TY - JOUR T1 - Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 610 LP - 614 VL - 23 IS - 6 AU - L Y Lin AU - Y Kumagai AU - A Hiratsuka AU - S Narimatsu AU - T Suzuki AU - Y Funae AU - E W Distefano AU - A K Cho Y1 - 1995/06/01 UR - http://dmd.aspetjournals.org/content/23/6/610.abstract N2 - The 4-hydroxylation of S(+)- and R(-)-methamphetamine by rat liver microsomes was examined in Sprague-Dawley and Dark Agouti strains to determine the role of cytochrome P4502D (CYP2D) subfamily isozymes in catalyzing the reaction. In the study, anti-P450-BTL IgG, bufuralol, and quinine, a substrate and inhibitors of CYP2D isozymes, respectively, were found to block approximately 90% of the reaction as catalyzed by microsomes from Sprague-Dawley rats. Reconstituted systems of CYP2D isozymes purified from rat liver microsomes also mediated the reaction. These observations and the minimal activity found in microsomes from Dark Agouti rats support the notion that methamphetamine, like other phenylisopropylamine compounds, is oxidized on the 4-position of the aromatic ring by CYP2D isozymes. ER -