5-Methyltryptamine

5-MeT is known to act as a potent serotonin 5-HT_2A receptor full agonist, with an {{Abbrlink|EC₅₀|half-maximal effective concentration}} of 6.00{{nbsp}}nM and an {{Abbrlink|E_max|maximal efficacy}} of 100%. In addition, it is known to be a ligand of the serotonin 5-HT_1A{{cite journal | vauthors = Soblosky JS, Dills C, DuMontier G, Jeng I | title = Evidence for 5-HT1A binding sites in chick embryo brain and discrimination by 5-methoxytryptamine | journal = Biochem Int | volume = 14 | issue = 5 | pages = 797–803 | date = May 1987 | pmid = 2970262 | doi = | url = }} and 5-HT_2B receptors{{cite journal | vauthors = Boess FG, Martin IL | title = Molecular biology of 5-HT receptors | journal = Neuropharmacology | volume = 33 | issue = 3–4 | pages = 275–317 | date = 1994 | pmid = 7984267 | doi = 10.1016/0028-3908(94)90059-0 | url = }} and an agonist of the serotonin 5-HT_1D{{cite journal | vauthors = Cushing DJ, Baez M, Kursar JD, Schenck K, Cohen ML | title = Serotonin-induced contraction in canine coronary artery and saphenous vein: role of a 5-HT1D-like receptor | journal = Life Sci | volume = 54 | issue = 22 | pages = 1671–1680 | date = 1994 | pmid = 7909909 | doi = 10.1016/0024-3205(94)00607-5 | url = }}{{cite journal | vauthors = Uchiyama-Tsuyuki Y, Saitoh M, Muramatsu M | title = Identification and characterization of the 5-HT4 receptor in the intestinal tract and striatum of the guinea pig | journal = Life Sci | volume = 59 | issue = 25–26 | pages = 2129–2137 | date = 1996 | pmid = 8950316 | doi = 10.1016/s0024-3205(96)00569-3 | url = }} and 5-HT_2C receptors.{{cite journal | vauthors = Watts SW, Cohen ML | title = Further evidence that the guinea pig tracheal contractile serotonergic receptor is a 5-hydroxytryptamine2 receptor: use of 5-methyltryptamine and dipropyl-5-carboxamidotryptamine | journal = J Pharmacol Exp Ther | volume = 264 | issue = 1 | pages = 271–275 | date = January 1993 | pmid = 8423530 | doi = 10.1016/S0022-3565(25)10263-2| url = }}{{cite journal | vauthors = Garro MA, López de Jesús M, Ruíz de Azúa I, Callado LF, Meana JJ, Sallés J | title = Regulation of phospholipase Cbeta activity by muscarinic acetylcholine and 5-HT(2) receptors in crude and synaptosomal membranes from human cerebral cortex | journal = Neuropharmacology | volume = 40 | issue = 5 | pages = 686–95 | date = April 2001 | pmid = 11311896 | doi = 10.1016/s0028-3908(00)00206-9 | url = }}{{cite book | vauthors = van Wijngaarden I, Soudijn W | title=Pharmacochemistry Library | chapter=5-HT2A, 5-HT2B and 5-HT2C receptor ligands | publisher=Elsevier | volume=27 | date=1997 | isbn=978-0-444-82041-9 | doi=10.1016/s0165-7208(97)80013-x | page=161–197}} Similarly to tryptamine and 5-MeO-T, but in contrast to serotonin, 5-MeT shows very low potency as an agonist of the serotonin 5-HT₃ receptor ({{Abbr|EC₅₀|half-maximal effective concentration}} = 60,000{{nbsp}}nM).{{cite journal | vauthors = Bower KS, Price KL, Sturdee LE, Dayrell M, Dougherty DA, Lummis SC | title = 5-Fluorotryptamine is a partial agonist at 5-HT3 receptors, and reveals that size and electronegativity at the 5 position of tryptamine are critical for efficient receptor function | journal = Eur J Pharmacol | volume = 580 | issue = 3 | pages = 291–297 | date = February 2008 | pmid = 18082160 | pmc = 2649378 | doi = 10.1016/j.ejphar.2007.11.014 | url = }}

In addition to acting as an agonist of various serotonin receptors, 5-MeT is a monoamine releasing agent (MRA), with high selectivity for induction of serotonin release over induction of dopamine and norepinephrine release ({{Abbr|EC₅₀|half-maximal effective concentration}} = 139{{nbsp}}nM, >10,000{{nbsp}}nM, and >10,000{{nbsp}}nM, respectively, in rat brain synaptosomes). However, its potency for induction of serotonin release in this system is 23-fold lower than its potency as a serotonin 5-HT_2A receptor agonist.

Tryptamines without substitutions at the amine or alpha carbon, such as tryptamine, serotonin, and 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.{{cite journal | vauthors = Jones RS | title = Tryptamine: a neuromodulator or neurotransmitter in mammalian brain? | journal = Prog Neurobiol | volume = 19 | issue = 1–2 | pages = 117–139 | date = 1982 | pmid = 6131482 | doi = 10.1016/0301-0082(82)90023-5 | url = }}{{cite book | vauthors = Shulgin A | title=Tihkal: The Continuation | publisher=Transform Press | year=1997 | isbn=978-0-9630096-9-2 | url=https://books.google.com/books?id=jl_ik66IumUC | access-date=17 August 2024 | at=[https://www.erowid.org/library/books_online/tihkal/tihkal53.shtml #53. T] | quote = (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."}}{{cite journal | vauthors = Nichols DE | title=Structure–activity relationships of serotonin 5-HT2A agonists | journal=Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | volume=1 | issue=5 | date=2012 | issn=2190-460X | doi=10.1002/wmts.42 | doi-access=free | pages=559–579}}{{cite book | vauthors = Nichols DE | title = Chemistry and Structure-Activity Relationships of Psychedelics | series = Current Topics in Behavioral Neurosciences | volume = 36 | issue = | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | url = }}{{cite journal | vauthors = Prozialeck WC, Vogel WH | title = MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats | journal = Psychopharmacology (Berl) | volume = 60 | issue = 3 | pages = 309–310 | date = February 1979 | pmid = 108709 | doi = 10.1007/BF00426673 | url = | quote = 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.}}{{cite journal | vauthors = Martin WR, Sloan JW | title = Effects of infused tryptamine in man | journal = Psychopharmacologia | volume = 18 | issue = 3 | pages = 231–237 | date = 1970 | pmid = 4922520 | doi = 10.1007/BF00412669 | url = }} However, given intravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-lived serotonergic psychedelic effects in humans.{{cite book | vauthors = Martin WR, Sloan JW | title=Drug Addiction II | chapter=Pharmacology and Classification of LSD-like Hallucinogens | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | year=1977 | isbn=978-3-642-66711-4 | doi=10.1007/978-3-642-66709-1_3 | pages=305–368 | quote=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). [...]}}

The predicted log P of 5-MeT is 1.84 to 1.9.{{cite web | title=5-Methyltryptamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/15760 | access-date=15 January 2025}}{{cite web | title=5-methyltryptamine | website=ChemSpider | date=10 June 2024 | url=https://www.chemspider.com/Chemical-Structure.14987.html | access-date=15 January 2025}}

• 1-Methyltryptamine
• 2-Methyltryptamine
• 5-Acetyltryptamine (acetryptine)
• 5-Benzyloxytryptamine
• 5-Carboxamidotryptamine
• 5-(Nonyloxy)tryptamine

{{Reflist}}

{{Serotonin receptor modulators}}

{{Monoamine releasing agents}}

{{Tryptamines}}

{{DEFAULTSORT:Methyltryptamine, 5-}}

Category:5-HT1D agonists

Category:5-HT2A agonists

Category:5-HT2C agonists

Category:Serotonin receptor agonists

Category:Serotonin releasing agents

Category:Tryptamines