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| Other names | 6-Methyl-T; 6-MT; 6-Me-T; PAL-522; PAL522 |
| Drug class | Serotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Serotonin–dopamine releasing agent |
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| Formula | C11H14N2 |
| Molar mass | 174.247 g·mol−1 |
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6-Methyltryptamine (6-Me-T or 6-methyl-T; developmental code name PAL-522) is a serotonin receptor modulator and monoamine releasing agent of the tryptamine family.1 It is the 6-methyl derivative of tryptamine.1
The drug acts as a potent full agonist of the serotonin 5-HT2A receptor, with an EC50Tooltip half-maximal effective concentration of 75.3 nM and an EmaxTooltip maximal efficacy of 110%.1 It is about 10-fold less potent as a serotonin 5-HT2A receptor agonist than tryptamine itself.1 In addition to its serotonin 5-HT2A receptor agonism, 6-methyltryptamine is a serotonin–dopamine releasing agent (SDRA), with EC50 values for induction of monoamine release of 51.6 nM for serotonin, 353 nM for dopamine, and >10,000 nM for norepinephrine in rat brain synaptosomes.1 It shows extremely weak affinity for the dizocilpine (MK-801) site of the NMDA receptor (IC50Tooltip half-maximal inhibitory concentration = 175,000–260,000 nM).2
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.3456789 However, given intravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-lived psychoactive effects in humans.10419
The chemical synthesis of 6-methyltryptamine has been described.1
6-Methyltryptamine was first described in the scientific literature by 1965.11 Its pharmacology was subsequently assessed in greater detail in 2014.1
See also
See also
References
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.
- Berger ML (December 2000). "Tryptamine derivatives as non-competitive N-methyl-D-aspartate receptor blockers: studies using [(3)H]MK-801 binding in rat hippocampal membranes". Neuroscience Letters. 296 (1): 29–32. doi:10.1016/s0304-3940(00)01614-1. PMID 11099826.
- 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.
- 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."
- 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.
- 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.
- 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.
- 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.
- Martin WR, Sloan JW (1970). "Effects of infused tryptamine in man". Psychopharmacologia. 18 (3): 231–237. doi:10.1007/BF00412669. PMID 4922520.
- 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). [...]
- Buznikov GA, Zherebchenko PG, Chudakova IV (1965). "Effect of various indolylalkylamines on the motor cells of mollusk embryos and the blood vessels of the rabbit ear". Bulletin of Experimental Biology and Medicine. 59 (5): 527–531. doi:10.1007/BF00783076. ISSN 0007-4888.