1-Methyltryptamine

1-Methyltryptamine
Clinical data
Other names1-Methyl-T; 1-MT; 1-Me-T; 1-Me-tryptamine; PAL-637; PAL637
Drug classSerotonin receptor agonist; Serotonin releasing agent
Identifiers
  • 2-(1-methylindol-3-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.028.525
Chemical and physical data
FormulaC11H14N2
Molar mass174.247 g·mol−1
3D model (JSmol)
  • CN1C=C(C2=CC=CC=C21)CCN
  • InChI=1S/C11H14N2/c1-13-8-9(6-7-12)10-4-2-3-5-11(10)13/h2-5,8H,6-7,12H2,1H3
  • Key: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.[1][2][3] It is the 1-methyl derivative of tryptamine (T; PAL-235).[1][2][3]

The drug is known to act as a serotonin 5-HT2A receptor agonist (Ki = 473 nM; EC50Tooltip half-maximal effective concentration = 209–4,560 nM; EmaxTooltip maximal efficacy = 55–99%), as a serotonin releasing agent (EC50 = 53.1 nM), and to be inactive in inducing the release of norepinephrine and dopamine (EC50 = >10,000 nM).[1] Its activities at other serotonin receptors were not reported.[1][3] 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 = 13.1 nM; EC50 = 7.36–99 nM; Emax = 101–104%).[3][1] 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 = 32.6 nM, 716 nM, and 164 nM, respectively).[1]

Analogues of 1-methyltryptamine, like 1-methylserotonin and 1-iPr-5-MeO-T, have been studied.[4] 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).[4]

See also

References

  1. ^ a b c d e f Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
  2. ^ a b Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. 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
  3. ^ a b c d McCorvy JD (16 January 2013). Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics (Ph.D. thesis). Purdue University. Retrieved 12 March 2025 – via Purdue e-Pubs.
  4. ^ a b Braden MR, Nichols DE (November 2007). "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. doi:10.1124/mol.107.039255. PMID 17715398.
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.