Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Methylenedioxyamphetamine / analogs & derivatives
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3,4-Methylenedioxyamphetamine / metabolism*
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3,4-Methylenedioxyamphetamine / pharmacology
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Amphetamine / metabolism
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Amphetamines / metabolism*
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Animals
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Benzphetamine / metabolism
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Cytochrome P-450 Enzyme System / metabolism
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Kinetics
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Male
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Methamphetamine / metabolism
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Methimazole / pharmacology
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Microsomes, Liver / drug effects
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Microsomes, Liver / metabolism*
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N-Methyl-3,4-methylenedioxyamphetamine
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NADP / pharmacology
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Oxidoreductases, N-Demethylating / antagonists & inhibitors
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Oxidoreductases, N-Demethylating / metabolism
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Rats
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Spectrophotometry
Substances
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Amphetamines
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Benzphetamine
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Methamphetamine
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3,4-Methylenedioxyamphetamine
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NADP
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Methimazole
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Cytochrome P-450 Enzyme System
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Amphetamine
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Oxidoreductases, N-Demethylating
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N-Methyl-3,4-methylenedioxyamphetamine