4-HO-TMT

4-HO-TMT
Clinical data
Other names4-OH-TMT; 4-Hydroxy-N,N,N-trimethyltryptamine; 4-HO-N,N,N-TMT; Dephosphorylated aeruginascin; Dephosphorylaeruginascin
Drug classSerotonin receptor agonist
Identifiers
  • 2-(4-hydroxy-1H-indol-3-yl)ethyl-trimethylazanium
PubChem CID
ChemSpider
ChEBI
Chemical and physical data
FormulaC13H19N2O+
Molar mass219.308 g·mol−1
3D model (JSmol)
  • C[N+](C)(C)CCC1=CNC2=C1C(=CC=C2)O
  • InChI=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
  • Key:RMPOMMZKJNCOTM-UHFFFAOYSA-O

4-HO-TMT, or 4-OH-TMT, also known as 4-hydroxy-N,N,N-trimethyltryptamine 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).[1][2][3][4][5] 4-HO-TMT is closely related to bufotenidine, the N-trimethyl analogue of serotonin.[1]

Like psilocin, 4-HO-DMT shows affinity for the serotonin 5-HT1A, 5-HT2A, and 5-HT2B receptors.[1][5][4] However, its affinities for these receptors are lower than those of psilocin (by 8-, 6-, and 26-fold, respectively).[1][5][4] Additionally, in another study, the EC50Tooltip half-maximal effective concentration value of 4-HO-TMT in activating the serotonin 5-HT2A receptor was 324-fold lower than that of psilocin (6800 and 21 nM, respectively).[2] Similarly to psilocin, 4-HO-TMT does not bind to the serotonin 5-HT3 receptor.[1] This was in contrast to predictions, as the related compound bufotenidine is a strong and selective serotonin 5-HT3 receptor agonist.[1]

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.[1][4] Accordingly, 4-HO-TMT showed no ability to cross an artificial BBB-like membrane in a study.[2] 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.[3]

A synthetic prodrug of 4-HO-TMT, 4-AcO-TMT, has been developed.[1][5] It is analogous to psilacetin (4-AcO-DMT), a prodrug of psilocin.[1][5]

  1. ^ a b c d e f g h i Chadeayne AR, Pham DN, Reid BG, Golen JA, Manke DR (July 2020). "Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity". ACS Omega. 5 (27): 16940–16943. doi:10.1021/acsomega.0c02208. ISSN 2470-1343. PMC 7365549. PMID 32685863.
  2. ^ a b c Rakoczy RJ, Runge GN, Sen AK, Sandoval O, Wells HG, Nguyen Q, et al. (October 2024). "Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms". Br J Pharmacol. 181 (19): 3627–3641. doi:10.1111/bph.16466. PMID 38825326.
  3. ^ a b Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DN, et al. (November 2022). "Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice". ACS Pharmacol Transl Sci. 5 (11): 1181–1196. doi:10.1021/acsptsci.2c00177. PMC 9667540. PMID 36407948.
  4. ^ a b c d Chue P, Andreiev A, Bucuci E, Els C, Chue J (2022). "A Review of Aeruginascin and Potential Entourage Effect in Hallucinogenic Mushrooms". European Psychiatry. 65 (S1). Royal College of Psychiatrists: S885. doi:10.1192/j.eurpsy.2022.2297. ISSN 0924-9338. PMC 9568164.
  5. ^ a b c d e Glatfelter GC, Pham DN, Walther D, Golen JA, Chadeayne AR, Baumann MH, et al. (July 2022). "Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines". ACS Omega. 7 (28): 24888–24894. doi:10.1021/acsomega.2c03476. PMC 9301952. PMID 35874244.