5-Chloro-αMT

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = 1-(5-Chloro-1H-indol-3-yl)propan-2-amine

| image = 5-Chloro-3-(2-aminopropyl)indole.svg

| image2 = 5-Chloro-AMT 3D BS.png

| CAS_number = 712-07-2

| ATC_prefix = None

| ATC_suffix =

| PubChem = 12833

| DrugBank =

| ChemSpiderID = 12303

| ChEMBL = 1906905

| UNII = UZN5KF293Y

| chemical_formula = |C=11|H=13|Cl=1|N=2

| smiles = CC(Cc1c[nH]c2c1cc(cc2)Cl)N

| StdInChI = 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

| StdInChIKey = QMKOQSCXSYPIPB-UHFFFAOYSA-N

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category=

| legal_AU =

| legal_CA =

| legal_UK = PSA

| legal_US =

| legal_status = Illegal in Singapore

| routes_of_administration =

}}

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).{{cite journal |vauthors=Blough BE, Landavazo A, Partilla JS | title = Alpha-ethyltryptamines as dual dopamine-serotonin releasers | journal = Bioorganic & Medicinal Chemistry Letters | volume = 24 | issue = 19 | pages = 4754–8 |date=October 2014 | pmid = 25193229 | doi = 10.1016/j.bmcl.2014.07.062 |display-authors=etal | pmc=4211607}}{{cite journal |vauthors=Banks ML, Bauer CT, Blough BE | title = Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys | journal = Exp Clin Psychopharmacol | volume = 22 | issue = 3 | pages = 274–84 |date=June 2014 | pmid = 24796848 | doi = 10.1037/a0036595 | url = http://content.apa.org/journals/pha/22/3/274|display-authors=etal | pmc=4067459}} It is also a potent serotonin 5-HT2A 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 {{Abbrlink|EC50|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{{nbsp}}nM, 54{{nbsp}}nM, and 3,434{{nbsp}}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-HT2A receptor, with an EC50 value of 6.27{{nbsp}}nM and a maximal efficacy of 105%. As a serotonin 5-HT2A receptor agonist, 5-chloro-αMT may produce psychedelic effects.{{cite journal |vauthors=Yamamoto T, Ueki S | title = The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs | journal = Pharmacol. Biochem. Behav. | volume = 14 | issue = 1 | pages = 89–95 |date=January 1981 | pmid = 6258178 | doi = 10.1016/0091-3057(81)90108-8| s2cid = 45561708 }} Indeed, its close analogue 5-fluoro-αMT produces a strong head-twitch response in rats,{{cite journal |vauthors=Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y | title = Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice | journal = Br. J. Pharmacol. | volume = 123 | issue = 5 | pages = 855–62 |date=March 1998 | pmid = 9535013 | pmc = 1565246 | doi = 10.1038/sj.bjp.0701695 }} a property which is highly correlated with psychedelic effects in humans,{{cite journal |vauthors=Corne SJ, Pickering RW | title = A possible correlation between drug-induced hallucinations in man and a behavioural response in mice | journal = Psychopharmacologia | volume = 11 | issue = 1 | pages = 65–78 | year = 1967 | pmid = 5302272 | doi = 10.1007/bf00401509| s2cid = 3148623 }} and αMT is well-established as a psychedelic drug in humans.{{cite journal | vauthors = Araújo AM, Carvalho F, Bastos M, Guedes de Pinho P, Carvalho M | title = The hallucinogenic world of tryptamines: an updated review | journal = Archives of Toxicology | volume = 89 | issue = 8 | pages = 1151–1173 | date = August 2015 | pmid = 25877327 | doi = 10.1007/s00204-015-1513-x | bibcode = 2015ArTox..89.1151A | s2cid = 4825078 }}

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).{{cite journal | vauthors = Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK | title = Amphetamine Derivatives as Monoamine Oxidase Inhibitors | journal = Front Pharmacol | volume = 10 | issue = | page = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free}}{{cite journal |vauthors=Kinemuchi H, Arai Y | title = Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine | journal = Res. Commun. Chem. Pathol. Pharmacol. | volume = 54 | issue = 1 | pages = 125–8 |date=October 1986 | pmid = 3797802 | doi = 10.1016/0028-3908(91)90057-i| s2cid = 34761939 }} Its {{Abbrlink|IC50|half-maximal inhibitory concentration}} values for inhibition of MAO-A and monoamine oxidase B (MAO-B) are 250{{nbsp}}nM and 82,000{{nbsp}}nM, respectively. Its potency in inhibiting MAO-A is similar to that of para-methoxyamphetamine (PMA).{{cite journal | vauthors = Wagmann L, Brandt SD, Kavanagh PV, Maurer HH, Meyer MR | title = In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks | journal = Toxicol Lett | volume = 272 | issue = | pages = 84–93 | date = April 2017 | pmid = 28302559 | doi = 10.1016/j.toxlet.2017.03.007 | url = https://researchonline.ljmu.ac.uk/id/eprint/5909/1/TOXLET-D-17-00086R1_accepted_uncorected.pdf}}{{cite journal |vauthors=Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F | title = Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat | journal = Progress in Neuro-psychopharmacology & Biological Psychiatry | volume = 24 | issue = 6 | pages = 955–77 |date=August 2000 | pmid = 11041537 | doi = 10.1016/S0278-5846(00)00113-5| s2cid = 24347904 }} 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.{{cite journal |vauthors=Huang XM, Johnson MP, Nichols DE | title = Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase) | journal = European Journal of Pharmacology | volume = 200 | issue = 1 | pages = 187–90 |date=July 1991 | pmid = 1722753 | doi = 10.1016/0014-2999(91)90686-K}}

History

5-Chloro-AMT was first described in the scientific literature by at least 1963.{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | pages = 98–144 | title = Hallucinogenic Agents | date = 1975 | publisher = Wright-Scientechnica | location = Bristol | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1 | quote = [...] 5-chloro-, but not 6-chloro-, derivatives of α-methyl- and α-ethyl-tryptamine produced behavioural changes in animals (Whittle and Young, 1963); [...]}}{{cite journal | vauthors = Whittle BA, Young EH | title = The Synthesis and Pharmacological Activity of Some Chloro-α-alkyltryptamines | journal = J Med Chem | volume = 6 | issue = | pages = 378–380 | date = July 1963 | pmid = 14184890 | doi = 10.1021/jm00340a009 | url = | quote = 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. [...]}}

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.{{cite web | title=5-Cl-AMT (5-Chloro-αMT) | website=АИПСИН | date=14 October 2020 | url=https://aipsin.com/newsubstance/539/ | language=ru | access-date=15 June 2025}}{{cite web | title=5-Cl-AMT | website=АИПСИН | date=26 May 2021 | url=https://aipsin.com/newsubstance/685/ | language=ru | access-date=15 June 2025}}

=Legal status=

5-Chloro-AMT is illegal in Singapore.{{cite web|title=Misuse of Drugs Act - Singapore Statutes Online|url=https://sso.agc.gov.sg/Act/MDA1973|website=sso.agc.gov.sg}}

See also

References

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