7-Methoxytryptamine

Pharmaceutical compound From Wikipedia, the free encyclopedia

7-Methoxytryptamine (7-MeO-T or 7-methoxy-T; developmental code name PAL-533) is a serotonin receptor modulator and monoamine releasing agent of the tryptamine family.^[1]^[2] It is the 7-methoxy derivative of tryptamine.^[1]

Other names7-Methoxy-T; 7-MeO-T; 7-OMe-T; PAL-533; PAL533

Drug classSerotonin receptor modulator; Serotonin 5-HT_2A receptor agonist; Serotonin releasing agent

ATC code

None

CAS Number

2436-04-6

Quick facts Clinical data, Other names ...

7-Methoxytryptamine
Clinical data

Other names	7-Methoxy-T; 7-MeO-T; 7-OMe-T; PAL-533; PAL533
Drug class	Serotonin receptor modulator; Serotonin 5-HT_2A receptor agonist; Serotonin releasing agent
ATC code	None
Identifiers
IUPAC name 2-(7-methoxy-1H-indol-3-yl)ethanamine
CAS Number	2436-04-6
PubChem CID	17087
ChemSpider	16172
UNII	SZ9QG5P86E
ChEMBL	ChEMBL3330644
Chemical and physical data
Formula	C₁₁H₁₄N₂O
Molar mass	190.246 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COC1=CC=CC2=C1NC=C2CCN
InChI InChI=1S/C11H14N2O/c1-14-10-4-2-3-9-8(5-6-12)7-13-11(9)10/h2-4,7,13H,5-6,12H2,1H3 Key:ZUJIGHUQQNOCAM-UHFFFAOYSA-N

The drug acts as a full agonist of the serotonin 5-HT_2A receptor, with an EC₅₀Tooltip half-maximal effective concentration of 496 nM and an E_maxTooltip maximal efficacy of 107%.^[1] It shows 67-fold lower potency as a serotonin 5-HT_2A receptor agonist compared to tryptamine itself.^[1] In addition to its serotonin 5-HT_2A receptor agonism, 7-methoxytryptamine is a serotonin releasing agent (SRA), with EC₅₀ values for induction of monoamine release of 44.6 nM for serotonin, 2,118 nM for dopamine, and 5,600 nM for norepinephrine in rat brain synaptosomes.^[1] The effects of 7-methoxytryptamine in rodents have been described.^[3]^[4]

Tryptamines without substitutions at the amine or alpha carbon, such as tryptamine, serotonin (5-hydroxytryptamine; 5-HT), and 5-methoxytryptamine (5-MeO-T), are known to be very rapidly metabolized and thereby inactivated by monoamine oxidase A (MAO-A) in vivo and to have very short elimination half-lives.^[5]^[6]^[7]^[8]^[9]^[10]^[11] However, given intravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-lived psychoactive effects in humans.^[12]^[6]^[1]^[11]

The chemical synthesis of 7-methoxytryptamine has been described.^[1]^[13]^[14]^[3]^[15]

7-Methoxytryptamine was first described in the scientific literature by Ernst Späth and Edgar Lederer by 1931.^[15]^[16] Its pharmacology was subsequently assessed in greater detail in 2014.^[1]

References

[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.
[2]
Keup W (1970). "Structure-Activity Relationship among Hallucinogenic Agents". Origin and Mechanisms of Hallucinations. Boston, MA: Springer US. pp. 345–376. doi:10.1007/978-1-4615-8645-6_29. ISBN 978-1-4615-8647-0.
[3]
Kalir A, Balderman D, Edery H, Porath G (1967). "7‐Methoxyindole and its Derivatives". Israel Journal of Chemistry. 5 (4): 129–136. doi:10.1002/ijch.196700026. ISSN 0021-2148.
[4]
Nichols DE, Glennon RA (1984). "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". In Jacobs BL (ed.). Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237. 7-Methoxytryptamine displayed weak behavioral activity in animals (124). [...] The 6- and 7-methoxy derivatives of DMT, 71 and 72, respectively, display a low order of behavioral activity in animals (65,86,91,93,124). [...] The 6- and 7-methoxy derivatives [of DMT] are less active than either the 4- or 5-methoxy isomers.
[5]
Jones RS (1982). "Tryptamine: a neuromodulator or neurotransmitter in mammalian brain?". Progress in Neurobiology. 19 (1–2): 117–139. doi:10.1016/0301-0082(82)90023-5. PMID 6131482.
[6]
Shulgin A (1997). Tihkal: The Continuation. Transform Press. #53. T. ISBN 978-0-9630096-9-2. Retrieved 17 August 2024. (with 250 mg, intravenously) "Tryptamine was infused intravenously over a period of up to 7.5 minutes. Physical changes included an increases in blood pressure, in the amplitude of the patellar reflex, and in pupillary diameter. The subjective changes are not unlike those seen with small doses of LSD. A point-by-point comparison between the tryptamine and LSD syndromes reveals a close similarity which is consistent with the hypothesis that tryptamine and LSD have a common mode of action."
[7]
Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X.
[8]
Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524.
[9]
Prozialeck WC, Vogel WH (February 1979). "MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats". Psychopharmacology. 60 (3): 309–310. doi:10.1007/BF00426673. PMID 108709. In contrast, MAO inhibition greatly increased brain levels of 5-HT and 5-MT (Prozialeck and Vogel, 1978). For instance, clorgyline and deprenyl increased brain levels of 5-HT 8.5-fold and 4.4-fold and of 5-MT 20-fold and 5-fold, respectively.
[10]
Boess FG, Martin IL (1994). "Molecular biology of 5-HT receptors". Neuropharmacology. 33 (3–4): 275–317. doi:10.1016/0028-3908(94)90059-0. PMID 7984267.
[11]
Martin WR, Sloan JW (1970). "Effects of infused tryptamine in man". Psychopharmacologia. 18 (3): 231–237. doi:10.1007/BF00412669. PMID 4922520.
[12]
Martin WR, Sloan JW (1977). "Pharmacology and Classification of LSD-like Hallucinogens". Drug Addiction II. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 305–368. doi:10.1007/978-3-642-66709-1_3. ISBN 978-3-642-66711-4. MARTIN and SLOAN (1970) found that intravenously infused tryptamine increased blood pressure, dilated pupils, enhanced the patellar reflex, and produced perceptual distortions. [...] Tryptamine, but not DMT, increases locomotor activity in the mouse, while both antagonize reserpine depression (V ANE et al., 1961). [...] In the rat, tryptamine causes backward locomotion, Straub tail, bradypnea and dyspnea, and clonic convulsions (TEDESCHI et al., 1959). [...] Tryptamine produces a variety of changes in the cat causing signs of sympathetic activation including mydriasis, retraction of nictitating membrane, piloerection, motor signs such as extension of limbs and convulsions and affective changes such as hissing and snarling (LAIDLAW, 1912). [...]
[13]
Repke DB, Grotjahn DB, Shulgin AT (July 1985). "Psychotomimetic N-methyl-N-isopropyltryptamines. Effects of variation of aromatic oxygen substituents". Journal of Medicinal Chemistry. 28 (7): 892–896. doi:10.1021/jm00145a007. PMID 4009612.
[14]
Sóti F, Incze M, Kardos-Balogh Z, Kajtár-Peredy M, Szántay C (1993). "Synthesis of Vinca Alkaloids and Related Compounds. LXV. Preparation of 7-Methoxytryptamine". Synthetic Communications. 23 (12): 1689–1698. doi:10.1080/00397919308011267. ISSN 0039-7911.
[15]
Späth E, Lederer E (17 September 1930). "Synthesen von 4‐Carbolinen". Berichte der deutschen chemischen Gesellschaft (A and B Series). 63 (8): 2102–2111. doi:10.1002/cber.19300630839. ISSN 0365-9488.
[16]
Manske RH (1 June 1931). "The synthesis of some indol derivatives". Canadian Journal of Research. 4 (6): 591–595. doi:10.1139/cjr31-047. ISSN 1923-4287.

7-Methoxytryptamine

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