A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin 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, including dopamine and norepinephrine neurons.[1]
A closely related type of drug is a serotonin reuptake inhibitor (SRI), for instance fluoxetine. However, SRAs achieve much greater increases in serotonin levels than SRIs and have far more robust of subjective effects.[2][3][4][5]
SRAs, for instance fenfluramine, have been used clinically as appetite suppressants. In addition, SSRAs have been proposed as novel antidepressants and anxiolytics, with the potential for a faster onset of action and superior effectiveness relative to the selective serotonin reuptake inhibitors (SSRIs).[3][6]
Examples and use of SRAs
editFenfluramine, 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 serotonin release and/or the additional action of potent agonism of the 5-HT2B 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, and neuroprotective.
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.
Some tryptamines, such as DMT, bufotenin, and psilocin, are SRAs as well as non-selective serotonin receptor agonists.[7][8] Psilocin is a partial releaser of serotonin, with an Emax of 54%.[8][7] These drugs are serotonergic psychedelics, which is a consequence of their ability to activate the 5-HT2A receptor. Other tryptamines, including tryptamine itself, αET, and αMT, are SNDRAs and non-selective serotonin receptor agonists.[7] αET and αMT were originally thought to be monoamine oxidase inhibitors (MAOIs) and were formerly used as antidepressants, but are now encountered solely as recreational drugs. αET and αMT are described as being entactogen-like.
List of SSRAs
editPharmaceutical drugs
edit- Chlorphentermine (Apsedon, Desopimon, Lucofen)
- Cloforex (Oberex) (prodrug of chlorphentermine)
- Dexfenfluramine (Redux) (enantiomer of fenfluramine)
- Etolorex (prodrug of chlorphentermine; 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
edit- 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)
- 5-Methoxy-2-aminoindane (MEAI, 5-MeO-AI)
- 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
editReferences
edit- ^ 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.
- ^ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Curr Top Med Chem. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID 17017961.
- ^ a b 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): 1055–1061. doi:10.1016/S0028-3908(99)00023-4. PMID 10428424. S2CID 13714807.
- ^ 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.
- ^ Marona-Lewicka D, Nichols DE (July 1998). "Drug discrimination studies of the interoceptive cues produced by selective serotonin uptake inhibitors and selective serotonin releasing agents". Psychopharmacology (Berl). 138 (1): 67–75. doi:10.1007/s002130050646. PMID 9694528.
- ^ Nichols DE, Marona-Lewicka D, Huang X, Johnson MP (1993). "Novel serotonergic agents". Drug Des Discov. 9 (3–4): 299–312. PMID 8400010.
- ^ a b c 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.
- ^ a b Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE (April 2012). "Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters". The Journal of Pharmacology and Experimental Therapeutics. 341 (1): 251–262. doi:10.1124/jpet.111.188946. PMC 3364510. PMID 22271821.
Further reading
edit- 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
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