4-HO-TMT

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). 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 EC₅₀Tooltip 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 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. 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.