1-Methyltryptamine

vanc 6 1-Methyltryptamine.svg skin-invert-image 200px Serotonin receptor agonist; Serotonin releasing agent None 7518-21-0 7088-88-2 23492 21963 125627 3330641 1-Methyl-T; 1-MT; 1-Me-T; 1-Me-tryptamine; PAL-637; PAL637 2-(1-methylindol-3-yl)ethanamine 11 14 2 CN1C=C(C2=CC=CC=C21)CCN 1S/C11H14N2/c1-13-8-9(6-7-12)10-4-2-3-5-11(10)13/h2-5,8H,6-7,12H2,1H3 CAAGZPJPCKMFBD-UHFFFAOYSA-N 1-Methyltryptamine (1-methyl-T, 1-MT or 1-Me-T; code name PAL-637) is a serotonin receptor agonist and monoamine releasing agent of the tryptamine family. Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB Alpha-ethyltryptamines as dual dopamine-serotonin releasers Bioorganic & Medicinal Chemistry Letters 24 19 4754–4758 October 2014 25193229 4211607 10.1016/j.bmcl.2014.07.062 https://www.researchgate.net/publication/265390792 Duan W, Cao D, Wang S, Cheng J Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants Chemical Reviews 124 1 124–163 January 2024 38033123 10.1021/acs.chemrev.3c00375 In addition to natural tryptamine psychedelics, numerous synthetic analogues have been reported. Compounds in Figure 5A show that, compared to the prototype tryptamine (9, Ki = 29.7 nM at h5-HT2AR, [125I]-DOI), methylation of the indole NH group slightly increases the binding affinity (1-Metryptamine, 10, Ki = 11.7 nM).136 The introduction of a methoxy group at position 5 also enhances binding affinity (11, 5-MeO-T, Ki = 1.34 nM), but a further alkylation of the indole NH with an isopropyl group almost abolished the binding affinity (12, 1-iPr-5-MeO-T, Ki = 494 nM).136 McCorvy JD Ph.D. Purdue University Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics Purdue e-Pubs 16 January 2013 https://docs.lib.purdue.edu/dissertations/AAI3545320/ 12 March 2025 It is the 1-methyl derivative of tryptamine (T; PAL-235). The drug is known to act as a serotonin 5-HT2A receptor agonist (Ki = 473–6,590nM; EC50 half-maximal effective concentration = 209–4,560nM; Emax maximal efficacy = 55–99%), as a serotonin releasing agent (EC50 half-maximal effective concentration = 53.1nM), and to be inactive in inducing the release of norepinephrine and dopamine (EC50 half-maximal effective concentration = >10,000nM). Its activities at other serotonin receptors were not reported. However, in another study, 1-methyltryptamine showed weak affinity for several other serotonin and related receptors. Hogendorf AS, Hogendorf A, Kurczab R, Satała G, Lenda T, Walczak M, Latacz G, Handzlik J, Kieć-Kononowicz K, Wierońska JM, Woźniak M, Cieślik P, Bugno R, Staroń J, Bojarski AJ Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol Sci Rep 7 1 1444 May 2017 28473721 10.1038/s41598-017-00822-4 free 5431432 1-Methyltryptamine shows dramatically reduced affinity and activational potency as well as reduced efficacy at the serotonin 5-HT2A receptor compared to tryptamine (which showed Ki = 13.1nM; EC50 half-maximal effective concentration = 7.36–99nM; Emax maximal efficacy = 101–104%). It also shows slightly reduced potency as a serotonin releasing agent and abolished activity as a releaser of norepinephrine and dopamine relative to tryptamine (which had EC50 half-maximal effective concentration = 32.6nM, 716nM, and 164nM, respectively). Analogues of 1-methyltryptamine, like 1-methylserotonin and 1-iPr-5-MeO-T, have been studied. Braden MR, Nichols DE Assessment of the roles of serines 5.43(239) and 5.46(242) for binding and potency of agonist ligands at the human serotonin 5-HT2A receptor Molecular Pharmacology 72 5 1200–1209 November 2007 17715398 10.1124/mol.107.039255 https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=f8f6db4f799a4e416aa2cc94665b10329ac6f5a8 subscription Similarly to the case of 1-methyltryptamine contrasted with tryptamine, they show dramatically reduced affinities and activational potencies at the human serotonin 5-HT2A receptor relative to their 1-unsubstituted counterparts (serotonin and 5-methoxytryptamine, respectively). See also Substituted tryptamine 1-Methyl-DMT 1-Methylpsilocin Lespedamine (1-methoxy-DMT) 1-Propyl-5-MeO-AMT O-4310 (1-isopropyl-6-fluoropsilocin) CP-132,484 2-Methyltryptamine 5-Methyltryptamine References External links 1-Methyl-T - Isomer Design Category:5-HT2A agonists Category:1-Alkyltryptamines Category:Serotonin releasing agents