In vitro O-demethylation of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane.
The possible relationship between metabolism and psychotomimetic activity among the methoxylated 1-phenyl-2-aminopropanes led to our investigation of the in vitro O-demethylation of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (1, DOM, STP). Employing a sensitive and highly selective stable isotope dilution assay, we observed that rabbit liver homogenates biotransform the amine 1 to its 2-O-demethyl, 5-O-demethyl, and bis (O-demethyl) metabolite metabolites. Both monophenolic metabolites are enriched in their S enantiomers. The bis(O-demethyl) metabolite has structural, chemical, and electrochemical similarites to the sympatholytic agent "6-hydroxydopamine". The possible significance of metabolic O-demethylation in terms of the psychotomimetic properties of amine 1 is discussed.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000138:chemical synthesis / Q000378:metabolism*; D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D003640:Dealkylation; D004563:Electrochemistry; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D013237:Stereoisomerism
D000662:Amphetamines; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine