Spectral and inhibitory interactions of (+/-)-3,4-methylenedioxyamphetamine (MDA) and (+/-)-3,4-methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes.
Incubation of racemic methylenedioxyamphetamine (MDA) or methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes, in the presence of NADPH, generated a spectrally observed inhibitory complex with cytochrome P-450. The complex inhibited product formation from MDA and MDMA as well as other P-450 dependent reactions such as benzphetamine demethylation and CO binding. In the absence of NADPH, MDMA and MDA generated type I and type IIa difference spectra, respectively, suggesting differences in their binding to the enzyme active site. The N-demethylation of MDMA was partially inhibited by methimazole suggesting involvement of the hepatic flavin-containing monooxygenase.
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000661:Amphetamine / Q000378:metabolism; D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D001589:Benzphetamine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008694:Methamphetamine / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009249:NADP / Q000494:pharmacology; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D013053:Spectrophotometry
D000662:Amphetamines; D001589:Benzphetamine; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D009249:NADP; D008713:Methimazole; D003577:Cytochrome P-450 Enzyme System; D000661:Amphetamine; D010089:Oxidoreductases, N-Demethylating; D018817:N-Methyl-3,4-methylenedioxyamphetamine