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5-Chloro-αMT

Clinical data
ATC code	None
Legal status
Legal status	UK: Under Psychoactive Substances Act Illegal in Singapore
Identifiers
IUPAC name 1-(5-Chloro-1H-indol-3-yl)propan-2-amine
CAS Number	712-07-2
PubChem CID	12833
ChemSpider	12303
UNII	UZN5KF293Y
ChEMBL	ChEMBL1906905
CompTox Dashboard (EPA)	DTXSID10991511
Chemical and physical data
Formula	C11H13ClN2
Molar mass	208.69 g·mol
3D model (JSmol)	Interactive image
SMILES CC(Cc1cc2c1cc(cc2)Cl)N
InChI InChI=1S/C11H13ClN2/c1-7(13)4-8-6-14-11-3-2-9(12)5-10(8)11/h2-3,5-7,14H,4,13H2,1H3 Key:QMKOQSCXSYPIPB-UHFFFAOYSA-N

5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known serotonin–dopamine releasing agents (SDRAs). It is also a potent serotonin 5-HT_2A receptor agonist and hence may be a serotonergic psychedelic. The drug has been investigated in animals as a potential treatment for cocaine dependence.

Pharmacology

Pharmacodynamics

5-Chloro-αMT is a serotonin–dopamine releasing agent (SDRA). The EC₅₀Tooltip half-maximal effective concentration values of 5-chloro-αMT in evoking the in vitro release of serotonin, dopamine, and norepinephrine in rat brain synaptosomes were reported as 16 nM, 54 nM, and 3,434 nM, respectively. It had a norepinephrine:dopamine ratio of 64:1 and a dopamine:serotonin ratio of 3.4:1, indicating that it is a highly specific and fairly well-balanced SDRA.

However, 5-chloro-αMT has also been found to act as a potent full agonist of the serotonin 5-HT_2A receptor, with an EC₅₀ value of 6.27 nM and a maximal efficacy of 105%. As a serotonin 5-HT_2A receptor agonist, 5-chloro-αMT may produce psychedelic effects. Indeed, its close analogue 5-fluoro-αMT produces a strong head-twitch response in rats, a property which is highly correlated with psychedelic effects in humans, and αMT is well-established as a psychedelic drug in humans.

5-Chloro-αMT was found to not reliably produce intracranial self-administration in rats or substitute for cocaine in rats or monkeys in drug discrimination tests. It was found through study of 5-chloro-αMT in rhesus monkeys that norepinephrine release has minimal influence on the misuse potential of monoamine releasing agents (MRAs) and that loss of norepinephrine release activity does not affect efficacy in reducing cocaine self-administration in SDRAs relative to serotonin–norepinephrine–dopamine releasing agents (SNDRAs) such as naphthylisopropylamine (PAL-287). However, SDRAs like 5-chloro-αMT would be expected to produce fewer side effects (including sympathomimetic/cardiovascular effects, insomnia, hyperthermia, and anxiety) relative to SNDRAs, and thus could be better-tolerated in the treatment of cocaine dependence and other conditions.

5-Chloro-αMT is known to be a potent monoamine oxidase inhibitor (MAOI), specifically of monoamine oxidase A (MAO-A). Its IC₅₀Tooltip half-maximal inhibitory concentration values for inhibition of MAO-A and monoamine oxidase B (MAO-B) are 250 nM and 82,000 nM, respectively. Its potency in inhibiting MAO-A is similar to that of para-methoxyamphetamine (PMA). Other related drugs, such as 5-fluoro-α-methyltryptamine (5-fluoro-αMT; PAL-544), are known to be potent MAOIs similarly to 5-chloro-αMT. Potent monoamine oxidase inhibition by MRAs has been associated with dangerous and sometimes fatal toxicity in humans.

α-Ethyltryptamine (αET), an SNDRA and close structural analogue of αMT and 5-chloro-αMT, like many other releasers of both serotonin and dopamine such as MDMA, has been found to produce long-lasting serotonergic neurotoxicity in rats.

Society and culture

Legality

5-Chloro-AMT is illegal in Singapore.

See also

• 3-Chloromethamphetamine
• 4-Methyl-αMT
• 4-Hydroxy-αMT
• 4-Methyl-αET
• 5-Chloro-DMT
• 5-Cl-bk-MPA
• 5-EtO-AMT
• 5-MeO-αMT
• 5-MeO-αET
• 6-Fluoro-αMT
• 7-Methyl-αET
• 7-Chloro-AMT
• 5-API (PAL-571)
• α,N,N-TMT
• N-t-Butyltryptamine
• ST-1936

References

1. ^ Blough BE, Landavazo A, Partilla JS, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–8. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
2. ^ Banks ML, Bauer CT, Blough BE, et al. (June 2014). "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Exp Clin Psychopharmacol. 22 (3): 274–84. doi:10.1037/a0036595. PMC 4067459. PMID 24796848.
3. ^ Yamamoto T, Ueki S (January 1981). "The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs". Pharmacol. Biochem. Behav. 14 (1): 89–95. doi:10.1016/0091-3057(81)90108-8. PMID 6258178. S2CID 45561708.
4. Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y (March 1998). "Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice". Br. J. Pharmacol. 123 (5): 855–62. doi:10.1038/sj.bjp.0701695. PMC 1565246. PMID 9535013.
5. Corne SJ, Pickering RW (1967). "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia. 11 (1): 65–78. doi:10.1007/bf00401509. PMID 5302272. S2CID 3148623.
6. Araújo AM, Carvalho F, Bastos M, Guedes de Pinho P, Carvalho M (August 2015). "The hallucinogenic world of tryptamines: an updated review". Archives of Toxicology. 89 (8): 1151–1173. Bibcode:2015ArTox..89.1151A. doi:10.1007/s00204-015-1513-x. PMID 25877327. S2CID 4825078.
7. ^ Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). . Front Pharmacol. 10: 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257. {{cite journal}}: Check |url= value (help)
8. Kinemuchi H, Arai Y (October 1986). "Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine". Res. Commun. Chem. Pathol. Pharmacol. 54 (1): 125–8. doi:10.1016/0028-3908(91)90057-i. PMID 3797802. S2CID 34761939.
9. Wagmann L, Brandt SD, Kavanagh PV, Maurer HH, Meyer MR (April 2017). "In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks" (PDF). Toxicol Lett. 272: 84–93. doi:10.1016/j.toxlet.2017.03.007. PMID 28302559.
10. Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F (August 2000). "Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat". Progress in Neuro-psychopharmacology & Biological Psychiatry. 24 (6): 955–77. doi:10.1016/S0278-5846(00)00113-5. PMID 11041537. S2CID 24347904.
11. Huang XM, Johnson MP, Nichols DE (July 1991). "Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase)". European Journal of Pharmacology. 200 (1): 187–90. doi:10.1016/0014-2999(91)90686-K. PMID 1722753.
12. "Misuse of Drugs Act - Singapore Statutes Online". sso.agc.gov.sg.

• Drugs not assigned an ATC code
• 5-HT2A agonists
• Alpha-Alkyltryptamines
• Entactogens and empathogens
• Chloroarenes
• Monoamine oxidase inhibitors
• Psychedelic tryptamines
• Serotonin-dopamine releasing agents
• Serotonin receptor agonists
• Stimulants