Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct.

摘要: The in vitro conversion of (+)-3,4-methylenedioxymethamphetamine and (-)-3,4-methylenedioxymethamphetamine to the corresponding catecholamine, 3,4-dihydroxymethamphetamine (N-methyl-alpha-methyldopamine), by rat liver microsomes was examined. Metabolite formation monitored after short-term incubations using high-performance liquid chromatography-electrochemical detection determine concentrations catecholamine. N-methyl-alpha-methyldopamine exhibited enantioselectivity levels were significantly higher incubation (+)-isomer. reaction appears be cytochrome P-450 dependent as it sensitive SKF 525A carbon monoxide. catecholamine unstable metabolized rapidly a compound capable forming an adduct with glutathione (GSH) other thiol compounds. This second oxidation did not appear P-450-dependent but required NADPH microsomal protein. Catecholamine inhibited superoxide dismutase reducing agents. same product, characterized GSH adduct, could generated xanthine-xanthine oxidase mixture tyrosinase. Mass spectral data showed that 1:1 amine adduct. These results indicate MDMA is oxidized catechol quinone which or functions add. this its adducts may account for some irreversible actions on serotonergic neurons.