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Methamphetamine N-demethylation and p-hydroxylation activities of rat liver were located mainly in the microsomal fraction. The Km values for methamphetamine and p-hydroxymethamphetamine demethylations were 1.0 and 1.6 mM, respectively. The Km value for amphetamine p-hydroxylation was 10.2 microM; substrate inhibition occurred at high substrate concn. Two Km values were obtained for the aromatic hydroxylation of methamphetamine (10.6 microM and 2.2 mM). N-Demethylation of methamphetamine and p-hydroxymethamphetamine were depressed in rats pretreated with 3-methylcholanthrene, CoCl2 or SKF 525-A. In rats pretreated with phenobarbital, methamphetamine demethylase was induced and p-hydroxymethamphetamine demethylase was depressed. The p-hydroxylation of methamphetamine and amphetamine in rats pretreated with phenobarbital, CoCl2, SKF 525-A or iprindole were depressed.
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