Metabolism of methamphetamine, amphetamine and p-hydroxymethamphetamine by rat-liver microsomal preparations in vitro

Abstract

1. Methamphetamine N-demethylation and p-hydroxylation activities of rat liver were located mainly in the microsomal fraction.

2. The K_m values for methamphetamine and p-hydroxymethamphetamine demethyl-ations were 10 and 16mM, respectively. The K_m value for amphetamine p-hydroxylation was 10· μm; substrate inhibition occurred at high substrate concn. Two K_m values were obtained for the aromatic hydroxylation of methamphetamine (10·μM and 2·2mM).

3. 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.

4. The p-hydroxylation of methamphetamine and amphetamine in rats pretreated with phenobarbital, CoCl₂, SKF 525-A or iprindole were depressed.