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Serotonin releasing agent

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Aserotonin releasing agent (SRA) is a type of drug that induces the releaseofserotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons.^[1]

SSRAs have been used clinically as appetite suppressants, and they have also been proposed as novel antidepressants and anxiolytics with the potential for a faster onset of action and superior efficacy relative to the selective serotonin reuptake inhibitors (SSRIs).^[2]

A closely related type of drug is a serotonin reuptake inhibitor (SRI).

Examples and use of SRAs

Amphetamines like MDMA, MDEA, MDA, and MBDB, 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, and aminorex, which are also amphetamines and relatives, were formerly used as appetite suppressants but were discontinued due to concerns of cardiac valvulopathy. This side effect has been attributed to their additional action of potent agonism of the 5-HT_2B receptor. The designer drug 4-methylaminorex, which is an SNDRA and 5-HT_2B agonist, has been reported to cause this effect as well.

Many tryptamines, such as DMT, DET, DPT, DiPT, psilocin, and bufotenin, are SRAs as well as non-selective serotonin receptor agonists.^[3] 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 inhibitors and were formerly used as antidepressants.^[3] 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, and neuroprotective.

List of SSRAs

Pharmaceutical drugs

Chlorphentermine (Apsedon, Desopimon, Lucofen)
Cloforex (Oberex) (prodrugofchlorphentermine)
Dexfenfluramine (Redux) (enantiomer of fenfluramine)
Etolorex (prodrugofchlorphentermine; never marketed)
Fenfluramine (Pondimin, Fen-Phen)
Flucetorex (related to chlorphentermine; never marketed)
Indeloxazine (Elen, Noin) (non-selective; discontinued)
Levofenfluramine (enantiomer of fenfluramine)
Carbamazepine (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 (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-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)

See also

Monoamine releasing agent

References

^ Marona-Lewicka D, Nichols DE (June 1994). "Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan". European Journal of Pharmacology. 258 (1–2): 1–13. CiteSeerX 10.1.1.688.1895. doi:10.1016/0014-2999(94)90051-5. PMID 7925587.

^ Scorza C, Silveira R, Nichols DE, Reyes-Parada M (July 1999). "Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action". Neuropharmacology. 38 (7): 1055–61. doi:10.1016/S0028-3908(99)00023-4. PMID 10428424. S2CID 13714807.

^ ^a ^b Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology. 231 (21): 4135–44. doi:10.1007/s00213-014-3557-7. PMC 4194234. PMID 24800892.

Further reading

Nichols DE, Marona-Lewicka D, Huang X, Johnson MP (1993). "Novel serotonergic agents". Drug Design and Discovery. 9 (3–4): 299–312. PMID 8400010.

Marona-Lewicka D, Nichols DE (December 1997). "The Effect of Selective Serotonin Releasing Agents in the Chronic Mild Stress Model of Depression in Rats". Stress. 2 (2): 91–100. doi:10.3109/10253899709014740. PMID 9787258.

Scorza C, Silveira R, Nichols DE, Reyes-Parada M (July 1999). "Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action". Neuropharmacology. 38 (7): 1055–61. doi:10.1016/S0028-3908(99)00023-4. PMID 10428424. S2CID 13714807.

Rothman RB, Baumann MH (April 2002). "Serotonin releasing agents. Neurochemical, therapeutic and adverse effects". Pharmacology Biochemistry and Behavior. 71 (4): 825–36. doi:10.1016/S0091-3057(01)00669-4. PMID 11888573. S2CID 24296122.

External links

Media related to Serotonin releasing agents at Wikimedia Commons

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