6-Methoxytryptamine

6-Methoxytryptamine
Clinical data
Other names	6-Methoxy-T; 6-MeO-T; PAL-263; PAL263
Drug class	Monoamine releasing agent; Serotonin–norepinephrine–dopamine releasing agent; Serotonin receptor modulator
ATC code	None;
Identifiers
	IUPAC name 2-(6-methoxy-1H-indol-3-yl)ethanamine;
CAS Number	3610-36-4 ;
PubChem CID	17654;
ChemSpider	16687;
UNII	83E56U9G2L;
ChEMBL	ChEMBL337825;
CompTox Dashboard (EPA)	DTXSID80189680 ;
ECHA InfoCard	100.020.708
Chemical and physical data
Formula	C11H14N2O
Molar mass	190.246 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC1=CC2=C(C=C1)C(=CN2)CCN;
	InChI InChI=1S/C11H14N2O/c1-14-9-2-3-10-8(4-5-12)7-13-11(10)6-9/h2-3,6-7,13H,4-5,12H2,1H3; Key:VOCGEKMEZOPDFP-UHFFFAOYSA-N;

6-Methoxytryptamine (6-MeO-T; developmental code name PAL-263) is a monoamine releasing agent and serotonin receptor modulator of the tryptamine family.^[1] It is a positional isomer of 5-methoxytryptamine.^[1]

Pharmacology

6-Methoxytryptamine is a potent serotonin–norepinephrine–dopamine releasing agent (SNDRA), with EC₅₀Tooltip half-maximal effective concentration values for monoamine release induction of 53.8 nM for serotonin, 113 nM for dopamine, and 465 nM for norepinephrine in rat brain synaptosomes.^[1] It is also a full agonist of the serotonin 5-HT_2A receptor, but with very low potency; its EC₅₀ and E_maxTooltip maximal efficacy at this receptor were 2,443 nM and 111%, respectively.^[1] In a series of tryptamine derivatives, 6-methoxytryptamine was the least potent serotonin 5-HT_2A receptor agonist, while 5-methoxytryptamine was the most potent serotonin 5-HT_2A receptor agonist, with 5-methoxytryptamine showing approximately 4,857-fold higher potency in terms of serotonin 5-HT_2A receptor agonism than 6-methoxytryptamine.^[1] Conversely, whereas 6-methoxytryptamine was a potent monoamine releasing agent, 5-methoxytryptamine showed very low potency in this regard.^[1]

History

6-Methoxytryptamine was first described in the scientific literature by the 1950s.^[2]

Derivatives

Certain β-carbolines and harmala alkaloids, such as harmine, harmaline, and tetrahydroharmine, are notable in being naturally occurring cyclized tryptamine derivatives of 6-methoxytryptamine.^[3]^[4] The same is true of certain iboga alkaloids, such as tabernanthine and ibogaline.^[5]^[6]^[7]^[8] Tabernanthalog (DLX-007) is a synthetic simplified ibogalog analogue of tabernanthine that is under development for use as a potential pharmaceutical drug in the treatment of neuropsychiatric disorders.^[9]^[10]

References

1 2 3 4 5 6 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.
↑ Vane JR (March 1959). "The relative activities of some tryptamine analogues on the isolated rat stomach strip preparation". British Journal of Pharmacology and Chemotherapy. 14 (1): 87–98. doi:10.1111/j.1476-5381.1959.tb00933.x. PMC 1481817. PMID 13651584.
↑ Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252.
↑ Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, et al. (April 1998). "Investigation of hallucinogenic and related beta-carbolines". Drug and Alcohol Dependence. 50 (2): 99–107. doi:10.1016/s0376-8716(97)00163-4. PMID 9649961.
↑ Skolnick P, Popik P (1999). "Pharmacology of Ibogaine and Ibogaine-Related Alkaloids". The Alkaloids: Chemistry and Biology. Vol. 52. Elsevier. pp. 197–231. doi:10.1016/s0099-9598(08)60027-9. ISBN 978-0-12-469552-8. Retrieved 17 June 2025.
↑ Lavaud C, Massiot G (2017). "The Iboga Alkaloids" (PDF). Progress in the Chemistry of Organic Natural Products. Vol. 105. pp. 89–136. doi:10.1007/978-3-319-49712-9_2. ISBN 978-3-319-49711-2. PMID 28194562.
↑ Iyer RN, Favela D, Zhang G, Olson DE (March 2021). "The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs". Natural Product Reports. 38 (2): 307–329. doi:10.1039/d0np00033g. PMC 7882011. PMID 32794540.
↑ Hamelink CR, Townsend SD, Hughes AJ (5 September 2024). "Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids". European Journal of Organic Chemistry. 27 (36) e202400432. doi:10.1002/ejoc.202400432. ISSN 1434-193X. PMC 12393092. PMID 40895173.
↑ Chen MJ, Chen-Li D, Chisamore N, Husain MI, Di Vincenzo JD, Mansur RB, et al. (July 2025). "Non-hallucinogenic psychedelics for mood and anxiety disorders: A systematic review". Psychiatry Research. 349 116532. doi:10.1016/j.psychres.2025.116532. PMID 40354769.
↑ Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, et al. (January 2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. Bibcode:2021Natur.589..474C. doi:10.1038/s41586-020-3008-z. PMC 7874389. PMID 33299186.

External links

6-MeO-T - Isomer Design

[Blough_2014-1] 1 2 3 4 5 6 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.

[Vane_1959-2] Vane JR (March 1959). "The relative activities of some tryptamine analogues on the isolated rat stomach strip preparation". British Journal of Pharmacology and Chemotherapy. 14 (1): 87–98. doi:10.1111/j.1476-5381.1959.tb00933.x. PMC 1481817. PMID 13651584.

[TiHKAL-3] Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252.

[Grella_1998-4] Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, et al. (April 1998). "Investigation of hallucinogenic and related beta-carbolines". Drug and Alcohol Dependence. 50 (2): 99–107. doi:10.1016/s0376-8716(97)00163-4. PMID 9649961.

[Skolnick_1999-5] Skolnick P, Popik P (1999). "Pharmacology of Ibogaine and Ibogaine-Related Alkaloids". The Alkaloids: Chemistry and Biology. Vol. 52. Elsevier. pp. 197–231. doi:10.1016/s0099-9598(08)60027-9. ISBN 978-0-12-469552-8. Retrieved 17 June 2025.

[Lavaud_2017-6] Lavaud C, Massiot G (2017). "The Iboga Alkaloids" (PDF). Progress in the Chemistry of Organic Natural Products. Vol. 105. pp. 89–136. doi:10.1007/978-3-319-49712-9_2. ISBN 978-3-319-49711-2. PMID 28194562.

[Iyer_2021-7] Iyer RN, Favela D, Zhang G, Olson DE (March 2021). "The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs". Natural Product Reports. 38 (2): 307–329. doi:10.1039/d0np00033g. PMC 7882011. PMID 32794540.

[Hamelink_2024-8] Hamelink CR, Townsend SD, Hughes AJ (5 September 2024). "Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids". European Journal of Organic Chemistry. 27 (36) e202400432. doi:10.1002/ejoc.202400432. ISSN 1434-193X. PMC 12393092. PMID 40895173.

[Chen_2025-9] Chen MJ, Chen-Li D, Chisamore N, Husain MI, Di Vincenzo JD, Mansur RB, et al. (July 2025). "Non-hallucinogenic psychedelics for mood and anxiety disorders: A systematic review". Psychiatry Research. 349 116532. doi:10.1016/j.psychres.2025.116532. PMID 40354769.

[Cameron_2021-10] Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, et al. (January 2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. Bibcode:2021Natur.589..474C. doi:10.1038/s41586-020-3008-z. PMC 7874389. PMID 33299186.

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