Α-Methylisotryptamine

α-Methylisotryptamine (isoAMT or α-Me-isoT) is a synthetic compound belonging to the tryptamine class, known for its psychoactive properties. As a structural analog of α-methyltryptamine (αMT), isoAMT exhibits entactogenic and psychedelic effects.

α-Methylisotryptamine

Clinical data
Other names	isoAMT; iso-αMT; α-Me-isoT; PAL-569; 1-α-Methyltryptamine; 1-API; 1-IT; α-Methyl-isotryptamine
Drug class	Serotonin–norepinephrine releasing agent; Serotonin receptor agonist
Identifiers
IUPAC name 1-indol-1-ylpropan-2-amine
CAS Number	1227465-67-9
PubChem CID	20806570
ChemSpider	19644583
Chemical and physical data
Formula	C11H14N2
Molar mass	174.247 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CN1C=CC2=CC=CC=C21)N
InChI InChI=1S/C11H14N2/c1-9(12)8-13-7-6-10-4-2-3-5-11(10)13/h2-7,9H,8,12H2,1H3 Key:OZPPCCIRSILHOZ-UHFFFAOYSA-N

Pharmacology

α-Methylisotryptamine is a monoamine releasing agent and serotonin receptor agonist of the isotryptamine group.^[1][2][3][4] It is the isotryptamine homologue of α-methyltryptamine (αMT), which is a more well-known serotonergic psychedelic, entactogen, and stimulant of the tryptamine family with similar pharmacological actions.^[4][5][6]

Like αMT, α-methylisotryptamine is a monoamine releasing agent.^[1][2] As the (–)-enantiomer, it specifically acts as a preferential serotonin and norepinephrine releasing agent (SNRA), with EC₅₀Tooltip half-maximal effective concentration values of 177 nM for serotonin release, 81 nM for norepinephrine release, and 1,062 nM for dopamine release.^[1][2] In contrast to amphetamine and similar agents acting as potent and selective dopamine and norepinephrine releasing agents, (–)-α-methylisotryptamine showed no misuse potential in animal studies, including no cocaine-like effects in drug discrimination tests and no facilitation of intracranial self-stimulation (ICSS).^[1][2] In addition to its monoamine release, α-methylisotryptamine shows affinity for serotonin 5-HT₂ receptors.^[3]

Analogs

A derivative of α-methylisotryptamine, AAZ-A-154 (DLX-001; (R)-5-MeO-N,N-dimethyl-isoAMT), is a non-hallucinogenic serotonin 5-HT_2A receptor agonist and is being developed for potential medical use in the treatment depression and other neuropsychiatric disorders.^{[7][8][9][10][11]} Other derivatives of α-methylisotryptamine have also been developed, such as the selective serotonin 5-HT_2C receptor agonists (S)-5,6-difluoro-isoAMT and Ro60-0175 ((S)-5-fluoro-6-chloro-isoAMT), among others.^{[12][13][14][15][16]}

See also

• isoDMT
• 5-MeO-isoDMT
• 6-MeO-isoDMT
• VER-3323

References

1. Bauer CT (5 July 2014). Determinants of Abuse-Related Effects of Monoamine Releasers in Rats. VCU Scholars Compass (Thesis). doi:10.25772/AN08-SZ65. Retrieved 24 November 2024.
2. Banks ML, Bauer CT, Blough BE, Rothman RB, Partilla JS, Baumann MH, et al. (June 2014). "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Experimental and Clinical Psychopharmacology. 22 (3): 274–284. doi:10.1037/a0036595. PMC 4067459. PMID 24796848.
3. Lyon RA, Titeler M, Seggel MR, Glennon RA (January 1988). "Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens". European Journal of Pharmacology. 145 (3): 291–297. doi:10.1016/0014-2999(88)90432-3. PMID 3350047.
4. "1-(1H-Indol-1-yl)propan-2-amine". PubChem. Retrieved 24 November 2024.
5. Oeri HE (May 2021). "Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy". Journal of Psychopharmacology. 35 (5): 512–536. doi:10.1177/0269881120920420. PMC 8155739. PMID 32909493.
6. Glennon RA, Dukat MG (December 2023). "α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant". ACS Pharmacology & Translational Science. 6 (12): 1780–1789. doi:10.1021/acsptsci.3c00139. PMC 10714429. PMID 38093842.
7. Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123.
8. Atiq MA, Baker MR, Voort JL, Vargas MV, Choi DS (May 2024). "Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties". Psychopharmacology. doi:10.1007/s00213-024-06599-5. PMID 38743110.
9. "DLX 1". AdisInsight. 11 December 2023. Retrieved 2 November 2024.
10. "Delving into the Latest Updates on DLX-001 with Synapse". Synapse. 1 November 2024. Retrieved 2 November 2024.
11. Rasmussen K, Engel S, Chytil M, Koenig A, Meyer R, Rus M, et al. (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 - P500: P361. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (274–275). doi:10.1038/s41386-023-01756-4. PMC 10729596. PMID 38040810.
12. Chang-Fong J, Addo J, Dukat M, Smith C, Mitchell NA, Herrick-Davis K, et al. (January 2002). "Evaluation of isotryptamine derivatives at 5-HT(2) serotonin receptors". Bioorganic & Medicinal Chemistry Letters. 12 (2): 155–158. doi:10.1016/s0960-894x(01)00713-2. PMID 11755343.
13. Nilsson BM (July 2006). "5-Hydroxytryptamine 2C (5-HT2C) receptor agonists as potential antiobesity agents". Journal of Medicinal Chemistry. 49 (14): 4023–4034. doi:10.1021/jm058240i. PMID 16821762.
14. Bishop MJ, Nilsson BM (2003). "New 5-HT2C receptor agonists". Expert Opinion on Therapeutic Patents. 13 (11): 1691–1705. doi:10.1517/13543776.13.11.1691. ISSN 1354-3776.
15. Isaac M (2005). "Serotonergic 5-HT2C receptors as a potential therapeutic target for the design antiepileptic drugs". Current Topics in Medicinal Chemistry. 5 (1): 59–67. doi:10.2174/1568026053386980. PMID 15638778.
16. Bös M, Jenck F, Martin JR, Moreau JL, Sleight AJ, Wichmann J, et al. (August 1997). "Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1-methylethylamines. Improved therapeutics for obsessive compulsive disorder". J Med Chem. 40 (17): 2762–2769. doi:10.1021/jm970030l. PMID 9276022.