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 ident ...

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

into the neuronal synaptic cleft. 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 synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

efflux Efflux may refer to: * Efflux (microbiology), a mechanism responsible for moving compounds out of cells * e-flux, a publishing platform and archive See also * Efflux time, part of a measure of paint viscosity * Flux (biology) In general, flux ...

at other types of monoamine neurons. SSRAs have been used clinically as

appetite suppressant An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" and ...

s, and they have also been proposed as novel

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s and anxiolytics with the potential for a faster onset of action and superior efficacy relative to the selective serotonin reuptake inhibitors (SSRIs). A closely related type of drug is a serotonin reuptake inhibitor (SRI).

Examples and use of SRAs

Amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

s like

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...

, MDEA,

MDA MDA, mda, or ''variation'', may refer to: Places * Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics * Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...

, and MBDB, among other relatives (see

MDxx Substituted methylenedioxy- phenethylamines (MDxx) are a large chemical class of derivatives of the phenethylamines, which includes many psychoactive drugs that act as entactogens, psychedelics, and/or stimulants, as well as entheogens. These a ...

), are

recreational drug Recreational drug use indicates 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 by modifying the perceptions and emotions of the user. When a ...

s termed entactogens. 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 the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

s such as those in the 5-HT₂ subfamily.

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.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212102s003lb ...

, chlorphentermine, and

aminorex Aminorex (Menocil, Apiquel, aminoxaphen, aminoxafen, McN-742) is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension. In the U.S., it is an illegal Schedule I drug, meani ...

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

s but were discontinued due to concerns of

cardiac valvulopathy Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic ...

. This side effect has been attributed to their additional action of potent

agonism Agonism (from Greek ἀγών '' agon'', "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 ...

of the 5-HT_2B receptor. The designer drug

4-methylaminorex 4-Methylaminorex (4-MAR, 4-MAX) is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a s ...

, which is an SNDRA and 5-HT_2B agonist, has been reported to cause this effect as well. Many tryptamines, such as

DMT ''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a derivative and a structural analog of tryptamine. It is used as a ...

, DET, DPT,

DiPT Diisopropyltryptamine (; also known as ''N,N''-diisopropyltryptamine or DiPT) is a psychedelic hallucinogenic drug of the tryptamine family that has a unique effect. While the majority of hallucinogens affect the visual sense, DiPT is primarily ...

, psilocin, and bufotenin, are SRAs as well as non-selective serotonin receptor agonists. These drugs are serotonergic psychedelics, which is a consequence of their ability to activate the 5-HT_2A receptor. αET and αMT, also tryptamines, are SNDRAs and non-selective serotonin receptor agonists that were originally thought to be

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a 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 antidepressants, espe ...

s and were formerly used as

s. They have since been discontinued and are now encountered solely as recreational drugs.

Indeloxazine Indeloxazine (INN) (Elen, Noin) is an antidepressant and cerebral activator that was marketed in Japan and South Korea by Yamanouchi Pharmaceutical Co., Ltd for the treatment of psychiatric symptoms associated with cerebrovascular diseases, ...

is an SRA and norepinephrine reuptake inhibitor that was formerly used as an antidepressant, nootropic, and neuroprotective.

List of SSRAs

Pharmaceutical drugs

* Chlorphentermine (Apsedon, Desopimon, Lucofen) *

Cloforex Cloforex (Oberex) is an anorectic of the amphetamine class. It is a prodrug to chlorphentermine. It never became a mass produced drug in part due to the side effects found in mice. Mice who consumed 75 mg of cloforex a day experienced weight lo ...

(Oberex) (

prodrug A prodrug is a 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 used to improve how the drug ...

of chlorphentermine) *

Dexfenfluramine Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotonergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain. It is the d- enantiomer of fenfluramine an ...

(Redux) (

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

of fenfluramine) * Etolorex (

of chlorphentermine; never marketed) *

(Pondimin, Fen-Phen) *

Flucetorex Flucetorex (INN) is an amphetamine. It was investigated as an anorectic, but does not appear to have ever been marketed. It is related to fenfluramine. See also * Benfluorex * Fludorex * Tiflorex Tiflorex, formerly known as flutiorex, is a s ...

(related to chlorphentermine; never marketed) *

(Elen, Noin) (non-selective; discontinued) *

Levofenfluramine Levofenfluramine (INN), or (−)-3-trifluoromethyl-''N''-ethylamphetamine, also known as (−)-fenfluramine or (''R'')-fenfluramine, is a drug of the amphetamine family that, itself (i.e., in enantiopure form), was never marketed. It is the levo ...

(

of fenfluramine) * Carbamazepine (Equetro, Epitol, and many other variations)

Research chemicals

Amiflamine Amiflamine (FLA-336) is a reversible inhibitor of monoamine oxidase A (MAO-A), thereby being a RIMA, and, to a lesser extent, semicarbazide-sensitive amine oxidase (SSAO), as well as a serotonin releasing agent (SRA). It is a derivative of the p ...

(FLA-336) *

Viqualine Viqualine (INN) (developmental code name PK-5078) is an antidepressant and anxiolytic drug that was never marketed. It acts as a potent and selective serotonin releasing agent and serotonin reuptake inhibitor. In addition, viqualine displaces d ...

(PK-5078) *

2-Methyl-3,4-methylenedioxyamphetamine 2-Methyl-3,4-methylenedioxyamphetamine (2-methyl-MDA) is an entactogen and psychedelic drug, psychedelic drug of the substituted amphetamine, amphetamine class. It acts as a selective serotonin releasing agent (SSRA), with IC50, IC50 values of 93 ...

(2-Methyl-MDA) *

3-Methoxy-4-methylamphetamine 3-Methoxy-4-methylamphetamine (MMA) is an entactogen and psychedelic drug of the phenethylamine and amphetamine classes. It was first synthesized in 1970 and was encountered as a street drug in Italy in the same decade.de Zorzi C, Cavalli A, Un ...

(MMA) * 3-Methyl-4,5-methylenedioxyamphetamine (5-Methyl-MDA) * 3,4-Ethylenedioxy-''N''-methylamphetamine (EDMA) *

4-Methoxyamphetamine ''para''-Methoxyamphetamine (PMA), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or ent ...

(PMA) * 4-Methoxy-''N''-ethylamphetamine (PMEA) * 4-Methoxy-''N''-methylamphetamine (PMMA) *

4-Methylthioamphetamine 4-Methylthioamphetamine (4-MTA) is a designer drug of the substituted amphetamine class developed in the 1990s by a team led by David E. Nichols, an American pharmacologist and medical chemist, at Purdue University. It acts as a non-neurotoxic hi ...

(4-MTA) * 5-(2-Aminopropyl)-2,3-dihydrobenzofuran (5-APDB) * 5-Indanyl-2-aminopropane (IAP) * 5-Methoxy-6-methylaminoindane (MMAI) * 5-Trifluoromethyl-2-aminoindane (TAI) *

5,6-Methylenedioxy-2-aminoindane MDAI (5,6-methylenedioxy-2-aminoindane) is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) ''in vitro'' and produces entac ...

(MDAI) * 5,6-Methylenedioxy-''N''-methyl-2-aminoindane (MDMAI) *

6-Chloro-2-aminotetralin 6-Chloro-2-aminotetralin (6-CAT) is a drug which acts as a selective serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the releasing agent, release of serotonin into the neuronal synaptic cleft. A selecti ...

(6-CAT) * 6-Tetralinyl-2-aminopropane (TAP) * 6,7-Methylenedioxy-2-aminotetralin (MDAT) *

6,7-Methylenedioxy-N-methyl-2-aminotetralin MDMAT (6,7-methylenedioxy-''N''-methyl-2-aminotetralin) is a putative, non-neurotoxic, selective serotonin releasing agent (SSRA) and entactogen drug. It is the ''N''- methylated derivative of MDAT, similarly to the relationship of MDMA to MDA ...

(MDMAT) * ''N''-Ethyl-5-trifluoromethyl-2-aminoindane (ETAI) * 6-(2-aminopropil)benzofurans (6-APB) * 5-(2-aminopropyl)benzofuran (5-APB)

References

External links

* {{TAAR ligands TAAR1 agonists VMAT inhibitors