Chemistry:5-Chloro-αMT

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5-Chloro-αMT, also known as 5-chloro-α-methyltryptamine or as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known serotonin–dopamine releasing agents (SDRAs).[1][2] It is also a potent serotonin 5-HT2A receptor agonist and hence may be a serotonergic psychedelic.[1] The drug has been investigated in animals as a potential treatment for cocaine dependence.[2]

Pharmacology

Pharmacodynamics

5-Chloro-αMT is a serotonin–dopamine releasing agent (SDRA).[2] The EC50 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.[2] 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.[2]

However, 5-chloro-αMT has also been found to act as a potent full agonist of the serotonin 5-HT2A receptor, with an EC50 value of 6.27 nM and a maximal efficacy of 105%.[1] As a serotonin 5-HT2A receptor agonist, 5-chloro-αMT may produce psychedelic effects.[1][3] Indeed, its close analogue 5-fluoro-αMT produces a strong head-twitch response in rats,[4] a property which is highly correlated with psychedelic effects in humans,[3][5] and αMT is well-established as a psychedelic drug in humans.[6]

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.[2] 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).[2] 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.[2]

5-Chloro-αMT is known to be a potent monoamine oxidase inhibitor (MAOI), specifically of monoamine oxidase A (MAO-A).[7][1][2][8] Its IC50 values for inhibition of MAO-A and monoamine oxidase B (MAO-B) are 250 nM and 82,000 nM, respectively.[7] Its potency in inhibiting MAO-A is similar to that of para-methoxyamphetamine (PMA).[7][9][10] 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.[7] Potent monoamine oxidase inhibition by MRAs has been associated with dangerous and sometimes fatal toxicity in humans.[7]

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.[11]

Chemistry

Analogues

Analogues of 5-chloro-AMT include α-methyltryptamine (AMT), 5-fluoro-AMT, 5-fluoro-AET, 5-chloro-AET, 5-chloro-DMT, 5-MeO-AMT, 6-fluoro-AMT, 7-chloro-AMT, among others. It also has structural similarities to 3-chloromethamphetamine (3-CMMA) and 5-Cl-bk-MPA.

History

5-Chloro-AMT was first described in the scientific literature by at least 1963.[12][13]

Society and culture

Recreational use

5-Chloro-AMT has been encountered as a novel designer and recreational drug in Slovenia and online in the early 2020s.[14][15]

Society and culture

Canada

5-Chloro-AMT is not an explicitly nor implicitly controlled substance in Canada as of 2025.[16]

Singapore

5-Chloro-AMT is illegal in Singapore.[17]

United States

5-Chloro-AMT is not an explicitly controlled substance in the United States.[18] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

See also

  • Substituted α-alkyltryptamine

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters 24 (19): 4754–8. October 2014. doi:10.1016/j.bmcl.2014.07.062. PMID 25193229. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "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. June 2014. doi:10.1037/a0036595. PMID 24796848. PMC 4067459. http://content.apa.org/journals/pha/22/3/274. 
  3. ↑ 3.0 3.1 "The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs". Pharmacol. Biochem. Behav. 14 (1): 89–95. January 1981. doi:10.1016/0091-3057(81)90108-8. PMID 6258178. 
  4. ↑ "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. March 1998. doi:10.1038/sj.bjp.0701695. PMID 9535013. 
  5. ↑ "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia 11 (1): 65–78. 1967. doi:10.1007/bf00401509. PMID 5302272. 
  6. ↑ "The hallucinogenic world of tryptamines: an updated review". Archives of Toxicology 89 (8): 1151–1173. August 2015. doi:10.1007/s00204-015-1513-x. PMID 25877327. Bibcode: 2015ArTox..89.1151A. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol 10. 2019. doi:10.3389/fphar.2019.01590. PMID 32038257. 
  8. ↑ "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. October 1986. doi:10.1016/0028-3908(91)90057-i. PMID 3797802. 
  9. ↑ "In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks". Toxicol Lett 272: 84–93. April 2017. doi:10.1016/j.toxlet.2017.03.007. PMID 28302559. https://researchonline.ljmu.ac.uk/id/eprint/5909/1/TOXLET-D-17-00086R1_accepted_uncorected.pdf. 
  10. ↑ "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. August 2000. doi:10.1016/S0278-5846(00)00113-5. PMID 11041537. 
  11. ↑ "Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase)". European Journal of Pharmacology 200 (1): 187–90. July 1991. doi:10.1016/0014-2999(91)90686-K. PMID 1722753. 
  12. ↑ "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. "[...] 5-chloro-, but not 6-chloro-, derivatives of α-methyl- and α-ethyl-tryptamine produced behavioural changes in animals (Whittle and Young, 1963); [...]" 
  13. ↑ "The Synthesis and Pharmacological Activity of Some Chloro-α-alkyltryptamines". J Med Chem 6 (4): 378–380. July 1963. doi:10.1021/jm00340a009. PMID 14184890. "The synthesis of eight new monochloro analogs of a-methyl- and a-ethyltryptamines are described. These compounds were prepared by condensations of 4-, 5-, 6-, and 7-chloroindole-3-aldehydes with either nitroethane or nitropropane and subsequent reduction of the condensation products with lithium aluminum hydride. The tryptamines have been found to possess stimulant and anticonvulsant properties in rodents and to produce behavioral changes in cats. [...]". 
  14. ↑ "5-Cl-AMT (5-Chloro-αMT)" (in ru). 14 October 2020. https://aipsin.com/newsubstance/539/. 
  15. ↑ "5-Cl-AMT" (in ru). 26 May 2021. https://aipsin.com/newsubstance/685/. 
  16. ↑ "Controlled Drugs and Substances Act". 5 December 2025. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  17. ↑ "Misuse of Drugs Act - Singapore Statutes Online". https://sso.agc.gov.sg/Act/MDA1973. 
  18. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 



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