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).^{[1][2][3][4][5]} 4-HO-TMT is closely related to bufotenidine, the N-trimethyl analogue of serotonin.^[1]

4-HO-TMT

Clinical data
Other names	4-OH-TMT; 4-hydroxy-N,N,N-trimethyltryptammonium; 4-Hydroxy-N,N,N-trimethyltryptamine; 4-HO-N,N,N-TMT; Dephosphorylated aeruginascin; Dephosphorylaeruginascin
Drug class	Serotonin receptor agonist
Identifiers
IUPAC name 2-(4-hydroxy-1H-indol-3-yl)ethyl-trimethylazanium
CAS Number	262285-41-6 Y
PubChem CID	17868117
ChemSpider	13318696
ChEBI	CHEBI:193061
Chemical and physical data
Formula	C13H19N2O+
Molar mass	219.308 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[N+](C)(C)CCC1=CNC2=C1C(=CC=C2)O
InChI 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

Like psilocin, 4-HO-TMT shows affinity for the serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2B 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-HT_2A 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]