Metabolism of methylenedioxymethamphetamine: formation of dihydroxymetham-phetamine and a quinone identified as its glutathione adduct

The in vitro conversion of (+)-3,4-methylenedioxymethamphe-tamine and (-)-3,4-methylenedioxymethamphetamine to the cor-responding catecholamine, 3,4-dihydroxymethamphetamine (N-methyl-a-methyldopamine), by rat liver microsomes was exam-med. Metabolite formation was monitored after short-term incu-bations using high-performance liquid chromatography-electro-chemical detection to determine concentrations of the cat-echolamine. The formation of N-methyl-a-methyldopamine exhibited enantioselectivity and levels were significantly higher after incubation of the (+)-isomer. The reaction appears to be cytochrome P-450 dependent as it was sensitive to SKF 525A and carbon monoxide. The catecholamine was unstable and was metabolized rapidly to a compound capable offorming an adduct with glutathione (GSH) and other thiol compounds. This second oxidation did not appear to be cytochrome P-450-dependent bu