Enzymic and chemical demethylenation of (methylenedioxy)amphetamine and (methylenedioxy)methamphetamine by rat brain microsomes
Chemical Research in Toxicology May 1, 1992 L.y. Lin, Yoshito Kumagai, Arthur K. Cho 67 citations
Rat brain microsomes convert MDA and MDMA into dihydroxyamphetamine (DHA) and dihydroxymethamphetamine (DHMA), respectively. This demethylenation requires NADPH and is strongly inhibited by carbon monoxide/oxygen, indicating involvement of cytochrome P450. The process is inhibited by desipramine, imipramine, and methimazole but not by SKF-525A or alpha-naphthoflavone. Biphasic Lineweaver-Burk plots suggest multiple isozymes may be involved, and no significant stereoselectivity is observed. Catechol formation is 2.6 times greater in phosphate buffer than HEPES buffer, but this difference disappears with desferal and hydroxyl radical scavengers. Sensitivity to catalase and stimulation by ferric ion and EDTA indicate both a cytochrome P450-mediated component and a chemical component involving hydroxyl radicals.