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 Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

. 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 at other types of

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines are ...

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

anxiolytic An anxiolytic (; also antipanic or antianxiety 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 anxi ...

s with the potential for a faster onset of action and superior efficacy 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 increase the extracell ...

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 action of the serotonin transporter (SERT). This in turn leads to increase ...

(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 1,3-Benzodioxolyl-''N''-methylbutanamine (''N''-methyl-1,3-benzodioxolylbutanamine, MBDB, 3,4-methylenedioxy-''N''-methyl-α-ethylphenylethylamine) is an entactogen of the phenethylamine chemical class. It is known by the street names Eden and ...

, among other relatives (see MDxx), 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 Chlorphentermine (trade names Apsedon, Desopimon, Lucofen) is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the 4-chloro derivative of the better known appetite suppressant phentermine, which is still in ...

, 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, mea ...

, 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 of the 5-HT_2B receptor. The

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Des ...

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

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 f ...

s, such as DMT, DET,

DPT DPT may refer to: Science and medicine * Dpt (unit) (dioptre/diopter), most commonly a unit measuring refraction and power in a lens or curved mirror *Dermatopontin, a human extracellular matrix protein * Dipropyltryptamine, a psychedelic tryptami ...

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 Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, psilocine, psilocyn, or psilotsin) is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated counte ...

, and

bufotenin Bufotenin (5-HO-DMT, bufotenine) is a tryptamine derivative - more specifically, a DMT derivative - related to the neurotransmitter serotonin. It is an alkaloid found in some species of toads (especially the skin), mushrooms and plants. The na ...

, 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 the ...

s. These drugs are

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...

s, 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 Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote re ...

, and

neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...

List of SSRAs

Pharmaceutical drugs

Chlorphentermine Chlorphentermine (trade names Apsedon, Desopimon, Lucofen) is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the 4-chloro derivative of the better known appetite suppressant phentermine, which is still in ...

(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 ...

) *

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 Etolorex is an anorectic of the amphetamine class. It was never marketed. Synthesis Made by the reaction of chlorphentermine with 2-Chloroethanol. See also * 3,4-Dichloroamphetamine * Cericlamine * Chlorphentermine * Cloforex * Clortermine * Me ...

(

; never marketed) *

(Pondimin, Fen-Phen) * Flucetorex (related to

; never marketed) *

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

Levofenfluramine Levofenfluramine (International Nonproprietary Name, INN), or (−)-3-trifluoromethyl-''N''-ethylamphetamine, also known as (−)-fenfluramine or (''R'')-fenfluramine, is a drug of the substituted amphetamine, amphetamine family that, itself (i. ...

(

of fenfluramine) *

Carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

(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 (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-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-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

Examples and use of SRAs

List of SSRAs

Pharmaceutical drugs

Research chemicals

See also

References

Further reading

External links