4-AcO-MET, also known as metacetin, is a synthetic 4-acetoxy tryptamine related to 4-HO-MET. It contains an acetoxy group at the 4-position of the indole ring and a methyl-ethyl substitution on the terminal nitrogen. It has been described in analytical and pharmacological research, but there are no controlled human studies that establish its full clinical profile.
Chemistry and identification
4-AcO-MET is 4-acetoxy-N-methyl-N-ethyltryptamine. It is the acetate ester analogue of 4-HO-MET, also known as metocin. The compound is structurally related to 4-AcO-DMT, but the terminal nitrogen carries one methyl and one ethyl group rather than two methyl groups.
Crystallographic work has confirmed the solid-state structure of 4-AcO-MET fumarate. The study was part of a series examining psilacetin derivatives with altered terminal nitrogen substituents (Psilacetin derivatives: crystal structures of substituted analogues, 2021).
Receptor pharmacology
A 2023 study measured the activity of 4-AcO-MET at human 5-HT1A, 5-HT2A and 5-HT2C receptors and at the serotonin transporter. It showed agonist activity at 5-HT2A, with an EC50 of approximately 201 nM and an efficacy of about 40% relative to serotonin in the assay. These findings demonstrate receptor activity in a laboratory model, not a clinical effect in people (Kozell and colleagues, 2023).
Relationship to 4-HO-MET
The acetate group makes hydrolysis to 4-HO-MET chemically plausible. Reviews describe 4-AcO-MET as an acetate ester of 4-HO-MET, but detailed human pharmacokinetic evidence is lacking. The receptor study also found that the intact acetoxy compound was active, so conversion to the hydroxy analogue cannot be assumed to account for all biological activity.
Reported effects and toxicology
Descriptions of 4-AcO-MET are mostly anecdotal. A toxicology review notes reports of anxiety, paranoia, nausea and gastrointestinal discomfort, and records one post-mortem case in which 4-AcO-MET was detected alongside 4-HO-MET and 4-MeO-PCP. The presence of multiple substances means that the case does not establish 4-AcO-MET as the cause of death (Toxicology and analysis of psychoactive tryptamines, 2020).
No controlled human study has defined its acute toxic range, dependence potential or long-term effects. The receptor data do not establish clinical safety.
Related tryptamines
4-AcO-MET is related to 4-HO-MET, 4-AcO-DMT and 4-AcO-MiPT. Its mixed methyl-ethyl nitrogen substitution distinguishes it from the dimethyl and methyl-isopropyl analogues.
