4-HO-TMT

{{Short description|Serotonergic compound}}

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| class = Serotonin receptor agonist

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| CAS_number = 262285-41-6

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| PubChem = 17868117

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| ChemSpiderID = 13318696

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| ChEBI = 193061

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| synonyms = 4-OH-TMT; 4-hydroxy-N,N,N-trimethyltryptammonium; 4-Hydroxy-N,N,N-trimethyltryptamine; 4-HO-N,N,N-TMT; Dephosphorylated aeruginascin; Dephosphorylaeruginascin

| IUPAC_name = 2-(4-hydroxy-1H-indol-3-yl)ethyl-trimethylazanium

| C=13 | H=19 | N=2 | O=1 | charge=+

| SMILES = C[N+](C)(C)CCC1=CNC2=C1C(=CC=C2)O

| StdInChI = 1S/C13H18N2O/c1-15(2,3)8-7-10-9-14-11-5-4-6-12(16)13(10)11/h4-6,9,14H,7-8H2,1-3H3/p+1

| StdInChIKey = RMPOMMZKJNCOTM-UHFFFAOYSA-O

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4-HO-TMT, or 4-OH-TMT, also known as 4-hydroxy-N,N,N-trimethyltryptammonium or as dephosphorylated aeruginascin, is a substituted tryptamine derivative and the active form of aeruginascin (4-PO-TMT), analogously to how psilocin (4-HO-DMT) is the active form of psilocybin (4-PO-DMT).{{cite journal | vauthors = Chadeayne AR, Pham DN, Reid BG, Golen JA, Manke DR | title = Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity | journal = ACS Omega | volume = 5 | issue = 27 | pages = 16940–16943 | date = July 2020 | pmid = 32685863 | pmc = 7365549 | doi = 10.1021/acsomega.0c02208 | issn = 2470-1343 | url = }}{{cite journal | vauthors = Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DN, Naeem M, Sammeta VR, DeBoer S, Golen JA, Hulley EB, Stove CP, Chadeayne AR, Manke DR, Baumann MH | title = Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice | journal = ACS Pharmacol Transl Sci | volume = 5 | issue = 11 | pages = 1181–1196 | date = November 2022 | pmid = 36407948 | pmc = 9667540 | doi = 10.1021/acsptsci.2c00177 | url = }}{{cite journal | vauthors = Chue P, Andreiev A, Bucuci E, Els C, Chue J | title=A Review of Aeruginascin and Potential Entourage Effect in Hallucinogenic Mushrooms | journal=European Psychiatry | publisher=Royal College of Psychiatrists | volume=65 | issue=S1 | year=2022 | issn=0924-9338 | doi=10.1192/j.eurpsy.2022.2297 | doi-access=free | pages=S885| pmc=9568164 }}{{cite journal | vauthors = Glatfelter GC, Pham DN, Walther D, Golen JA, Chadeayne AR, Baumann MH, Manke DR | title = Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines | journal = ACS Omega | volume = 7 | issue = 28 | pages = 24888–24894 | date = July 2022 | pmid = 35874244 | doi = 10.1021/acsomega.2c03476 | pmc = 9301952 | url = }} 4-HO-TMT is closely related to bufotenidine, the N-trimethyl analogue of serotonin.

Like psilocin, 4-HO-TMT shows affinity for the serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2B receptors. However, its affinities for these receptors are lower than those of psilocin (by 8-, 6-, and 26-fold, respectively). Additionally, in another study, the {{Abbrlink|EC₅₀|half-maximal effective concentration}} value of 4-HO-TMT in activating the serotonin 5-HT_2A receptor was 324-fold lower than that of psilocin (6800 and 21{{nbsp}}nM, respectively). Similarly to psilocin, 4-HO-TMT does not bind to the serotonin 5-HT₃ receptor. This was in contrast to predictions, as the related compound bufotenidine is a strong and selective serotonin 5-HT₃ receptor agonist.

4-HO-TMT is a quaternary trimethyl ammonium compound, and as a result, is less likely to be able to cross the blood–brain barrier (BBB) and enter the central nervous system than other tryptamines. Accordingly, 4-HO-TMT showed no ability to cross an artificial BBB-like membrane in a study.{{cite journal | vauthors = Rakoczy RJ, Runge GN, Sen AK, Sandoval O, Wells HG, Nguyen Q, Roberts BR, Sciortino JH, Gibbons WJ, Friedberg LM, Jones JA, McMurray MS | title = Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms | journal = Br J Pharmacol | volume = 181 | issue = 19 | pages = 3627–3641 | date = October 2024 | pmid = 38825326 | doi = 10.1111/bph.16466 | url = | doi-access = free }} In rodents, 4-HO-TMT showed no head-twitch response (a behavioral proxy of psychedelic effects), hypolocomotion, or hypothermia, in contrast to psilocin and norpsilocin, but similarly to aeruginascin.

A synthetic prodrug of 4-HO-TMT, 4-AcO-TMT, has been developed. It is analogous to psilacetin (4-AcO-DMT), a prodrug of psilocin.