidomide was widely used by pregnant women during the first trimester of pregnancy. However, thalidomide is a  teratogenic  substance, and a proportion of children born during the 1960s had thalidomide embryopathy (TE). [ 90 ]  Of these babies born with TE, "about 40% of them died before their first birthday". [ 91 ]  The surviving individuals are now middle-aged and they report experiencing challenges (physical, psychological, and socioeconomic) related to TE. [ citation needed ]


Individuals born with TE frequently experience a wide variety of health problems secondary to their TE. These health conditions include both physical and psychological conditions. When compared to individuals of similar demographic profiles, those born with TE report less satisfaction with their quality of life and their overall health. [ 90 ]  Access to healthcare services can also be a challenge for these people, and women, in particular, have experienced difficulty in locating healthcare professionals who can understand and embrace their needs. [ 91 ]


Brand names include Contergan, Thalomid, Talidex, Talizer, Neurosedyn, Distaval, and many others. [ 7 ]


Research efforts have been focused on determining how thalidomide causes birth defects and its other activities in the human body, efforts to develop safer analogs, and efforts to find further uses for thalidomide. [ citation needed ]


The exploration of the  antiangiogenic  and immunomodulatory activities of thalidomide has led to the study and creation of thalidomide  analogs . [ 92 ] [ 93 ]  Celgene has sponsored numerous clinical trials with analogues to thalidomide, such as  lenalidomide , that are substantially more powerful and have fewer side effects — except for greater  myelosuppression . [ 94 ]  In 2005, Celgene received FDA approval for  lenalidomide  (Revlimid) as the first commercially useful derivative. Revlimid is available only in a restricted distribution setting to avoid its use during pregnancy. Further studies are being conducted to find safer compounds with useful qualities. Another more potent analog,  pomalidomide , is now FDA-approved. [ 95 ]  Additionally,  apremilast  was approved by the FDA in March 2014. These  thalidomide analogs  can be used to treat different diseases, or used in a regimen to fight two conditions. [ 96 ]


Interest turned to  pomalidomide , a  derivative  of thalidomide marketed by  Celgene . It is a very active anti-angiogenic agent [ 93 ]   and also acts as an  immunomodulator . Pomalidomide was approved in February 2013 by the FDA as a treatment for relapsed and refractory  multiple myeloma . [ 97 ]  It received a similar approval from the  European Commission  in August 2013, and is expected to be marketed in Europe under the brand name  Imnovid . [ 98 ]


There is no conclusive evidence that thalidomide or  lenalidomide  is useful to bring about or maintain remission in Crohn's disease. [ 99 ] [ 100 ]


Thalidomide was studied in a Phase II trial for  Kaposi's sarcoma , a rare soft-tissue cancer most commonly seen in the immunocompromised, that is caused by the  Kaposi's sarcoma-associated herpesvirus  (KSHV). [ 101 ] [ 44 ]


Viedma ripening  or  attrition-enhanced deracemization  is a  chiral symmetry breaking  phenomenon observed in solid/liquid mixtures of enantiomorphous ( racemic conglomerate ) crystals that are subjected to  comminution . It can be classified in the wider area of  spontaneous symmetry breaking  phenomena observed in chemistry and physics.


It was discovered in 2005 by geologist Cristobal Viedma, who used glass beads and a magnetic stirrer to enable particle breakage of a racemic mixture of enantiomorphous  sodium chlorate  crystals in contact with their  saturated solution  in water. [ 1 ]  A  sigmoidal  ( autocatalytic ) increase in the solid-phase  enantiomeric excess  of the mixture was obtained, eventually leading to  homochirality , i.e. the complete disappearance of one of the  chiral  species. Since the original discovery, Viedma ripening has been observed in a variety of intrinsically chiral  organic compounds  that exhibit conglomerate  crystallization  and are able to inter-convert in the liquid via  racemization  reactions. [ 2 ]  It is also regarded as a potential new technique to separate  enantiomers  of chiral molecules in the pharmaceutical and fine chemical industries ( chiral resolution ).


The exact interplay of the mechanisms leading to deracemization in Viedma ripening is a subject of ongoing scientific debate. [ 3 ] [ 4 ]  It is, however, currently believed that for intrinsically chiral molecules, deracemization occurs via a combination of various phenomena:


Two key assumptions often invoked to explain the mechanism is that: a) small fragments generated by breakage for each enantiomeric crystal population can maintain their chirality, even when they are smaller than the  critical radius  for  nucleation  (and are thus expected to dissolve) and b) small chiral fragments can undergo enantiospecific aggregation to larger particles of the same chirality. Using these two assumptions, it can be shown mathematically, [ 6 ]  that any stochastic even immeasurable asymmetry of one enantiomeric crystal population over the other can be amplified to homochirality in a random manner.


In principle,  molecules  required for the generation of life, i.e.  amino acids  that combine to form  proteins  and  sugars  that form  DNA  molecules are all chiral and are thus able to adopt two mirror-image forms (often described as left- and right-handed), which from a chemical perspective are equally likely to exist. However, all biologically-relevant molecules known on earth are of a single handedness, even though their mirror images are also capable of forming similar molecules. The reason of the prevalence of  homochirality  in living organisms is currently unknown and is often connected to the  origin of life  itself. Whether homochirality emerged before or after life is currently unknown, but many researchers believe that homochirality could have been a result of amplification of extremely small chiral asymmetries.


Since Viedma ripening has been observed in biologically-relevant molecules, such as chiral amino acids [ 7 ]  it has been put forward by some as a possible contributing mechanism for chiral amplification in a prebiotic world. [ 8 ] [ 9 ] [ 10 ]


When Topology Meets Chemistry: A Topological Look At Molecular Chirality  is a book in  chemical graph theory  on the graph-theoretic analysis of  chirality  in molecular structures. It was written by  Erica Flapan , based on a series of lectures she gave in 1996 at the  Institut Henri Poincaré , [ 1 ]  and was published in 2000 by the  Cambridge University Press  and  Mathematical Association of America  as the first volume in their shared Outlooks book series. [ 2 ]


A chiral molecule is a molecular structure that is different from its mirror image. This property, while seemingly abstract, can have big consequences in biochemistry, where the shape of molecules is essential to their chemical function, [ 3 ]  and where a chiral molecule can have very different biological activities from its mirror-image molecule. [ 4 ]   When Topology Meets Chemistry  concerns the mathematical analysis of molecular chirality.


The book has seven chapters, beginning with an introductory overview and ending with a chapter on the chirality of  DNA  molecules. [ 2 ]
Other topics covered through the book include the rigid geometric chirality of tree-like molecular structures such as  tartaric acid , and the stronger topological chirality of molecules that cannot be deformed into their mirror image without breaking and re-forming some of their molecular bonds. It discusses results of Flapan and Jonathan Simon on molecules with the molecular structure of  Möbius ladders , according to which every embedding of a Möbius ladder with an odd number of rungs is chiral while Möbius ladders with an even number of rungs have achiral embeddings. It uses the symmetries of graphs, in a result that the symmetries of certain graphs can always be extended to topological symmetries of three-dimensional space, from which it follows that  non-planar graphs  with no  self-inverse symmetry  are always chiral. It discusses graphs for which  every embedding is topologically knotted or linked . And it includes material on the use of  knot invariants  to detect topological chirality. [ 1 ] [ 2 ] [ 4 ] [ 5 ]


The book is self-contained, and requires only an undergraduate level of mathematics. [ 3 ] [ 5 ]  It includes many exercises, [ 2 ]  making it suitable for use as a textbook at both the advanced undergraduate and introductory graduate levels. [ 1 ]  Reviewer Buks van Rensburg describes the book's presentation as "efficient and intuitive", and recommends the book to "every mathematician or chemist interested in the notions of chirality and symmetry". [ 6 ]


In  physics ,  zilch  (or zilches) is a set of ten  conserved quantities  of the source-free  electromagnetic field , which were discovered by Daniel M. Lipkin in 1964. [ 1 ]  The name refers to the fact that the zilches are only conserved in regions free of  electric charge , and therefore have limited physical significance. One of the conserved quantities (Lipkin's

 Z

 0

 {\displaystyle Z^{0}}

 ) has an intuitive physical interpretation and is also known as  optical chirality .


In particular, first, Lipkin observed that if he defined the quantities


The free  Maxwell equations  imply that

 ∂

 0

 Z

 0

 +
 ∇
 ⋅

 Z

 =
 0

 {\displaystyle \partial _{0}Z^{0}+\nabla \cdot \mathbf {Z} =0}

 .


The precedent equation implies that the quantity

 ∫

 Z

 0

 d

 3

 x

 {\displaystyle \int Z^{0}\,d^{3}x}

  is constant. This time-independent quantity is one of the ten zilches discovered by Lipkin. Nowadays, the quantity

 ∫

 Z

 0

 d

 3

 x

 {\displaystyle \int Z^{0}\,d^{3}x}

  is widely known as  optical chirality  (up to a factor of 1/2). [ 2 ]


The quantity

 Z

 0

 {\displaystyle {Z}^{0}}

  is the  spatial density  of optical chirality, while

 Z

 {\displaystyle \mathbf {Z} }

  is the  optical chirality flux . [ 2 ]  Generalizing the aforementioned differential conservation law for

 Z

 0

 {\displaystyle Z^{0}}

 , Lipkin found other nine conservation laws, all unrelated to the  stress–energy tensor . He collectively named these ten conserved quantities the zilch (nowadays, they are also called the zilches [ 3 ] ) because of the apparent lack of physical significance. [ 1 ] [ 4 ]


The zilch is often described in terms of the zilch tensor,

 Z

 ν
 ρ

 μ

 {\displaystyle Z_{\nu \rho }^{\mu }}

 . The latter can be expressed using the  dual   electromagnetic tensor

 F
 ^

 μ
 ν

 =
 (
 1

 /

 2
 )

 ϵ

 μ
 ν
 ρ
 σ

 F

 ρ
 σ

 {\displaystyle {\hat {F}}^{\mu \nu }=(1/2)\epsilon ^{\mu \nu \rho \sigma }F_{\rho \sigma }}

  as

 Z

 ν
 ρ

 μ

 =

 F
 ^

 μ
 λ

 F

 λ
 ν
 ,
 ρ

 −

 F

 μ
 λ

 F
 ^

 λ
 ν
 ,
 ρ

 {\displaystyle Z_{\nu \rho }^{\mu }={\hat {F}}^{\mu \lambda }F_{\lambda \nu ,\rho }-F^{\mu \lambda }{\hat {F}}_{\lambda \nu ,\rho }}

 . [ 5 ]


The zilch tensor is symmetric under the exchange of its first two  indices ,

 μ

 {\displaystyle \mu }

  and

 ν

 {\displaystyle \nu }

 , while it is also  traceless  with respect to any two indices, as well as  divergence-free  with respect to any index. [ 5 ]


The conservation law

 ∂

 ρ

 Z

 μ
 ν
 ρ

 =
 0

 {\displaystyle \partial _{\rho }Z^{\mu \nu \rho }=0}

  means that the following ten quantities are time-independent:


It was later demonstrated that Lipkin's zilch is part of an infinite number of zilch-like conserved quantities, a general property of free  fields . [ 5 ]


One of the zilches has been rediscovered. This is the zilch called "optical chirality", named by Tang and Cohen, since this zilch determines the degree of chiral asymmetry in the rate of excitation of a small chiral molecule by an incident electromagnetic field. [ 2 ]
A further physical insight of optical chirality was offered in 2012; optical chirality is to the curl or time derivative of the electromagnetic field, what helicity, spin and related quantities are to the electromagnetic field itself. [ 6 ]
The physical interpretation of all zilches for topologically non-trivial electromagnetic fields was investigated in 2018. [ 3 ]


Since the discovery of the ten zilches in 1964, there is an important open mathematical question concerning their relation with symmetries. (Recently, the full answer to this question seems to have been found  [ 7 ] ). This is the question:


What are the symmetries of the standard Maxwell action functional:


S
 [

 A

 μ

 ]
 =
 −

 1
 4

 ∫

 d

 4

 x

 F

 μ
 ν

 F

 μ
 ν

 {\displaystyle S[A_{\mu }]=-{\frac {1}{4}}\int d^{4}xF_{\mu \nu }F^{\mu \nu }}


(with

 F

 μ
 ν

 =

 ∂

 μ

 A

 ν

 −

 ∂

 ν

 A

 μ

 {\displaystyle F_{\mu \nu }=\partial _{\mu }A_{\nu }-\partial _{\nu }A_{\mu }}

  and

 A

 μ

 {\displaystyle A_{\mu }}

  is the dynamical field variable) that give rise to the conservation of all zilches using  Noether's theorem . Until recently, the answer to this question had been given only for the case of optical chirality by Philbin in 2013. [ 8 ]
This open question was also emphasized by Aghapour, Andersson and Rosquist in 2020, [ 9 ]
while these authors found the symmetries of the duality-symmetric Maxwell action underlying the conservation of all zilches. (Aghapour, Andersson and Rosquist did not find the symmetries of the standard Maxwell action, but they speculated that such symmetries should exist  [ 9 ] ).
There are also earlier works studying the conservation of zilch in the context of duality-symmetric electromagnetism, [ 10 ]  but the variational character of the corresponding symmetries was not established.


The full answer to the aforementioned question seems to have been given for the first time in 2022, [ 7 ]  where the symmetries of the standard Maxwell action underlying the conservation of all zilches were found. According to this work, there is a hidden invariance algebra of free Maxwell equations in potential form that is related to the conservation of all zilches.


The  Alcohol and Drugs History Society  ( ADHS ) is a scholarly organization whose members study the history of a variety of illegal, regulated, and unregulated  drugs  such as  opium ,  alcohol , and  coffee . Organized in 2004, the ADHS is the successor to a society with a more limited scope, the Alcohol and Temperance History Group, which existed for 25 years. The last ATHG president and the first ADHS president was Ian R. Tyrrell, Professor of History at the University of New South Wales, in Australia.  In July 2006 he was succeeded by  W.J. Rorabaugh , Professor of History at the University of Washington.  In July, 2008, David T. Courtwright, Professor of History at the  University of North Florida  became president.  In 2011 Joseph Spillane, Associate Professor of History at the University of Florida, succeeded him as president.


The ADHS sponsors the academic journal  The Social History of Alcohol and Drugs: an Interdisciplinary Journal  (SHAD). The journal appears in both printed and electronic formats, published twice a year, in the winter and the summer. Starting in 2019, the journal was published by the University of Chicago Press. SHAD's editorial structure recently [ when? ]  changed and its current co-editors are David Herzberg (SUNY-Buffalo), Nancy Campbell (Rensselaer Polytechnic Institute), and Lucas Richert (University of Strathclyde). Its former editor-in-chief is Dan Malleck, from  Brock University ,  St. Catharines ,  Canada . Other former editors include Jim Mills, from  University of Strathclyde  in  Glasgow ,  Scotland ; W. Scott Haine, from  California , and the Reviews Editors are James Nicholls, from  Bath Spa University ,  England  and Alex Mold, from the London School of Hygiene and Tropical Medicine.  In November, 2009 it created an editorial board, which is populated by some of the most prominent alcohol and drugs history scholars in the world.


The ADHS is affiliated with the  American Historical Association  and sponsors sessions at the January meetings of the AHA.


The ADHS held an international conference in  Canada  in August 2007, with  Guelph University  (Ontario) as the host  The next international conference was in  2009 at  Glasgow ,  Scotland , with the  University of Strathclyde  as the host.  In 2011 an international conference was held at the State University of New York, Buffalo. In 2015 the ADHS met at Bowling Green State University in Ohio, USA. In 2017 there was an international conference at the University of Utrecht, The Netherlands. Shanghai will serve as host for the 2019 meeting.


The  American College of Clinical Pharmacology®  ( ACCP ) is a national organization of  clinical pharmacology  healthcare professionals who seek to advance clinical pharmacology. [ 1 ]


In the 1960s, a group of physicians formulated the concept of an organization dedicated to a new branch of pharmacology that dealt with the effectiveness and safety of drugs in humans. As a result of their efforts, the American College of Clinical Pharmacology (ACCP) was founded on September 11, 1969. [ 2 ]


The mission is to improve health by optimizing  therapeutics  and to provide leadership and education that enables the generation, integration and translation of scientific knowledge to optimize research, development and utilization of medication. [ 3 ]


ACCP is governed by a  Board of Regents  elected by ACCP Members. The Board is advised by a network of ACCP committees. [ 1 ]


Levels of membership in ACCP are Retired, Student, Member and Fellow (FCP).  Fellowship  is the organization's way of noting outstanding achievement in the discipline. Fellows require specific credentials and are recommended by their peers and reviewed by the Board of Regents. [ 1 ]


The Journal of Clinical Pharmacology , published by ACCP is the main journal of the College.  Clinical Pharmacology in Drug Development  is another publication. [ 1 ]


The College organizes a number of annual meetings and has several committees. There are special programs for students and to promote the discipline in developing countries. [ 1 ]


ACCP promotes the rational use of medications in humans through research, development and regulation of medications, and education of healthcare professionals and patients on the optimal utilization of medications. [ 1 ]


ACCP is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. [ 4 ]


The  American Society for Pharmacology and Experimental Therapeutics  (ASPET) is a scientific society founded in late 1908 by  John Jacob Abel  of  Johns Hopkins University  (also the founder of the  American Society for Biochemistry and Molecular Biology ), with the aim of promoting the growth of pharmacological research. [ 1 ] [ 2 ]  Many society members are researchers in basic and clinical pharmacology who help develop disease-fighting medications and therapeutics. [ 3 ]  ASPET is one of the constituent societies of the  Federation of American Societies for Experimental Biology  (FASEB). [ 4 ]  The society's headquarters are in  Rockville, MD . The current president is Michael F. Jarvis. [ 5 ]


The society publishes three research journals and a review journal: the  Journal of Pharmacology and Experimental Therapeutics ,  Drug Metabolism and Disposition ,  Molecular Pharmacology , and  Pharmacological Reviews


Starting in 2012 these publications are only offered online. The society copublishes a wholly open access journal with the British Pharmacological Society and Wiley entitled  Pharmacology Research & Perspectives .


ASPET also publishes a quarterly newsletter,  The Pharmacologist , and, from 2001 to 2011,  Molecular Interventions  magazine.


The society gives out several awards: [ 6 ]


Travel awards to participate in its meetings are also given to students and postdocs. [ 7 ]


The  Association for Ocular Pharmacology and Therapeutics  ( AOPT ) is an organization that welcomes members from disciplines related to ocular pharmacology and its therapeutic applications. The mission of AOPT is the sustenance of a scientific network aiming the dissemination of knowledge in the field of  ocular disease ,  pharmacology  and  therapeutics .


AOPT was begun informally in the 1970s by Dr. George Chiou [ 1 ] [ 2 ]  as special sessions at the Federation of American Societies for Experimental Biology [ 3 ]  conferences. It grew to an official separate Symposium of Ocular Pharmacology meeting of academicians, clinicians, and pharmaceutical industry at Novi, Michigan in August 1993. [ 4 ]  The participants voted to charter the organization and this was accomplished the next year with the first AOPT meeting held in New Orleans, Louisiana in January 1995. The founding board comprised Drs. George Chiou (president), David Lee (vice-president), Hitoshi Shichi (treasurer), and Herbert Kaufman (trustee). During the early FASEB years, Chiou also established the  Journal of Ocular Pharmacology , now the  Journal of Ocular Pharmacology & Therapeutics . The history of AOPT is closely related to the Association for Research in Vision and Ophthalmology (ARVO). [ 5 ]


The mission of AOPT is to help researchers and eye-care professionals in their efforts toward the understanding and the treatment of eye diseases. AOPT scientific dissemination involves preclinical and clinical pharmacologists and researchers. Scientific dissemination is promoted through biennial meetings  [ 6 ]  and the  peer-reviewed journal :  Journal of Ocular Pharmacology and Therapeutics  ( JOPT ).


JOPT  is the official journal of AOPT. It is a multidisciplinary journal that covers the latest findings related to  pharmacodynamics  and  pharmacokinetics  of pharmaceuticals used in the treatment of ocular disorders. [ 7 ]   The journal is published 10 times per year.  This journal is peer reviewed with on line access prior to journal publication and it is available in 170 countries ( http://home.libertpub.com ).  The journal also publishes Special Issues.  The next one is "N ext Generation Tissue Engineering:  Inspired Models for Ophthalmic Drug Discovery ".  (Ashwath Jayagopal and Héloïse Ragelle guest editors.  The current editor-in-chief of JOPT is  W. Daniel Stamer, PhD .(Duke University, Durham, NC  http://medschoolduke.edu/about-us/our-faculty/w-daniel-stamer  ) On line ISSN 1557-7732 with an impact factor of 1.782.  Affiliated with AOPT and ISOPT  Clinical  ( International Symposium on Ocular Pharmacology & Therapeutics Clinical) ( http://isopclinical.com )


AOPT has a diverse leadership and membership which include principal investigators, scientists, medical professionals, technicians, and students with an interest in ocular pharmacology and therapeutics. The directive committee and members come from academic institutions and private companies worldwide.


Members of AOPT and societies in the field of eye research, gather every year at the annual  ARVO  meeting, in which the latest findings in vision and ophthalmology research are disseminated.
Societies in the field of eye research span from preclinical to clinical and a few of these societies are hereby listed:


The  British Pharmacological Society  is the primary UK  learned society  for  pharmacologists , concerned with research into drugs and the ways in which they work. Members work in academia, industry, regulatory agencies, and the health services, and many are medically qualified. The Society covers the whole spectrum of pharmacology, including laboratory, clinical, and toxicological aspects. [ 1 ]


Clinical pharmacology is the medical speciality dedicated to promoting safe and effective use of medicines for patient benefit. Many  clinical pharmacologists  work as consultants in the  National Health Service  and many hold prominent positions in UK universities and in regulatory bodies, such as the Medicines and Healthcare products Regulatory Agency (MHRA) and the  National Institute of Health and Care Excellence  (NICE). [ 2 ]


The Society was founded in 1931, in Oxford, by a group of about 20 pharmacologists. [ 3 ]  They were brought together on the initiative of  Professor James Andrew Gunn , through a letter signed by Gunn,  Henry H. Dale , and  Walter E. Dixon , and sent to the heads of university departments of pharmacology and of institutions for pharmacological research in Great Britain, with proposals for the formation of a pharmacological club. There were favorable replies to this letter, and most of the recipients met in  Wadham College , Oxford, on the evening of 3 July 1931, the day before the meeting of the  Physiological Society . Gunn presided over the meeting. It was agreed that a Society should be founded, to meet at least once a year for the reading of papers on pharmacological subjects and discussions of questions of teaching and publications and to promote friendly relations between pharmacologists. [ 4 ] [ 5 ]


The first female member of the society was  Mary Pickford  (1935), and other early eminent women members included  Marthe Vogt  and  Edith Bülbring . [ 6 ]


The British Pharmacological Society publishes several works that promote pharmacology and clinical pharmacology:


The office of president was formally created in 1999. Before that the role was taken by members of the society under titles such as secretary and general secretary. Since 2010, all previous general secretaries and presidents have been awarded the title  president emeritus .


Secretary and treasurer


Secretary


General secretary


President


The society elects eminent, deceased contributors to the subject of pharmacology, whether or not they were members, to the Pharmacology Hall of Fame: [ 12 ]


Members of the society awarded the  Nobel Prize in Physiology or Medicine  include Black, Dale and Vane. [ citation needed ]


Fellowships (FBPhS) of the society are awarded to members who have made significant contributions to both the study of pharmacology and the Society. [ 15 ]  A full list of Fellows is available here. [ 16 ]  Honorary Fellowships (HonFBPhS) are awarded to member or non-members for distinguished and sustained leadership role in Pharmacology. Fellows and Honorary Fellows use the post-nominal FBPhS. Notable current honorary fellows include:


The Canadian Society for Pharmaceutical Research (CSPS) advocates for excellence in pharmaceutical research, promotes the allocation of research funds, seeks involvement in decision and policy making processes and provides a forum for early scientists. It was founded in 1997. The  Journal of Pharmacy and Pharmaceutical Sciences . [ 1 ] [ 2 ]  is the official journal of CSPS.


The  Canadian Society of Pharmacology and Therapeutics  (CSPT;  French :  Société Canadienne de Pharmacologie et de Thérapeutique ) is an academic association whose mission is the promotion of research and education in  pharmacology  and  therapeutics  in Canada.  It  comprises graduate students, postdoctoral fellows, established investigators and clinical scientists working in academia, clinical practice, government, and industry.  Despite being based in Canada and having a majority of Canadian members, this is not a condition of membership, and the Society has members from all over the world. The CSPT is the Canadian member of the  International Union of Basic and Clinical Pharmacology .


The  European Association for Clinical Pharmacology and Therapeutics  (EACPT) is a  learned society  in the field of  clinical pharmacology . It is the leading society in Europe serving the European and global Clinical Pharmacology and Therapeutics community. It has its origins in a working party in the early 1980s under the auspices of the  World Health Organization  (WHO-Europe). Subsequently, a committee was created in 1993 chaired by Folke Sjöqvist [ 1 ]  with the remit to prepare the first congress of EACPT, held in Paris in 1995. [ 2 ]  At that congress the founding EACPT Council elected an Executive Committee with Sjöqvist as chairman, Michael Orme (United Kingdom) as Honorary Secretary, Jochen Kuhlmann (Germany) as Treasurer, and Giampaolo Velo (Italy) as Vice-Chairman, with 26 European countries as members through their home country clinical pharmacology society or section. [ 3 ]  The EACPT now includes all national organisations for clinical pharmacology in Europe and provides educational and scientific support for the more than 4000 individual professionals interested in Clinical Pharmacology and Therapeutics throughout the European region, with its congresses attended by a global audience.


The EACPT promotes in Europe professional and ethical excellence and standards for clinical use of medicines and clinical research on drugs. The EACPT also aims to advise policy makers on how the specialty can contribute to human health and wealth. [ 4 ]


Activities of the EACPT include advice to policy makers and agencies in Europe, holding European congresses and workshops, and publishing policy papers, meeting reports, proceedings of congresses and constituent symposia, and contents of specific lectures. [ 5 ] [ 6 ]  The EACPT also holds Focus Meetings. [ 7 ]


Source: [ 10 ]


Congresses [ 11 ]  are open to delegates from Europe and anywhere in the world, including health professionals, researchers, biotechnology and pharmaceutical industry professionals, regulators, policy makers, ethicists and others interested in drug discovery, and in clinical, cost-effectiveness and safety of medicines and related biomarkers.


The EACPT is led by an Executive Committee [ 22 ]  formed from a council of delegates from affiliated national societies [ 23 ]  for clinical pharmacology and  therapeutics . The EACPT also has key Working Groups for Research, Ethics and Regulatory Matters, Education and Young Pharmacologists. [ 24 ]


Clinical Therapeutics [ 25 ]


The  European College of Neuropsychopharmacology  ( ECNP ) is a pan-European,  non-profit  scientific association that serves as a platform to exchange and promote research in the field of  neuropsychopharmacology . The ECNP “is committed to ensuring that advances in the understanding of brain function and human behaviour are translated into better treatments and enhanced public health”. [ 1 ]  The ECNP organises a number of activities to achieve this aim, such as a yearly congress, workshops, seminars, New Frontiers Meetings, publications ,  awards, supported talks and much more.


In 1984 representatives of neuropsychopharmacological societies from across Europe suggested there might be room for a European structure. A meeting to discuss this plan further was held in Copenhagen in May 1985. It was decided that a European College of Neuropsychopharmacology would be founded. A Working Group was formed to plan of the association’s inaugural scientific congress. This congress was held in Brussels in 1987. Around 500 people attended. [ 2 ]
The Working Group consisted of: [ 3 ]


In 1993 the College established a permanent secretariat in  Utrecht ,  Netherlands . [ 2 ]


The ECNP’s executive organ is the Executive Committee. The Executive Committee consists of six officers (the president, vice- president, president-elect, past-president, secretary and treasurer) and a maximum of six councillors. The Executive Committee has a three year term. [ 4 ]


The  2019-2022 Executive Committee  consists of: [ 5 ]


Martien Kas ,  The Netherlands , President
 Gitte Moos Knudsen ,  Denmark , Past-President
 Andreas Reif ,  Germany , President-Elect
 Elisabeth Binder ,  Germany , Vice-President
 Catherine Harmer ,  United Kingdom , treasurer
 Suzanne Dickson ,  Sweden , Secretary


Councillors
 David Baldwin ,  United Kingdom
 Paolo Brambilla ,  Italy
 Iria Grande ,  Spain
 Iiris Hovatta ,  Finland
Marin Jukic,  Sweden
 Marion Leboyer ,  France


Chair Scientific Programme Committee
John Cryan,  Ireland


Editor-in-chief  European Neuropsychopharmacology   ENP
 Eduard Vieta ,  Spain


Editor-in-chief  Neuroscience Applied
 Andreas Meyer-Lindenberg ,  Germany


Executive Director
Alexander Schubert,  The Netherlands


Past presidents are: [ 6 ]


Gitte Moos Knudsen ,  Denmark  (2019-2022)
 Celso Arango ,  Spain  (2016-2019)
 Guy Goodwin ,  United Kingdom  (2013-2016)
 Joseph Zohar ,  Israel  (2010-2013)
 David Nutt ,  United Kingdom  (2007-2010)
Julien Mendlewicz,  Belgium  (2004-2007)
Yves Lecrubier,  France  (2002-2004)
Jan M. van Ree,  Netherlands  (1998-2002)
Manfred Ackenheil,  Germany  (1995-1998)
Stuart A. Montgomery,  United Kingdom  (1992-1995)
Salomon Z. Langer,  France  (1989-1992)
Carl-Gerhard Gottfries,  Sweden  (1987-1989)


The Executive Committee oversees the work of various sub-committees of the Executive Committees. These committees are staffed by scientists working in the field of  neuropsychopharmacology . [ 7 ]


Abstract and Poster Committee


The Abstract and Poster Committee oversees the abstract and poster process of the ECNP Congress.


Award Committee


The Award Committee reviews applications for the ECNP Neuropsychopharmacology Award. The terms and criteria for this award, however, are set by the Executive Committee.


Early Career Advisory Panel (ECAP)


Six years ago ECNP founded the Early Career Advisory Panel (ECAP) to advise on the needs of future members of the College, to give input on development of Early Career Scientist activities and initiatives, to help generate activities for Early Career Scientists and clinicians, and to receive feedback on current activities.


Educational Committee


The Educational Committee is charged with propagating best practices in European applied neuroscience, from research methods and to clinical standards. As such, it oversees ECNP’s training activities and educational programmes, especially for early career scientists.


Networks Board and Taskforce


Each ECNP Network is led by a Chair and a Co-chair. Chairs and Co-chairs of Networks and thematic working groups (TWGs) form the Networks Taskforce, which reports to the Networks Board and meets twice a year. The Networks Board guides the ECNP Networks.


New Frontiers Programme Committee


The committee is responsible for developing the programme of the New Frontiers Meeting, held annually in Nice, France, and for guiding the ongoing discussion the meeting is designed to stimulate.


Workshop Committee


The Workshop Committee is charged with the organisation of the ECNP Workshop on Neuropsychopharmacology for Early Career Scientists in Europe, held annually in Nice, France.


External Review Board of the ECNP


The External Review Board of the ECNP (formerly known as the Scientific Committee) was established in 2007 with the broad aim of overseeing the quality assurance of ECNP’s governance and that of its activities.
 Nominating Committee


The Nominating Committee nominates candidates for the future Executive Committee (EC).


Scientific Advisory Panel


The Scientific Advisory Panel (SAP) is ECNP’s scientific sounding board, providing guidance and content advice in ECNP’s key areas of scientific focus in disorders, interventions and methods.


Scientific Programme Committee (ECNP Congress)


The chair of the Scientific Programme Committee (SPC) is appointed by the Executive Committee for three consecutive ECNP Congresses. For each congress, the chair SPC submits a proposal of committee members to the Executive Committee for approval, taking into account scientific standing of potential candidates, as well as the overall geographical and disciplinary balance. The independent SPC is charged with ensuring that the programme is of a uniformly high standard and balanced across the field of applied and translational neuroscience.


ECNP Workshop


ECNP Workshop on Clinical Research Methods


This Workshop aims at introducing early career clinicians (psychiatrists, clinical psychologists, etc) into research methodology and to promote a critical thinking approach to the scientific literature that is particularly relevant to clinical practice.


ECNP New Frontiers Meeting


ECNP Negative Results Prize in Clinical Neuroscience


The ECNP Negative Results Prize in Clinical Neuroscience recognises those who have made exceptional contributions to CNS treatment development by publishing clinical research with negative findings.


Best Negative Data Prize


The Best Negative Data Prize is a collaboration between ECNP and U.S.-based non-profit research organisation Cohen Veterans Bioscience to recognise published “negative” scientific results or results of studies that do not confirm the expected outcome or original hypothesis.


ECNP Citation Prize


The ECNP Citation Prize recognises and encourage impactful original research in the ECNP journal,  European Neuropsychopharmacology (ENP) . It is awarded to the most cited research paper in the preceding two years.


ECNP Neuropsychopharmacology Award


The ECNP Neuropsychopharmacology Award recognises exceptional research achievements in applied and translational neuroscience.


ECNP Poster Award


Outstanding posters presented at the congress are awarded the ECNP Poster Award.


ECNP Public Choice Poster Award


The best poster presented at the congress that is chosen by the public is awarded the ECNP Public Choice Poster Award.


ECNP Seminar Award


ECNP confers two awards during each ECNP Seminar to help and encourage the most promising ECNP Seminar participants to visit the upcoming ECNP Congress.


ECNP Excellence Award


The ECNP Excellence Award was established to encourage Early Career Scientists (ECS) resident in Europe and/or residents of a European Country with a Developing Country (CDE) to present a poster during the annual ECNP Congress.


ECNP Rising Star Award


The ECNP Rising Star Award honours an Early Career Scientist whose research in applied and translational neuroscience has the potential to advance the science and treatment and prevention of brain disorders.


The ECNP publishes:


Alliance for Biomedical Research in Europe


Alliance for Biomedical Research
 European Brain Council  (EBC) (founder member)
 Federation of European Neuroscience Societies  (FENS) (founder member)
 International Society for CNS Clinical Trials and Methodology  (ISCTM)


The  Federation of European Pharmacological Societies  (EPHAR) [ 1 ]  is a non-profit voluntary association established to advance research and education in the science of  pharmacology  and to promote co-operation between national/regional pharmacological societies in  Europe  and surrounding countries. It is an  umbrella organization  of currently 29 national societies for pharmacology and represents over 12,000 individual pharmacologists in Europe. Moreover it seeks to co-operate with other international organizations, especially the  International Union of Basic and Clinical Pharmacology  (IUPHAR) of which EPHAR is an associate member. [ 2 ]


The efforts in the 1990s to unite European economical and political forces had found their counterpart in formation of European scientific federations. One of those scientific federations is EPHAR that was founded at the XIth International Congress of Pharmacology in  Amsterdam  (The Netherlands) in 1990. The establishment of the federation was prepared by a steering committee formed in 1988 under the initiative of Rodolfo Paoletti. The steering committee, headed by Börje Uvnäs, consisted of six members: Alasdair Breckenridge (UK), Flaminio Cattabeni (Italy), Gilles Fillion (France), Ove A. Nedergaard (Denmark), Rodolfo Paoletti (Italy), Hasso Scholz (Germany), Börje Uvnäs (Sweden). EPHAR was recognized as an affiliate member of IUPHAR in 1994. Since 1990, the Federation has sponsored important scientific events. In particular, EPHAR has contributed in the organization of residential courses with a restricted number of participants ("Molecular Biology in Pharmacology", Milan, 1990; "Neuroimmunomodulation in Pharmacology", Paris, 1992; "Electrophysiology in Pharmacology", London, 1993). [ 3 ]


Pharmacology has developed into a multifaceted discipline extending from  molecular biology  at the one end to  clinical pharmacology  at the other. [ 4 ]  The necessity of collaborative efforts within all branches of  biological sciences , in the development and analysis of new  drugs , is the driving force of the activities of EPHAR. One challenge of this federation is the creation of new generations of pharmacologists with an analytical and broadminded attitude towards important aspects of modern medical biological sciences. [ 5 ]


The Federation seeks to achieve its objects by arranging instructional courses and training programs in matters connected with pharmacology, facilitating the exchange of scientific information between European pharmacologists (by encouraging the holding of joint meetings between European member societies), disseminating information and encouraging the participation to important activities organized by member societies. This will include the production of a calendar of the National and joint meetings of each European Society.


Another important goal of the Federation is establishing common standards for basic courses in pharmacology, and fixing minimal standards for a European Pharmacologist Certificate.


The scientific dissemination is a fundamental step in progress and advance in research and education. For this reason, the most important scientific events established by the Federation are the EPHAR Congresses. They include plenary lectures, symposia, round tables, oral and poster communications devoted to the most recent advances in pharmacology and related sciences and therefore represented the adequate forum for discussing preclinical, clinical and therapeutic data. Particular emphasis was given to the impact of  biotechnologies  on  drug development  and to the identification of novel pharmacological approaches to  incurable   diseases . Sessions were also held on drug development, strategies for  research funding  and training of pharmacologists.


The EPHAR Congresses that have taken place since EPHAR’s foundation are: [ 5 ]


EPHAR supports activities, organized by its member societies that are intended to improve the cooperation among European pharmacologists. They are traditionally


One of these activities per year, for each country, is promoted by EPHAR. Calls for applications for these EPHAR-supported activities and the guidelines for these events are announced annually.


Moreover EPHAR gives prizes to European young investigators in the field of pharmacology, the EPHAR Young Investigators Awards. So far, the following awards were given:


The term of the EPHAR Executive Committees is four years.


The present (2022–2026) Executive Committee is composed by the following members: [ 6 ]


Past Presidents were:


The National Societies members of EPHAR are (in alphabetical order):
•	Austrian Pharmacological Society (Österreichische Pharmakologische Gesellschaft) APHAR.
•	Belgian Society of Fundamental and Clinical Physiology and Pharmacology. Société Belge de Physiologie et de Pharmacologie Fondamentales et Cliniques. Belgisch Genootschap voor Fundamentele en Klinische Fysiologie en Farmacologie.
•	Association of Pharmacologists of the Federation of Bosnia and Herzegovina. Udruženje Farmakologa Federacije Bosne i Hercegovine.
•	 British Pharmacological Society  (BPS).
•	Bulgarian Pharmacological Society.
•	Croatian Pharmacological Society. Hrvatsko Društvo Farmakologa. (HDF).
•	Czech Society for Experimental and Clinical Pharmacology and Toxicology. Česká Společnost pro Experimentální a Klinickou Farmakologii a Toxicologii (ČSEKFT).
•	Danish Society for Pharmacology, Toxicology and Medicinal Chemistry. Dansk Selskab for Farmakologi, Toksikologi og Medicinalkemi (DSFTM).
•	Dutch Pharmacological Society. Nederlands Vereniging voor Farmacologie (NVF)
•	Finnish Pharmacological Society. Suomen Farmakologiyhdistys. (SFY).
•	French Society of Pharmacology and Therapeutics. Société Française de Pharmacologie et de Thérapeutique. (SFPT).
•	German Society of Pharmacology. Deutsche Gesellschaft für Pharmakologie. (DGP).
•	Hellenic (Greek) Society of Basic and Clinical Pharmacology. Ελληνική Εταιρεία Φαρμακαλογίας (Ellinikí Etaireía Pharmakologías).
•	Hungarian Society for Experimental and Clinical Pharmacology. Magyar Kisérletes és Klinikai Farmakólogiai Társaság (MFT).
•	Israel Society for Physiology and Pharmacology (ISPP).
•	Società Italiana di Farmacologia (SIF).
•	Latvian Society of Pharmacology. Latvijas Farmakoloģijas biedrība. (LFB).
•	Norwegian Society for Pharmacology and Toxicology. Norsk Selskap for Farmakologi og Toksikologi. (NSFT).
•	Pharmacology Society of Malta.
•	Polish Pharmacological Society. Polskie Towarzystwo Farmakologiczne. (PTST).
•	Portuguese Pharmacological Society. Sociedade Portuguesa de Farmacologia (SPF).
•	Russian Scientific Society of Pharmacology.
•	Serbian Pharmacological Society. Српско Фармаколошко Друштво / Srpsko Farmakološko Društvo (СФД / SFD).
•	Slovak Pharmacological Society. Slovenská Farmakologická Spoločnosť (SFaS).
•	Slovenian Pharmacological Society. Slovensko Društvo Farmakologov. (SDF).
•	Spanish Society of Pharmacology. Sociedad Española de Farmacología (SEF).
•	Swedish Society for Pharmacology, Clinical Pharmacology and Therapeutics. Sektionen för Läkemedelslära.
•	Swiss Society of Pharmacology and Toxicology. Société Suisse de Pharmacologie et de Toxicologie/ Schweizerische Gesellschaft für Pharmakologie und Toxikologie (SSPT/SGPT).
•	 Turkish Pharmacological Society. Türk Farmakoloji Derneği  (TFD).


EPHAR website:  http://www.ephar.org/


The internet sites for each European pharmacological society, member of EPHAR, are hereby listed:


•	Austria:  http://www.aphar.at/


•	Belgium:  http://users.ugent.be/~jvdvoord/physiology&pharmacology/index.htm


•	Croatia:  http://pharma.mef.hr/


• 	Czech Republic:  http://farmspol.cls.cz/


•	Denmark  https://web.archive.org/web/20130903234249/http://dsftm.dk/index.php/en/


•	Netherlands:  http://www.nvfarmaco.nl/


•	Finland:  http://www.sfy.fi/


•	France:  http://www.pharmacol-fr.org/


•	Germany:  http://www.dg-pharmakologie.de/


•	Greece:  https://web.archive.org/web/20131007085419/http://gsp.med.auth.gr/


•	Hungary:  http://www.mapharm.hu/


•	Italy:  http://www.sifweb.org/


•	Norway:  http://www.nsft.net/   Archived  2014-12-18 at the  Wayback Machine


•	Poland:  http://www.ptf.info.pl/


•	Serbia:  http://www.sfarmd.org/


•	Slovakia:  http://www.sfarm.sk/


•	Spain:  http://www.socesfar.com/


•	Sweden  http://www.lakemedelslara.se/


•	Switzerland:  http://www.swisspharmtox.ch/


•	Turkey:  http://www.tfd.org.tr/


•	United Kingdom:  https://web.archive.org/web/20130410071823/http://www.bps.ac.uk/view/index.html


The  International Cannabinoid Research Society  ( ICRS ) is a  professional society  for scientific research in all fields of the  cannabinoids , based in  North Carolina , US. ICRS is one of the very few global non-profit medical societies or associations [ a ]  related to  cannabis  and  cannabinoids .


The ICRS was formally incorporated as a scientific research society in 1992. [ 1 ]  Prior to that, early ICRS Symposia were organized by various researchers in the field since 1970. Membership in the Society has risen from 50 original members in its first year to 650+ members from all over the world.


The International Cannabinoid Research Society is a:


The mission of the ICRS is to:


Since 2019, [ 3 ]  the ICRS has partnered with  Mary Ann Liebert, Inc. Publishers  to produce the  academic journal   Cannabis and Cannabinoid Research .


ICRS awards the " Raphael Mechoulam  Award in Cannabinoid Research" annually.


The Society holds an annual meeting, not available to the media, [ 4 ]  which generally alternates between North America and Europe.


The  International Union of Basic and Clinical Pharmacology  ( IUPHAR ) is a voluntary, non-profit association representing the interests of scientists in  pharmacology -related fields to facilitate  Better  Medicines  through Global Education and Research  around the world.


Established in 1959 as a section of the International Union of Physiological Sciences, IUPHAR became an independent organization in 1966 [ 1 ]  and is a member of the  International Council for Science  (ICSU). [ 2 ]   The first World Congress of Pharmacology was held in  Stockholm ,  Sweden  in 1961 and subsequently held every three years.  After 1990 the World Congresses were moved to a four-year interval. [ 3 ]   These meetings present the latest pharmacological research, technology, and methodology, and provide a forum for international collaboration and exchange of ideas.  A General Assembly, consisting of delegates from all the member societies, is convened during the congresses so member societies have an opportunity to elect the Executive Committee and vote on matters concerning the governance and activities of the union.


IUPHAR members are regional, national and special-interest societies  around the world. [ 4 ]  The various sections and committees are composed of individuals from  academia ,  pharmaceutical companies , and government organizations. IUPHAR resources are available to all members of the pharmacology-related societies that adhere to IUPHAR.


IUPHAR is divided in sectional topics. The Division of Clinical Pharmacology, including 3 subcommittees of  Developing Countries , [ 5 ]   Geriatrics , [ 6 ]  and Pharmacoepidemiology and Pharmacovigilance, focuses on the needs and research tools for clinicians.  The Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) provides a uniform guideline for naming and classifying results from the  Human Genome Project , naming proteins derived from new sequences as functional receptors and ion channels. Sections specializing in various areas of pharmacology have been established, including  Drug Metabolism and Drug Transport , [ 7 ]   Education , [ 8 ]   Gastrointestinal Pharmacology , [ 9 ]   Immunopharmacology , [ 10 ]  Pharmacology of  Natural products , [ 11 ]   Neuropsychopharmacology , [ 12 ]   Pediatrics  Clinical Pharmacology [ 13 ]  and  Pharmacogenetics  and  Pharmacogenomics . [ 14 ]   Volunteers participate in the various sections and division according to their interests and training.


A primary purpose of IUPHAR is providing global free access to a major, on-line repository of characterization data for  receptors , ion channels, enzyme target classes and  drugs  through the Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), established in 1987. The  Guide to Pharmacology  established in 2012 superseded the earlier IUPHAR-DB. This is a joint endeavor with the  British Pharmacological Society , and has been supported by the  Wellcome Trust . It includes all the  G protein -coupled receptors,  voltage-gated ion channels , 7TM receptors,  nuclear receptors ,  ligand-gated ion channels  and  Kinases  which are known to be in the  human genome . Where relevant, data on the rat and mouse  homologues  are presented to assist researchers and clinicians in developing and/or enhancing therapeutics for eventual medication in humans.


NC-IUPHAR also promulgates standards of name  nomenclature  for research in pharmacology and the related disciplines.


In general, IUPHAR offers individual pharmacologists free curriculum expertise, career development and job listings (the non-profit PharmacoCareers.org [ 15 ] ), research resources, and collaboration opportunities.  IUPHAR offers its member societies venues for participating in worldwide initiatives, publicizing member meetings and activities, nominating individuals for Young Investigator awards, and naming delegates to the quadrennial General Assemblies.  A biannual newsletter entitled  Pharmacology International  is published. [ 16 ]


As a  non-government organization  in official relations with the  World Health Organization  (WHO), IUPHAR representatives help shape international policy on  essential medicines , appropriate dose therapeutics for children, and  clinical pharmacology  core competencies among its many WHO-related activities.


The Division of Clinical Pharmacology compiled and released the Research in Humans Compendium, [ 17 ]  a free resource to provide the scientific community interested in human research with information on the design of research  protocols  to assess the effectiveness of a drug in a series of pathological conditions.


IUPHAR is involved in the development of pharmacology in  developing countries .  In conjunction with ICSU the Pharmacology for  Africa  (Phar f A) initiative was undertaken in 2006 to promote and organize pharmacology on the African continent.  The South African Society of Basic and Clinical Pharmacology is building a database and network of institutions and pharmacologists to create an infrastructure for training and funding pharmacologists.  The long-term goal is for the African continent to attain the necessary pharmacological knowledge and resources to address disease-related issues affecting the population.  As part of this mission, with the support of ICSU and the  American Society for Pharmacology and Experimental Therapeutics , the IUPHAR Education Section organized a series of workshops, mostly in Africa, to train young investigators on ethical laboratory practices, including the  three Rs of ethical use of animals .


IUPHAR Pharmacology Education Project [ 18 ]  is a website developed by IUPHAR, with support from the American Society for Pharmacology and Experimental Therapeutics (ASPET), as a learning resource to support education and training in the pharmacological sciences. The materials are intended for use by students of pharmacology, clinical pharmacologists, and others interested in the pharmacological sciences. The stated aim is to produce a simple, attractive, easily searchable resource that will support students and teachers of the biomedical sciences, medicine, nursing and pharmacy. It is also intended as an introduction to some of the new data in the IUPHAR/BPS Guide to PHARMACOLOGY, particularly for those less familiar with such material.


The early years of the 21st century will be focused on integrating basic and clinical research to implement  translational medicine  techniques more quickly.  The 9th World Conference on Clinical Pharmacology and Therapeutics in  Québec City , Canada was the last IUPHAR meeting to present clinical pharmacology separately.  The World Congress of Basic and Clinical Pharmacology in  Copenhagen , Denmark on July 17–23, 2010 [ 19 ]  was the first integrated meeting.  The merging of these different approaches to the same discipline is to accelerate the introduction of improved therapeutics for humans.


Educational components will be emphasized for both existing pharmacology programs as well as increasing and enhancing pharmacology training in developing countries.  This topic was a central theme of the 17th World Congress of Basic and Clinical Pharmacology (WCP2014) held July 13–18, 2014 in  Cape Town , South Africa. [ 20 ]   The 18th World Congress of Basic and Clinical Pharmacology (WCP2018) being held in Kyoto, Japan on July 1–6, 2018 will focus on drug development and therapeutics using new methodologies such as genome sequencing, stem cell biology, nanotechnology and systems biology. [ 21 ]


The  Safety Pharmacology Society  ( SPS ) is an organization that focuses on  safety pharmacology . [ 1 ]


The Safety Pharmacology Society was incorporated in 2000, [ 2 ]  at the time when the  International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use  was issuing ICH S7A, a regulatory guidance covering safety pharmacology, and drafting ICH S7B, which is more specific to potential effects of new drugs on  cardiac repolarization . [ 3 ]


The Safety Pharmacology Society organizes an annual meeting in the fall, comprising invited speakers and posters. [ 4 ]  This meeting has alternated between North America and Europe.


The  Society for Research on Nicotine and Tobacco  ( SRNT ) is an international  nonprofit organization  and  professional association  that studies and shares research on  nicotine  and  tobacco  use from a  public health  and scientific perspective. It is the largest organization focused on nicotine and tobacco, with members in 40 countries.


The SRNT was founded in 1994. [ 1 ]  Work from SRNT members was noted in public discussion leading up to the  Family Smoking Prevention and Tobacco Control Act  in the United States [ 2 ]  and SRNT is cited as an expert source in the Act. [ 3 ]


The SRNT has its own official scientific journal,  Nicotine & Tobacco Research , founded in 1999 and published by  Oxford University Press .


The SRNT also hosts SRNT University, a "collection of organized, curated training, scientific articles, and tools and resources for people working in Nicotine & Tobacco Research and related professions."


The SRNT does not accept funding from the  tobacco industry . The organization does accept funding from  pharmaceutical companies  that make medications to help people quit smoking. [ citation needed ]


The SRNT’s work has been used by the  World Health Organization  and governments in setting policies on topics such as  tobacco advertising ,  taxation ,  smoke-free laws , and  smoking cessation . The SRNT has been particularly active in work on the  Tobacco Master Settlement Agreement  (adopted in 1998) in the United States and on the  WHO Framework Convention on Tobacco Control  (adopted on 2003).


The society and its members have also been involved in the current debate on  tobacco harm reduction , [ 4 ]  the safety and prevalence of  e-cigarettes , [ 5 ]  and other  public health  issues.


In 2016, the Society began an annual Fellowship programme, designed to be "prestigious but not elitist". The first fellows were elected in 2017. Notable fellows include: [ 6 ]


Uppsala Monitoring Centre  ( UMC ), located in  Uppsala ,  Sweden , is the field name for the  World Health Organization   Collaborating Centre  for International Drug Monitoring. UMC works by collecting, assessing and communicating information from member countries' national  pharmacovigilance  centres in regard to the benefits, harm, effectiveness and risks of drugs. [ 1 ]


Since 1978, responsibility for managing the WHO Programme for International Drug Monitoring has been carried by UMC. [ 2 ]  In the early years the staff consisted of just three pharmacists, Sten Olsson, Cecilia Biriell and Marie Lindquist, based at the Swedish  Medical Products Agency  (Läkemedelsverket); [ 3 ]  Currently over 150 staff work in central Uppsala. The founding chairman and acting Director was Professor Åke Liljestrand. From 1990 to 2009 the Director was Professor Ralph Edwards. [ 4 ]  In 2009, Dr. Marie Lindquist became the Director until her retirement in 2020. Hervé Le Louët served from 2021 to 2022 and was succeeded by Peter Hjelmström. The Head of Research is Dr. Niklas Norén.


The work of the UMC is:


The main focus and source of data in  pharmacovigilance  are reports of ICSRs (individual case safety reports) from healthcare providers and patients in member countries of the WHO Programme. A WHO global individual case safety report database ( VigiBase ) is maintained and developed on behalf of the WHO by UMC. [ 5 ]  UMC develops and provides several tools and classifications for use by organisations involved in drug safety, including the  WHO Drug Dictionary  – with a bridge to the  MedDRA  terminology and WHO ICD –  tools for searching in the database, and a program for case report management, VigiFlow. [ 6 ]


UMC's research covers mainly three areas: data-driven discovery (especially statistical techniques), dis-proportionality analyses, interaction detection, patterns and duplicate case detection, safety surveillance and signaling (among which drug dependence and pediatric use) and benefit—risk analysis. As of 2023 over 200 scientific articles in peer-reviewed journals were linked on the centre's website. [ 7 ]


UMC has been active in initiatives to improve communication in areas related to medicines safety since 1996. [ 8 ]  The centre has been active in presenting research in the medical literature which has included some seminal works in the field. [ 7 ]  The Uppsala centre has also published books in the field of drugs safety including a regular newsletter. [ 6 ]  In 2010 the 2nd edition of a crisis management guide was published, entitled 'Expecting the Worst', also translated into other languages. [ 9 ]


UMC's role in drug safety has not been without controversy for both medicines agencies and pharmaceutical companies, despite an open approach willing to engage with many parties in the pharmaceutical world. They are closely involved in outreach to developing countries and other areas where pharmacovigilance is not yet handled. [ 7 ]


An  anaesthetic machine  ( British English ) or  anesthesia machine  ( American English ) is a  medical device  used to generate and mix a fresh gas flow of medical gases and  inhalational anaesthetic  agents for the purpose of inducing and maintaining  anaesthesia . [ 1 ]


The machine is commonly used together with a  mechanical ventilator ,  breathing system ,  suction equipment , and  patient monitoring  devices; strictly speaking, the term "anaesthetic machine" refers only to the component which generates the gas flow, but modern machines usually integrate all these devices into one combined freestanding unit, which is colloquially referred to as the "anaesthetic machine" for the sake of simplicity. In the developed world, the most frequent type in use is the  continuous-flow anaesthetic machine  or " Boyle's machine ", which is designed to provide an accurate supply of medical gases mixed with an accurate concentration of anaesthetic vapour, and to deliver this continuously to the patient at a safe  pressure  and flow. This is distinct from  intermittent-flow anaesthetic machines , which provide gas flow only on demand when triggered by the patient's own inspiration.


Simpler anaesthetic apparatus may be used in special circumstances, such as the  triservice anaesthetic apparatus , a simplified anaesthesia delivery system invented for the British  Defence Medical Services , which is light and portable and may be used for ventilation even when no medical gases are available. This device has unidirectional valves which suck in ambient air, which can be enriched with oxygen from a cylinder, with the help of a set of bellows.


The original concept of continuous-flow machines was popularised by Boyle's anaesthetic machine, invented by the British anaesthetist  Henry Boyle  at  St Bartholomew's Hospital  in  London ,  United Kingdom , in 1917, although similar machines had been in use in France and the United States. [ 2 ]  Prior to this time, anaesthesiologists often carried all their equipment with them, but the development of heavy, bulky cylinder storage and increasingly elaborate airway equipment meant that this was no longer practical for most circumstances. Contemporary anaesthetic machines are sometimes still referred to  metonymously  as "Boyle's machine", and are usually mounted on anti-static wheels for convenient transportation.


Many of the early innovations in anaesthetic equipment in the United States, including the closed circuit carbon-dioxide absorber (a.k.a. the Guedel-Foregger Midget) and diffusion of such equipment to anaesthesiologists within the United States can be attributed to  Richard von Foregger  and  The Foregger Company .


In anaesthesia, fresh gas flow is the mixture of medical gases and  volatile anaesthetic  agents which is produced by an anaesthetic machine and has not been recirculated. The flow rate and composition of the fresh gas flow is determined by the  anaesthetist . Typically the fresh gas flow emerges from the common gas outlet, a specific outlet on the anaesthetic machine to which the breathing attachment is connected. [ 3 ]


Open circuit forms of equipment, such as the Magill attachment, require high fresh gas flows (e.g. 7 litres/min) to prevent the patient from  rebreathing  their own expired carbon dioxide. Recirculating (rebreather) systems, use  soda lime  to absorb  carbon dioxide , in the scrubber, so that expired gas becomes suitable to re-use. With a very efficient recirculation system, the fresh gas flow may be reduced to the patient's minimum  oxygen  requirements (e.g. 250ml/min), plus a little volatile as needed to maintain the concentration of anaesthetic agent.


Increasing fresh gas flow to a recirculating breathing system can reduce carbon dioxide absorbent consumption. There is a cost/benefit trade-off between gas flow and use of adsorbent material when no inhalational anaesthetic agent is used which may have economic and environmental consequences. [ 3 ]


An  anesthetic vaporizer  ( American English ) or  anaesthetic vapouriser  ( British English ) is a device generally attached to an anesthetic machine which delivers a given concentration of a  volatile anesthetic  agent. It works by controlling the vaporization of anesthetic agents from liquid, and then accurately controlling the concentration in which these are added to the fresh gas flow. The design of these devices takes account of varying: ambient temperature, fresh gas flow, and agent  vapor pressure . There are generally two types of vaporizers: plenum and drawover. Both have distinct advantages and disadvantages. [ 5 ]  The  dual-circuit gas-vapor blender  is a third type of vaporizer used exclusively for the agent  desflurane .


The plenum vaporizer is driven by  positive pressure  from the  anesthetic machine , and is usually mounted on the machine. The performance of the vaporizer does not change regardless of whether the patient is breathing spontaneously or is mechanically ventilated. The internal resistance of the vaporizer is usually high, but because the supply pressure is constant the vaporizer can be accurately  calibrated  to deliver a precise concentration of  volatile anesthetic  vapor over a wide range of fresh gas flows. [ 5 ]  The plenum vaporizer is an elegant device which works reliably, without external power, for many hundreds of hours of continuous use, and requires very little maintenance.


The plenum vaporizer works by accurately splitting the incoming gas into two streams. One of these streams passes straight through the vaporizer in the bypass channel. The other is diverted into the vaporizing chamber. Gas in the vaporizing chamber becomes fully  saturated  with volatile anesthetic vapor. This gas is then mixed with the gas in the bypass channel before leaving the vaporizer.