1-Methyltryptamine

1-Methyltryptamine
Clinical data
Other names	1-Methyl-T; 1-MT; 1-Me-T; 1-Me-tryptamine; PAL-637; PAL637
Drug class	Serotonin receptor agonist; Serotonin releasing agent
ATC code	None;
Identifiers
	IUPAC name 2-(1-methylindol-3-yl)ethanamine;
CAS Number	7518-21-0 7088-88-2;
PubChem CID	23492;
ChemSpider	21963;
ChEBI	CHEBI:125627;
ChEMBL	ChEMBL3330641;
CompTox Dashboard (EPA)	DTXSID80991164 ;
ECHA InfoCard	100.028.525
Chemical and physical data
Formula	C11H14N2
Molar mass	174.247 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1C=C(C2=CC=CC=C21)CCN;
	InChI 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.¹²³ It is the 1-methyl derivative of tryptamine (T; PAL-235).¹²³

The drug is known to act as a serotonin 5-HT_2A receptor agonist (K_i = 473–6,590 nM; EC₅₀Tooltip half-maximal effective concentration = 209–4,560 nM; E_maxTooltip 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).¹⁴ Its activities at other serotonin receptors were not reported.¹³ However, in another study, 1-methyltryptamine showed weak affinity for several other serotonin and related receptors.⁴ 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 nM; EC₅₀ = 7.36–99 nM; E_max = 101–104%).³¹⁴ 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.⁵ 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).⁵

References

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.
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. 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 (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.
Hogendorf AS, Hogendorf A, Kurczab R, Satała G, Lenda T, Walczak M, et al. (May 2017). "Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol". Sci Rep. 7 (1): 1444. doi:10.1038/s41598-017-00822-4. PMC 5431432. PMID 28473721.
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.

External links

1-Methyl-T - Isomer Design

[BloughLandavazoPartilla2014-1] 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.

[DuanCaoWang2024-2] 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. 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

[McCorvy2013-3] 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.

[HogendorfHogendorfKurczab2017-4] Hogendorf AS, Hogendorf A, Kurczab R, Satała G, Lenda T, Walczak M, et al. (May 2017). "Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol". Sci Rep. 7 (1): 1444. doi:10.1038/s41598-017-00822-4. PMC 5431432. PMID 28473721.

[BradenNichols2007-5] 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.

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External links