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The actinide () or actinoid () series encompasses at least the 14 metallic chemical elements in the 5f series, with atomic numbers from 89 to 102, actinium through nobelium. Number 103, lawrencium, is also generally included despite being part of the 6d transition series. The actinide series derives its name from the f...
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Of the actinides, primordial thorium and uranium occur naturally in substantial quantities. The radioactive decay of uranium produces transient amounts of actinium and protactinium, and atoms of neptunium and plutonium are occasionally produced from transmutation reactions in uranium ores. The other actinides are purel...
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The existence of transuranium elements was suggested in 1934 by Enrico Fermi, based on his experiments. However, even though four actinides were known by that time, it was not yet understood that they formed a family similar to lanthanides. The prevailing view that dominated early research into transuranics was that th...
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Uranium and thorium were the first actinides discovered. Uranium was identified in 1789 by the German chemist Martin Heinrich Klaproth in pitchblende ore. He named it after the planet Uranus, which had been discovered eight years earlier. Klaproth was able to precipitate a yellow compound (likely sodium diuranate) by d...
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Protactinium was possibly isolated in 1900 by William Crookes. It was first identified in 1913, when Kasimir Fajans and Oswald Helmuth Göhring encountered the short-lived isotope 234mPa (half-life 1.17 minutes) during their studies of the 238U decay chain. They named the new element brevium (from Latin brevis meaning b...
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The first isotopes of transplutonium elements, americium-241 and curium-242, were synthesized in 1944 by Glenn T. Seaborg, Ralph A. James and Albert Ghiorso. Curium-242 was obtained by bombarding plutonium-239 with 32-MeV α-particles: _{94}^{239}Pu + _2^4He -> _{96}^{242}Cm + _0^1n. The americium-241 and curium-242 i...
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Einsteinium and fermium were identified in 1952–1953 in the fallout from the "Ivy Mike" nuclear test (1 November 1952), the first successful test of a hydrogen bomb. Instantaneous exposure of uranium-238 to a large neutron flux resulting from the explosion produced heavy isotopes of uranium, which underwent a series of...
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Thirty-four isotopes of actinium and eight excited isomeric states of some of its nuclides are known, ranging in mass number from 203 to 236. Three isotopes, 225Ac, 227Ac and 228Ac, were found in nature and the others were produced in the laboratory; only the three natural isotopes are used in applications. Actinium-22...
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There are 27 known isotopes of uranium, having mass numbers 215–242 (except 220). Three of them, 234U, 235U and 238U, are present in appreciable quantities in nature. Among others, the most important is 233U, which is a final product of transformation of 232Th irradiated by slow neutrons. 233U has a much higher fission...
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Among 19 isotopes of curium, ranging in mass number from 233 to 251, the most accessible are 242Cm and 244Cm; they are α-emitters, but with much shorter lifetime than the americium isotopes. These isotopes emit almost no γ-radiation, but undergo spontaneous fission with the associated emission of neutrons. More long-li...
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The 20 isotopes of californium with mass numbers 237–256 are formed in nuclear reactors; californium-253 is a β-emitter and the rest are α-emitters. The isotopes with even mass numbers (250Cf, 252Cf and 254Cf) have a high rate of spontaneous fission, especially 254Cf of which 99.7% decays by spontaneous fission. Califo...
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Long-lived isotopes of nobelium and isotopes of lawrencium (and of heavier elements) have relatively short half-lives. For nobelium, 13 isotopes are known, with mass numbers 249–260 and 262. The chemical properties of nobelium and lawrencium were studied with 255No (t1/2 = 3 min) and 256Lr (t1/2 = 35 s). The longest-li...
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The formation of actinide nuclides is primarily characterised by: Neutron capture reactions (n,γ), which are represented in the figure by a short right arrow. The (n,2n) reactions and the less frequently occurring (γ,n) reactions are also taken into account, both of which are marked by a short left arrow. Even more ...
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Thorium and uranium are the most abundant actinides in nature with the respective mass concentrations of 16 ppm and 4 ppm. Uranium mostly occurs in the Earth's crust as a mixture of its oxides in the mineral uraninite, which is also called pitchblende because of its black color. There are several dozens of other uraniu...
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The half-life of the longest-lived isotope of neptunium, 237Np, is negligible compared to the age of the Earth. Thus neptunium is present in nature in negligible amounts produced as intermediate decay products of other isotopes. Traces of plutonium in uranium minerals were first found in 1942, and the more systematic r...
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ThO2 + 2 Ca → 2 CaO + Th Sometimes thorium is extracted by electrolysis of a fluoride in a mixture of sodium and potassium chloride at 700–800 °C in a graphite crucible. Highly pure thorium can be extracted from its iodide with the crystal bar process. Uranium is extracted from its ores in various ways. In one method...
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Another separation method uses polymeric resins as a polyelectrolyte. Ion exchange processes in the resins result in separation of uranium. Uranium from resins is washed with a solution of ammonium nitrate or nitric acid that yields uranyl nitrate, UO2(NO3)2·6H2O. When heated, it turns into UO3, which is converted to U...
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Properties Actinides have similar properties to lanthanides. Just as the 4f electron shells are filled in the lanthanides, the 5f electron shells are filled in the actinides. Because the 5f, 6d, 7s, and 7p shells are close in energy, many irregular configurations arise; thus, in gas-phase atoms, just as the first 4f e...
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Actinides are typical metals. All of them are soft and have a silvery color (but tarnish in air), relatively high density and plasticity. Some of them can be cut with a knife. Their electrical resistivity varies between 15 and 150 μΩ·cm. The hardness of thorium is similar to that of soft steel, so heated pure thorium c...
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Thorium is rather active chemically. Owing to lack of electrons on 6d and 5f orbitals, tetravalent thorium compounds are colorless. At pH < 3, solutions of thorium salts are dominated by the cations [Th(H2O)8]4+. The Th4+ ion is relatively large, and depending on the coordination number can have a radius between 0.95 a...
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Uranium has a valence from 3 to 6, the last being most stable. In the hexavalent state, uranium is very similar to the group 6 elements. Many compounds of uranium(IV) and uranium(VI) are non-stoichiometric, i.e. have variable composition. For example, the actual chemical formula of uranium dioxide is UO2+x, where x var...
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The largest chemical diversity among actinides is observed in americium, which can have valence between 2 and 6. Divalent americium is obtained only in dry compounds and non-aqueous solutions (acetonitrile). Oxidation states +3, +5 and +6 are typical for aqueous solutions, but also in the solid state. Tetravalent ameri...
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Some actinides can exist in several oxide forms such as An2O3, AnO2, An2O5 and AnO3. For all actinides, oxides AnO3 are amphoteric and An2O3, AnO2 and An2O5 are basic, they easily react with water, forming bases: An2O3 + 3 H2O → 2 An(OH)3. These bases are poorly soluble in water and by their activity are close to the...
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Decomposition of certain salts of uranium, for example UO2(NO3)·6H2O in air at 400 °C, yields orange or yellow UO3. This oxide is amphoteric and forms several hydroxides, the most stable being uranyl hydroxide UO2(OH)2. Reaction of uranium(VI) oxide with hydrogen results in uranium dioxide, which is similar in its prop...
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Actinide salts can also be obtained by dissolving the corresponding hydroxides in acids. Nitrates, chlorides, sulfates and perchlorates of actinides are water-soluble. When crystallizing from aqueous solutions, these salts form hydrates, such as Th(NO3)4·6H2O, Th(SO4)2·9H2O and Pu2(SO4)3·7H2O. Salts of high-valence act...
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Actinides with oxidation state +6, except for the AnO22+-type cations, form [AnO4]2−, [An2O7]2− and other complex anions. For example, uranium, neptunium and plutonium form salts of the Na2UO4 (uranate) and (NH4)2U2O7 (diuranate) types. In comparison with lanthanides, actinides more easily form coordination compounds, ...
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Emission of neutrons during the fission of uranium is important not only for maintaining the nuclear chain reaction, but also for the synthesis of the heavier actinides. Uranium-239 converts via β-decay into plutonium-239, which, like uranium-235, is capable of spontaneous fission. The world's first nuclear reactors we...
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Alkaloids are a broad class of naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large variety of organisms including bacteria, fungi, plants, and animals. They can be purified from crud...
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The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut. Most alkaloids are basic, although some have neutral and even weakly acidic properties. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen or sulfur. Rarer still, they may contain elements such ...
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Alkaloid-containing plants have been used by humans since ancient times for therapeutic and recreational purposes. For example, medicinal plants have been known in Mesopotamia from about 2000 BC. The Odyssey of Homer referred to a gift given to Helen by the Egyptian queen, a drug bringing oblivion. It is believed that ...
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More recent classifications are based on similarity of the carbon skeleton (e.g., indole-, isoquinoline-, and pyridine-like) or biochemical precursor (ornithine, lysine, tyrosine, tryptophan, etc.). However, they require compromises in borderline cases; for example, nicotine contains a pyridine fragment from nicotinami...
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Properties Most alkaloids contain oxygen in their molecular structure; those compounds are usually colorless crystals at ambient conditions. Oxygen-free alkaloids, such as nicotine or coniine, are typically volatile, colorless, oily liquids. Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange)...
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The alkaloids content in plants is usually within a few percent and is inhomogeneous over the plant tissues. Depending on the type of plants, the maximum concentration is observed in the leaves (for example, black henbane), fruits or seeds (Strychnine tree), root (Rauvolfia serpentina) or bark (cinchona). Furthermore, ...
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In the acidic extraction, the raw plant material is processed by a weak acidic solution (e.g., acetic acid in water, ethanol, or methanol). A base is then added to convert alkaloids to basic forms that are extracted with organic solvent (if the extraction was performed with alcohol, it is removed first, and the remaind...
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Dimer alkaloids In addition to the described above monomeric alkaloids, there are also dimeric, and even trimeric and tetrameric alkaloids formed upon condensation of two, three, and four monomeric alkaloids. Dimeric alkaloids are usually formed from monomers of the same type through the following mechanisms: Mannich ...
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Most of the known functions of alkaloids are related to protection. For example, aporphine alkaloid liriodenine produced by the tulip tree protects it from parasitic mushrooms. In addition, the presence of alkaloids in the plant prevents insects and chordate animals from eating it. However, some animals are adapted to ...
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In agriculture Prior to the development of a wide range of relatively low-toxic synthetic pesticides, some alkaloids, such as salts of nicotine and anabasine, were used as insecticides. Their use was limited by their high toxicity to humans. Use as psychoactive drugs Preparations of plants and fungi containing alkal...
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In computer science, an abstract data type (ADT) is a mathematical model for data types, defined by its behavior (semantics) from the point of view of a user of the data, specifically in terms of possible values, possible operations on data of this type, and the behavior of these operations. This mathematical model con...
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Formally, an ADT is analogous to an algebraic structure in mathematics, consisting of a domain, a collection of operations, and a set of constraints the operations must satisfy. The domain is often defined implicitly, for example the free object over the set of ADT operations. The interface of the ADT typically refers ...
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Presentations of ADTs are often limited in scope to only key operations. More thorough presentations often specify auxiliary operations on ADTs, such as: (), that yields a new instance of the ADT; (s, t), that tests whether two instances' states are equivalent in some sense; (s), that computes some standard hash fun...
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In the operational style, it is often unclear how multiple instances are handled and if modifying one instance may affect others. A common style of defining ADTs writes the operations as if only one instance exists during the execution of the algorithm, and all operations are applied to that instance. For example, a st...
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Other authors disagree, arguing that a stack ADT is the same whether it is implemented with a linked list or an array, despite the difference in operation costs, and that an ADT specification should be independent of implementation. Examples Abstract variable An abstract variable may be regarded as the simplest non-t...
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Abstract stack An abstract stack is a last-in-first-out structure, It is generally defined by three key operations: , that inserts a data item onto the stack; , that removes a data item from it; and or , that accesses a data item on top of the stack without removal. A complete abstract stack definition includes also a...
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In the operational definition of an abstract stack, (S, x) returns nothing and (S) yields the value as the result but not the new state of the stack. There is then the constraint that, for any value x and any abstract variable V, the sequence of operations { (S, x); V ← (S) } is equivalent to V ← x. Since the assignmen...
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Collection Container List String Set Multiset Map Multimap Graph Tree Stack Queue Priority queue Double-ended queue Double-ended priority queue Each of these ADTs may be defined in many ways and variants, not necessarily equivalent. For example, an abstract stack may or may not have a operation that tel...
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Usually, there are many ways to implement the same ADT, using several different concrete data structures. Thus, for example, an abstract stack can be implemented by a linked list or by an array. Different implementations of the ADT, having all the same properties and abilities, can be considered semantically equivalent...
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The specification of some programming languages is intentionally vague about the representation of certain built-in data types, defining only the operations that can be done on them. Therefore, those types can be viewed as "built-in ADTs". Examples are the arrays in many scripting languages, such as Awk, Lua, and Perl,...
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This interface can be implemented in many ways. The implementation may be arbitrarily inefficient, since the formal definition of the ADT, above, does not specify how much space the stack may use, nor how long each operation should take. It also does not specify whether the stack state s continues to exist after a call...
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An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen, able to perceive ...
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The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity, which generally describes the responses of T cells (especially cytotoxic T...
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In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells or into memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells, which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers...
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Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. herpes zoster). Durable protection from infections c...
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In an electrophoresis test of blood proteins, antibodies mostly migrate to the last, gamma globulin fraction. Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ. This variant terminology fell out of use due to the correspondence b...
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The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen. Effector cells (such as macrophages or natural killer cell...
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Secreted antibodies can occur as a single Y-shaped unit, a monomer. However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six...
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Classes Antibodies can come in different varieties known as isotypes or classes. In humans there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2. The prefix "Ig" stands for immunoglobulin, while the suffix denotes the type of heavy chain th...
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The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a "naive B lymphocyte." The naive B lymphocyte expresses...
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Antibody–antigen interactions The antibody's paratope interacts with the antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants. Antibody and antigen interact by spatial complementarity (lock and key...
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At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in the bloodstream, they are said t...
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Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose, mast cells a...
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Immunoglobulin diversity Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans ...
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Somatic recombination of immunoglobulins, also known as V(D)J recombination, involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversi...
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This serves to increase the diversity of the antibody pool and impacts the antibody's antigen-binding affinity. Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a...
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Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions, found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand is broken by the activity of a series o...
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Asymmetrical antibodies Heterodimeric antibodies, which are also asymmetrical antibodies, allow for greater flexibility and new formats for attaching a variety of drugs to the antibody arms. One of the general formats for a heterodimeric antibody is the "knobs-into-holes" format. This format is specific to the heavy ch...
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Interchromosomal DNA Transposition Antibody diversification typically occurs through somatic hypermutation, class switching, and affinity maturation targeting the BCR gene loci, but on occasion more unconventional forms of diversification have been documented. For example, in the case of malaria caused by Plasmodium f...
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The study of antibodies began in 1890 when Emil von Behring and Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins. Von Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen. His idea prompted Paul Ehrli...
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Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain, and their realization that this protein is the same as the Bence-Jones protein described i...
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Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test. The Coombs test is also used for antibody screening in bl...
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Prenatal therapy Rh factor, also known as Rh D antigen, is an antigen found on red blood cells; individuals that are Rh-positive (Rh+) have this antigen on their red blood cells and individuals that are Rh-negative (Rh–) do not. During normal childbirth, delivery trauma or complications during pregnancy, blood from a f...
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Specific antibodies are produced by injecting an antigen into a mammal, such as a mouse, rat, rabbit, goat, sheep, or horse for large quantities of antibody. Blood isolated from these animals contains polyclonal antibodies—multiple antibodies that bind to the same antigen—in the serum, which can now be called antiserum...
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Antibodies used in research are some of the most powerful, yet most problematic reagents with a tremendous number of factors that must be controlled in any experiment including cross reactivity, or the antibody recognizing multiple epitopes and affinity, which can vary widely depending on experimental conditions such a...
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Before clinical trials Product safety testing: Sterility (bacteria and fungi), in vitro and in vivo testing for adventitious viruses, murine retrovirus testing..., product safety data needed before the initiation of feasibility trials in serious or immediately life-threatening conditions, it serves to evaluate dangero...
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Structure prediction and computational antibody design The importance of antibodies in health care and the biotechnology industry demands knowledge of their structures at high resolution. This information is used for protein engineering, modifying the antigen binding affinity, and identifying an epitope, of a given ant...
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There are a variety of methods used to sequence an antibody including Edman degradation, cDNA, etc.; albeit one of the most common modern uses for peptide/protein identification is liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). High volume antibody sequencing methods require computational appro...
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Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexual dysfunction, and emotional blunting. There is an increased risk of suicidal ...
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Major depressive disorder The UK National Institute for Health and Care Excellence (NICE)'s 2022 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, "unless that is the person's preference". The guidelines recommended that antidepressant treatment be consi...
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Among the 21 most commonly prescribed antidepressants, the most effective and well-tolerated are escitalopram, paroxetine, sertraline, agomelatine, and mirtazapine. For children and adolescents with moderate to severe depressive disorder, some evidence suggests fluoxetine (either with or without cognitive behavioral th...
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Antidepressants provide a modest to moderate reduction in anxiety in GAD. The efficacy of different antidepressants is similar. Social anxiety disorder Some antidepressants are used as a treatment for social anxiety disorder, but their efficacy is not entirely convincing, as only a small proportion of antidepressants ...
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In children, SSRIs are considered as a second-line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects. Sertraline and fluoxetine are effective in treating OCD for children and adolescents. Clomipramine, a TCA drug, is considered effective and useful for OCD. Howe...
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Post–traumatic stress disorder Antidepressants are one of the treatment options for PTSD. However, their efficacy is not well established. Paroxetine and sertraline have been FDA approved for the treatment of PTSD. Paroxetine has slightly higher response and remission rates than sertraline for this condition. However,...
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Eating disorders Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa. SSRIs (fluoxetine in particular) are preferred over other antidepressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term tria...
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Neuropathic pain A 2014 meta-analysis from the Cochrane Collaboration found the antidepressant duloxetine to be effective for the treatment of pain resulting from diabetic neuropathy. The same group reviewed data for amitriptyline in the treatment of neuropathic pain and found limited useful randomized clinical trial d...
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Limitations and strategies Among individuals treated with a given antidepressant, between 30% and 50% do not show a response. Approximately one-third of people achieve a full remission, one-third experience a response, and one-third are non-responders. Partial remission is characterized by the presence of poorly define...
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There is controversy amongst researchers regarding the efficacy and risk-benefit ratio of antidepressants. Although antidepressants consistently out-perform a placebo in meta-analyses, the difference is modest and it is not clear that their statistical superiority results in clinical efficacy. The aggregate effect of a...
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Critics of antidepressants maintain that the superiority of antidepressants over placebo is the result of systemic flaws in clinical trials and the research literature. Trials conducted with industry involvement tend to produce more favorable results, and accordingly many of the trials included in meta-analyses are at ...
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The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved within the following six to eight weeks of treatment with an antidepressant, switch to an antidepressant in the same class, and then to a different class. A 2006 meta-analysis review found wide variation in the findi...
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A gradual loss of therapeutic benefit occurs in a minority of people during the course of treatment. A strategy involving the use of pharmacotherapy in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies. For patients who wish to stop their antidepress...
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Researchers have developed a tool that allows people to rate their concern about common side effects of antidepressants. The tool ranks potential treatment options in a visual display that highlights the drugs with side effects of least concern to an individual. Pregnancy SSRI use in pregnancy has been associated with...
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Moreover, SSRIs inhibit nitric oxide synthesis, which plays an important role in setting the vascular tone. Several studies have pointed to an increased risk of prematurity associated with SSRI use, and this association may be due to an increased risk of pre-eclampsia during pregnancy. Antidepressant-induced mania Ano...
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Sexual dysfunction Sexual side effects are also common with SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction. Although usually reversible, these sexual side-effects can, in rare cases, continue after the drug has been completely withdrawn. In a study of 1,022 outpatients, overall ...
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Changes in weight Changes in appetite or weight are common among antidepressants but are largely drug-dependent and related to which neurotransmitters they affect. Mirtazapine and paroxetine, for example, may be associated with weight gain and/or increased appetite, while others (such as bupropion and venlafaxine) achi...
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A discontinuation syndrome can occur after stopping any antidepressant including selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). The risk is greater among those who have taken the medication for longer and when the medication i...
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The earliest and most widely known scientific theory of antidepressant action is the monoamine hypothesis, which can be traced back to the 1950s and 1960s. This theory states that depression is due to an imbalance, most often a deficiency, of the monoamine neurotransmitters, namely serotonin, norepinephrine, and/or dop...
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In 2022, a major systematic umbrella review by Joanna Moncrieff and colleagues showed that the serotonin theory of depression was not supported by evidence from a wide variety of areas. The authors concluded that there is no association between serotonin and depression, and that there is no evidence that strongly suppo...
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An alternative theory for antidepressant action proposed by certain academics such as Irving Kirsch and Joanna Moncrieff is that they work largely or entirely via placebo mechanisms. This is supported by meta-analyses of randomized controlled trials of antidepressants for depression, which consistently show that placeb...
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The placebo response, or the improvement in scores in the placebo group in clinical trials, is not only due to the placebo effect, but is also due to other phenomena such as spontaneous remission and regression to the mean. Depression tends to have an episodic course, with people eventually recovering even with no medi...
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The human serotonin transporter (SERT) and norepinephrine transporter (NET) are membrane proteins that are responsible for the reuptake of serotonin and norepinephrine. Balanced dual inhibition of monoamine reuptake may offer advantages over other antidepressants drugs by treating a wider range of symptoms. SNRIs are ...
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Tricyclic antidepressants The majority of the tricyclic antidepressants (TCAs) act primarily as serotonin–norepinephrine reuptake inhibitors (SNRIs) by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), respectively, which results in an elevation of the synaptic concentrations of these ...
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MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOIs appear to be particularly effective in the management of bipolar d...
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