Aromatic hydroxylation of methylenedioxybenzene (MDB) and methylenedioxymethamphetamine (MDMA) by rabbit liver microsomes.
1. Metabolites formed during incubation of methylenedioxybenzene (MDB) and methylenedioxymethamphetamine (MDMA) with rabbit liver microsomes were examined by h.p.l.c.-electrochemical detection and g.l.c.-mass spectrometry. 2. The trifluoroacetyl derivative of metabolite M-1, obtained from MDB, had a molecular ion at m/z 234 and was identified as 3,4-methylenedioxy-6-hydroxybenzene (sesamol) by comparison with authentic material. 3. The trifluoroacetyl derivative of metabolite M-2, obtained from MDMA, exhibited a molecular ion at m/z 401. Experiments with the deuterium substituted variants of MDMA indicated that the product was hydroxylated on the aromatic ring. 4. The formation of these hydroxylated metabolites required NADPH and was inhibited by carbon monoxide, indicating the possible participation of cytochrome P-450. Phenobarbital (PB) induction caused a marked enhancement of MDP hydroxylase activity whereas MDMA hydroxylation was not affected. 5. The aromatic hydroxylation of MDB and MDMA was also observed in a reconstituted system with cytochrome P-450 isozyme IIB4.
Kumagai
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Y
Department of Pharmacology, UCLA School of Medicine 90024.
Schmitz
D A
DA
Cho
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AK
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D052117:Benzodioxoles; D002248:Carbon Monoxide / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004149:Dioxoles / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D011199:Potentiometry; D011817:Rabbits
D052117:Benzodioxoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D004149:Dioxoles; D010636:Phenols; D015104:3,4-Methylenedioxyamphetamine; D009249:NADP; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; C025583:sesamol; D006899:Mixed Function Oxygenases; C040539:1,3-benzodioxole