1-Methyltryptamine

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| image = N-methyltryptamine.svg

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| class = Serotonin receptor agonist; Serotonin releasing agent

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| CAS_number = 7518-21-0

| CAS_supplemental = 7088-88-2

| PubChem = 23492

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| DrugBank =

| ChemSpiderID = 21963

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| ChEBI = 125627

| ChEMBL = 3330641

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| synonyms = 1-Methyl-T; 1-MT; 1-Me-T; 1-Me-tryptamine; PAL-637; PAL637

| IUPAC_name = 2-(1-methylindol-3-yl)ethanamine

| C=11 | H=14 | N=2

| SMILES = CN1C=C(C2=CC=CC=C21)CCN

| StdInChI = 1S/C11H14N2/c1-13-8-9(6-7-12)10-4-2-3-5-11(10)13/h2-5,8H,6-7,12H2,1H3

| StdInChIKey = CAAGZPJPCKMFBD-UHFFFAOYSA-N

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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.{{cite journal | vauthors = Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB | title = Alpha-ethyltryptamines as dual dopamine-serotonin releasers | journal = Bioorganic & Medicinal Chemistry Letters | volume = 24 | issue = 19 | pages = 4754–4758 | date = October 2014 | pmid = 25193229 | pmc = 4211607 | doi = 10.1016/j.bmcl.2014.07.062 | url = https://www.researchgate.net/publication/265390792 }}{{cite journal | vauthors = Duan W, Cao D, Wang S, Cheng J | title = Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants | journal = Chemical Reviews | volume = 124 | issue = 1 | pages = 124–163 | date = January 2024 | pmid = 38033123 | doi = 10.1021/acs.chemrev.3c00375 | quote = 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 }}{{cite thesis | vauthors = McCorvy JD | degree = Ph.D. | publisher = Purdue University | title=Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics | via = Purdue e-Pubs | date=16 January 2013 | url=https://docs.lib.purdue.edu/dissertations/AAI3545320/ | access-date=12 March 2025}} It is the 1-methyl derivative of tryptamine (T; PAL-235).

The drug is known to act as a serotonin 5-HT_2A receptor agonist (K_i = 473{{nbsp}}nM; {{Abbrlink|EC₅₀|half-maximal effective concentration}} = 209–4,560{{nbsp}}nM; {{Abbrlink|E_max|maximal efficacy}} = 55–99%), as a serotonin releasing agent ({{Abbr|EC₅₀|half-maximal effective concentration}} = 53.1{{nbsp}}nM), and to be inactive in inducing the release of norepinephrine and dopamine ({{Abbr|EC₅₀|half-maximal effective concentration}} = >10,000{{nbsp}}nM). Its activities at other serotonin receptors were not reported. 1-Methyltryptamine shows dramatically reduced affinity and activational potency as well as reduced efficacy at the serotonin 5-HT_2A receptor compared to tryptamine (which showed K_i = 13.1{{nbsp}}nM; {{Abbr|EC₅₀|half-maximal effective concentration}} = 7.36–99{{nbsp}}nM; {{Abbr|E_max|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 {{Abbr|EC₅₀|half-maximal effective concentration}} = 32.6{{nbsp}}nM, 716{{nbsp}}nM, and 164{{nbsp}}nM, respectively).

Analogues of 1-methyltryptamine, like 1-methylserotonin and 1-iPr-5-MeO-T, have been studied.{{cite journal | vauthors = Braden MR, Nichols DE | title = 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 | journal = Molecular Pharmacology | volume = 72 | issue = 5 | pages = 1200–1209 | date = November 2007 | pmid = 17715398 | doi = 10.1124/mol.107.039255 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=f8f6db4f799a4e416aa2cc94665b10329ac6f5a8 | url-access = subscription }} Similarly to the case of 1-methyltryptamine contrasted with tryptamine, they show dramatically reduced affinities and activational potencies at the human serotonin 5-HT_2A receptor relative to their 1-unsubstituted counterparts (serotonin and 5-methoxytryptamine, respectively).