A serotonin releasing agent (SRA) is a type of drug that induces the

release Release may refer to: * Art release, the public distribution of an artistic production, such as a film, album, or song * Legal release, a legal instrument * News release, a communication directed at the news media * Release (ISUP), a code to i ...

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

into the neuronal

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in neuromuscular junction, muscles or glands. Chemical synapses allow neurons to form biological neural ...

. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

efflux at other types of monoamine neurons, including

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

neurons. SRAs, for instance

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

dexfenfluramine Dexfenfluramine, formerly sold under the brand name Redux, is a Serotonin, serotonergic drug that was used as an appetite suppressant to promote weight loss. It is the d-enantiomer of fenfluramine and is structurally similar to amphetamine, but ...

, and chlorphentermine, have been used clinically as

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

s. However, these SRAs were withdrawn from the market due to

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

in the 1990s and no SRAs were available or employable for clinical study for many years. In any case, a low-dose formulation was reintroduced for treatment of

Dravet syndrome Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures o ...

in 2020 and this allowed clinical and research use of SRAs in humans once again. Aside from use as appetite suppressants, SSRAs have been proposed as novel

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

s, with the potential for a faster onset of action and superior

effectiveness Effectiveness or effectivity is the capability of producing a desired result or the ability to produce desired output. When something is deemed effective, it means it has an intended or expected outcome, or produces a deep, vivid impression. Et ...

relative to the

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (SSRIs). A closely related type of drug is a

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...

(SRI), for instance

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

Effects and comparisons

Selectivities and serotonin increases

A number of somewhat selective SRAs have been well-studied, for instance

and ''meta''-chlorophenylpiperazine (mCPP). Although fenfluramine and mCPP are efficacious SRAs, they are also highly potent

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s of

5-HT₂ receptors, including of the serotonin 5-HT_2A, 5-HT_2B, and particularly 5-HT_2C receptors. Direct activation of serotonin receptors such as the serotonin 5-HT_2C receptor with fenfluramine has been shown to be therapeutically relevant in humans, as dexfenfluramine produces

effects even when its serotonin release is blocked by concomitant treatment with the

(SSRI)

. Similarly, mCPP is an extremely potent agonist of the serotonin 5-HT_2C receptor and produces robust effects thought to be 5-HT_2C receptor-mediated in in animals and humans, such as

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

and panic. In addition to serotonin receptor agonism, fenfluramine is also a norepinephrine releasing agent with several-fold lower potency compared to serotonin release. As such, the serotonin 5-HT₂ receptor agonism and other actions of these agents may modify their effects, and a fully selective SRA could produce very different effects. More selective SRAs than agents like fenfluramine and mCPP have been developed, for instance the 2-aminoindane MMAI and certain cathinones. Chlorphentermine is also notable in being a highly selective SRA, including having negligible activity as an agonist of all three of the serotonin 5-HT₂ receptors. 4-Methylthioamphetamine (4-MTA) was originally described as a selective SRA, but was subsequently found to efficiently induce dopamine release as well, and is also known to act as a potent

monoamine oxidase A Monoamine oxidase A, also known as MAO-A, is an enzyme ( E.C. 1.4.3.4) that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative dea ...

(MAO-A)

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

MMA Mixed martial arts (MMA) is a full-contact fighting sport based on striking and grappling; incorporating techniques from various combat sports from around the world. In the early 20th century, various inter-stylistic contests took place t ...

has been found to act as a highly selective SRA, but has also been reported to produce psychedelic-like effects in both animals and humans. SRAs achieve far greater increases in serotonin levels than SRIs and have substantially more robust of effects, both in animals and in terms of subjective effects in humans. Whereas the SSRI

can increase serotonin levels in the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

in rats by up to 4-fold, the SRA

can increase serotonin levels as much as 9- to 16-fold or more. Relatedly, genetic ablation of the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

(SERT), which results in complete loss of SERT-mediated serotonin reuptake, is associated with 4- to 6-fold elevations in brain serotonin levels. SRIs produce subtle interoceptive cues that are difficult for animals to recognize in drug discrimination testing, whereas SRAs produce robust cues that are easily recognized and learned.

Stimulant-like and rewarding effects

Certain SRAs, such as fenfluramine and chlorphentermine, do not produce locomotor activation (a

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

-like effect) in animals. Moreover, fenfluramine robustly inhibits the locomotor hyperactivity and rewarding effects induced by

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

s like

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

and

phentermine Phentermine, sold under the brand name Adipex-P among others, is a medication used together with diet and exercise to treat obesity. It is available by itself or as the combination phentermine/topiramate. Phentermine is taken by mouth. Com ...

. Whereas amphetamine and phentermine produce strong locomotor stimulation in rodents, combination of fenfluramine and phentermine results in only weak locomotor activation and substantial reduction in conditioned place preference (CPP). Fenfluramine also suppresses the subjective effects and positive mood effects of amphetamine and phentermine in humans. In spite of the preceding however, it has also been reported that the SRA

weakly but dose-dependently stimulates locomotor activity in rodents. Combination of dexfenfluramine with the selective

5-HT_2C receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.SB-242084 results in dexfenfluramine dramatically and dose-dependently enhancing locomotion. However, it has also been reported that serotonin 5-HT_2B and 5-HT_2C receptor antagonism with SB-206553 does not allow fenfluramine to produce robust hyperactivity, although further addition of amphetamine does produce marked hyperlocomotion (greater than with amphetamine alone). The reasons for these conflicting findings are unclear. In any case, in other research, serotonin 5-HT_2B receptor

knockout A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, ...

or selective serotonin 5-HT_2B receptor antagonism with RS-127445 has been found to abolish MDMA-induced serotonin release and locomotor hyperactivity. As with reported findings with fenfluramine, whereas the SRA and serotonin 5-HT_2C receptor agonist mCPP decreases locomotor activity normally, it increases locomotor activity in serotonin 5-HT_2C receptor

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

or with serotonin 5-HT_2C receptor antagonism. This increased locomotor activity could be blocked by a serotonin 5-HT_1B receptor antagonist. However, other research suggests that the serotonin 5-HT_2A receptor is also involved in mCPP-induced hyperlocomotion in the context of serotonin 5-HT_2C receptor inactivation. In contrast to fenfluramine and mCPP, the SSRI fluoxetine has no impact on locomotor activity alone or in combination with SB-242084. In addition to its modulation of locomotion, the suppressive effects of fenfluramine on drug self-administration are blocked by SB-242084. Whereas certain SRAs like fenfluramine and chlorphentermine do not increase locomotor activity, other SRAs, including

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

, MDEA, MBDB, ''para''-chloroamphetamine (PCA), (''S'')-MDA, α-methyltryptamine (αMT), and α-ethyltryptamine (αET), are able to dose-dependently increase locomotor activity. Moreover, this effect appears to be serotonin-dependent, as it can be blocked by pretreatment with SSRIs like fluoxetine (which prevent the serotonin-releasing effects of SRAs). Similarly, the non-selective

serotonin receptor antagonist A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin receptor, serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A, 5-HT2A re ...

methysergide as well as the serotonin synthesis inhibitor ''para''-chlorophenylalanine (PCPA) block the hyperlocomotion of αMT. Contrasting with the preceding findings, the suppression of locomotor activity by fenfluramine and its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

dexnorfenfluramine is not blocked by fluoxetine, indicating that it is not due to induction of serotonin release. Similarly, MMAI dose-dependently suppresses locomotor activity, and this is likewise not blocked by fluoxetine nor by the non-selective serotonin receptor antagonist metitepine. However, it was, contrarily, antagonized by the serotonin synthesis inhibitor PCPA. MDAI suppresses locomotor activity initially, but there is rebound locomotor stimulation at a high dose, and this was described as similar to the profile of MDMA. The increased locomotion induced by SRAs that cause this effect appears to be critically dependent on serotonin 5-HT_1B receptor signaling. Conversely, 5-HT_2C receptor antagonists markedly enhance the hyperlocomotion of MDMA. In terms of reinforcing properties, MDMA produces dose-dependent CPP, MDAI produces CPP, MBDB produces weak CPP, fenfluramine produces conditioned place aversion (CPA), and MMAI has no effect on place conditioning at lower doses but produces CPA similarly to fenfluramine at high doses. mCPP had no effect on place conditioning, at least in one study. SSRIs have shown highly mixed effects on place conditioning, with fluoxetine producing CPP, zimelidine producing CPP or having no effect, and

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and soci ...

producing CPA. Though zimelidine was reported to produce CPP in one study, it could also block the CPP induced by amphetamine. Effects on

intracranial self-stimulation Brain stimulation reward (BSR) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by James Olds and Peter Milner. BSR can serve as a robust operant reinforcer. Targeted stimulation activ ...

(ICSS) can be used to measure the reinforcing and misuse-related effects of drugs. ICSS is enhanced by amphetamine and is reduced by the serotonin 5-HT_2C receptor agonist Ro 60-0175, by the SRA and serotonin 5-HT_2C receptor agonist fenfluramine, and by the

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP for its ligand ketazocine, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four re ...

agonist U-69,593 in rats. The serotonin–norepinephrine–dopamine releasing agents (SNDRAs) and serotonin receptor agonists (+)-MDMA and naphthylaminopropane (NAP; PAL-287) showed mixed effects on ICSS, either augmenting or suppressing ICSS depending on the ICSS frequencies. The serotonin 5-HT_2C receptor antagonist SB-242084 completely blocked the suppressive effects of Ro 60-0175 and fenfluramine on ICSS, whereas it did not influence the effects of amphetamine or U-69,593 on ICSS. SB-242084 partially reduced the ICSS suppressive effects of (+)-MDMA and NAP and augmented their facilitatory effects on ICSS. Conversely, the non-selective serotonin receptor antagonist methysergide completely blocked the ICSS depression produced by MDMA. These findings suggest that serotonin 5-HT_2C receptor activation plays a major role in the anti-reinforcing effects of SRAs, but that other serotonin receptors may also be involved.

Psychedelic-like effects

Fenfluramine dose-dependently induces the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

, a behavioral proxy of psychedelic-like effects, and this is assumed to be due to activation of serotonin 5-HT_2A receptors. Conversely, fluoxetine does not produce head twitches at any dose. In accordance with animal findings, very high doses of fenfluramine have been reported to produce

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

-like psychedelic effects in humans. The psychedelic effects of fenfluramine may be mediated by direct serotonin 5-HT_2A receptor agonism, as other SRAs like

, PCA, and chlorphentermine have been reported not to produce the head-twitch response in animals and PCA has not been reported to produce hallucinogenic effects in humans. In contrast to fenfluramine, PCA is notably not a serotonin 5-HT_2A receptor agonist or may only act as one at high doses, chlorphentermine shows very weak or negigible activity at the serotonin 5-HT₂ receptors, and MDMA is a relatively low-potency and low-

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

of the serotonin 5-HT_2A receptor. In conflict with the preceding findings however, PCA has been reported to robustly induce the head-twitch response in animals in other studies, and this appeared to be dependent on induction of serotonin release as opposed to direct serotonin 5-HT_2A receptor agonism, since it could be largely blocked by an SRI or by serotonin synthesis inhibitor. In any case, SRAs are described as not inherently hallucinogenic in humans, and hence the induction of the head-twitch response with them has been considered a false-positive for psychedelic effects.

Antidepressant-like effects

SSRIs like fluoxetine, as well as non-selective SRIs, are used and claimed to be clinically effective in the treatment of depression. SRAs produce far more robust of increases in serotonin levels than SRIs. On the basis of these findings, it has been proposed that SSRAs may be more effective antidepressants than SSRIs and may have a faster onset of action. Accordingly, SSRAs like MMAI and 4-MTA, as well as non-selective SRAs like fenfluramine, show

-like effects in animal tests, for instance in the chronic mild stress (CMS) test and the forced swim test (FST), and show greater magnitudes of effects than SSRIs ike

sertraline Sertraline, sold under the brand name Zoloft among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, generalized anxiety disorder, socia ...

. In addition to its antidepressant-like effects, MMAI has shown

-like effects in animals. Relatedly, SRAs have been suggested for potential treatment of

anxiety disorder Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...

panic disorder Panic disorder is a mental disorder, specifically an anxiety disorder, characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath ...

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...

(OCD), and other conditions as well. Although SRAs might be more effective than SRIs for uses like depression treatment, SRAs may also have greater risks than SRIs, for instance higher risk of

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

. Tachyphylaxis to their beneficial therapeutic effects might also occur. A few SRAs have in fact already been clinically studied and/or marketed as antidepressants in the past. These include αET, which was previously marketed in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

under the brand name Monase; α-methyltryptamine (αMT), which was previously marketed in the

Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...

under the brand name Indopan; fenfluramine, which has been clinically studied for depression but was never approved for this use; and PCA, which has been clinically studied for depression but was discontinued due to animal findings of serotonergic neurotoxicity.

Examples and use of SRAs

Fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

, chlorphentermine, and aminorex, which are also amphetamines and relatives, were formerly used as

s but were discontinued due to concerns of cardiac valvulopathy. This side effect has been attributed to their serotonin release and/or the additional action of potent

agonism Agonism (from Greek 'struggle') is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks to show how indivi ...

of the 5-HT_2B receptor in the case of fenfluramine. Indeloxazine is said to be an SRA and norepinephrine reuptake inhibitor (NRI) that was formerly used as an antidepressant,

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

, and neuroprotective.

Amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

s like

, MDEA, MDA, and MBDB, among other relatives (see MDxx), are

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

s termed

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

s. They act as serotonin–norepinephrine–dopamine releasing agents (SNDRAs) and also agonize

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s, such as those in the 5-HT₂ subfamily. Some

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

s, such as DMT,

bufotenin Bufotenin, also known as dimethylserotonin or as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine (DMT) and of the neurotransmi ...

, and

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

, are SRAs as well as non-selective

serotonin receptor agonist A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...

s. Psilocin is a partial releaser of serotonin, with an of 54%. These drugs are

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s, which is a consequence of their ability to activate the 5-HT_2A receptor. Other tryptamines, including

itself, αET, and αMT, are SNDRAs and non-selective serotonin receptor agonists. αET and αMT were originally thought to act as

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

s (MAOIs) and were formerly used as

s, but are now encountered solely as

s. αET and αMT are described as being entactogen-like.

Mechanism of action

List of SRAs

Pharmaceutical drugs

Amphetamines

* Amiflamine (FLA-336) (also an MAOI) * Chlorphentermine (Apsedon, Desopimon, Lucofen) * Cloforex (Oberex) (

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

of chlorphentermine) *

Dexfenfluramine Dexfenfluramine, formerly sold under the brand name Redux, is a Serotonin, serotonergic drug that was used as an appetite suppressant to promote weight loss. It is the d-enantiomer of fenfluramine and is structurally similar to amphetamine, but ...

(Redux) (

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

of fenfluramine) * Etolorex (prodrug of chlorphentermine; never marketed) *

(Pondimin, Fen-Phen) * Flucetorex (related to chlorphentermine; never marketed) * Levofenfluramine (enantiomer of fenfluramine) * Norfenfluramine (

of fenfluramine)

Tryptamines

* α-Ethyltryptamine (αET, AET; etryptamine; Monase; withdrawn) * α-Methyltryptamine (αMT, AMT; Indopan; withdrawn) * 5-Chloro-αET * 5-Chloro-αMT * 5-Fluoro-αET * 5-Fluoro-αMT * βk-NM-αMT *

Dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT) * Methylethyltryptamine (MET) *

Psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

Bufotenin Bufotenin, also known as dimethylserotonin or as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine (DMT) and of the neurotransmi ...

Tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

Others

Carbamazepine Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...

(Equetro, Epitol, and many other variations) * Indeloxazine (Elen, Noin) (non-selective; discontinued) * Viqualine (PK-5078) (also a GABA_A receptor ; never marketed)

Recreational drugs and research chemicals

Amphetamines

* 3-Methoxy-4-methylamphetamine (MMA) * 4-Methoxyamphetamine (PMA) * 4-Methoxy-''N''-ethylamphetamine (PMEA) * 4-Methoxy-''N''-methylamphetamine (PMMA) * 4-Methylthioamphetamine (4-MTA)

=Ring-extended amphetamines

= * 2-Methyl-3,4-methylenedioxyamphetamine (2-Methyl-MDA) * 3-Methyl-4,5-methylenedioxyamphetamine (5-Methyl-MDA) * 3,4-Ethylenedioxy-''N''-methylamphetamine (EDMA) * 3,4-Methylenedioxyamphetamine (MDA) * 3,4-Methylenedioxyethylamphetamine (MDEA) * 3,4-Methylenedioxymethamphetamine (MDMA) * 5-(2-Aminopropyl)benzofuran (5-APB) * 5-(2-Aminopropyl)-2,3-dihydrobenzofuran (5-APDB) * 5-Indanyl-2-aminopropane (IAP) * 5-MABB * 5-MAPB * 6-(2-Aminopropyl)benzofuran (6-APB) * 6-MABB * 6-MAPB * 6-Tetralinyl-2-aminopropane (TAP) * ''N''-Methyl-1,3-benzodioxolylbutanamine (MBDB) * Methamnetamine (MNAP; PAL-1046) * Naphthylaminopropane (NAP; PAL-287) *

ODMA The Open Document Management API is an API that simplifies the communication of desktop applications with document management systems (DMS). ODMA standardizes the access to the DMS, which makes getting to these files as easy as if the files wer ...

* SeDMA * TDMA

=Cathinones

= * Butylone (βk-MBDB) * Mephedrone (4-methylmethcathinone; 4-MMC) *

Methylone Methylone, also known as 3,4-methylenedioxy-''N''-methylcathinone (MDMC), is an entactogen and stimulant drug of the amphetamine, cathinone, and benzodioxole families related to 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"). It is th ...

(3,4-methylenedioxymethcathinone; MDMC)

Effects and comparisons

Selectivities and serotonin increases

Stimulant-like and rewarding effects

Psychedelic-like effects

Antidepressant-like effects

Examples and use of SRAs

Mechanism of action

List of SRAs

Pharmaceutical drugs

Amphetamines

Tryptamines

Others

Recreational drugs and research chemicals

Amphetamines

=Ring-extended amphetamines

=Cathinones

Phenyloxazolamines

Aminoindanes

Aminotetralins

Phenylpiperazines

Others

See also

References

External links