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

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" ...

s, and they have also been proposed as novel antidepressants 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 anxiet ...

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 extracellul ...

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 incre ...

(SRI).

Examples and use of SRAs

Amphetamines like

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

, MDEA, MDA, 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 drugs termed entactogens. They act as serotonin-norepinephrine-dopamine releasing agents (SNDRAs) and also agonize serotonin receptors such as those in the 5-HT₂ subfamily. Fenfluramine,

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. D ...

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 cou ...

, 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. ...

, 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 inhibitors and were formerly used as antidepressants. They have since been discontinued and are now encountered solely as recreational drugs. Indeloxazine 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 dietary supplement, supplements or drugs and other substances that are claimed to improve cognitive function ...

, 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 (Oberex) ( prodrug of

) * Dexfenfluramine (Redux) ( enantiomer 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 * ...

( prodrug of

; never marketed) * Fenfluramine (Pondimin, Fen-Phen) * Flucetorex (related to

; never marketed) * Indeloxazine (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. ...

( enantiomer 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 m ...

(Equetro, Epitol, and many other variations)

Research chemicals

* Amiflamine (FLA-336) * Viqualine (PK-5078) * 2-Methyl-3,4-methylenedioxyamphetamine (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, U ...

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

(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-''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) * ''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