PMID: 9182861Jan 1, 1997Paper

Direct inhibitions of the activities of steroidogenic cytochrome P-450 mono-oxygenase systems by anticonvulsants

The Journal of Steroid Biochemistry and Molecular Biology
T Ohnishi, Y Ichikawa

Abstract

The effects of anticonvulsants on the activities of cytochromes P-450(17alpha,lyase) (CYP17), P-450arom (CYP19), P-450C21 (CYP21), P-450SCC (CYP11A1), and P-450(11beta) (CYP11B1) mono-oxygenase systems were studied using rat testicular microsomes, human placental microsomes, bovine adrenocortical microsomes, bovine adrenocortical mitochondria and purified cytochrome P-450(11beta). Phenytoin, clonazepam and carbamazepine inhibited the steroidogenesis catalysed by these cytochrome P-450 mono-oxygenase systems and the Ki values for each anticonvulsant were determined. Neither hydantoin nor sodium valproate inhibited the activities of steroidogenic cytochromes P-450. When the activities of cytochromes P-450arom and P-450C21 were measured in the presence of anticonvulsants, the Ki values (0.15 mM) for phenytoin were close to the plasma concentration of phenytoin under therapeutic conditions. Phenytoin, clonazepam and carbamazepine directly inhibited the monooxygenase activities of cytochromes P-450, because they did not affect the activities of NADPH-cytochrome P-450 reductase, NADPH-adrenoferredoxin reductase and adrenoferredoxin.

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Citations

Jul 18, 2001·Neuroscience Letters·S BeyenburgB Stoffel-Wagner
Oct 26, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·N W JacobsenF K Birkved
Jul 2, 2009·Acta Neurologica Scandinavica. Supplementum·M W GustavsenS Verhaegen
Aug 12, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yohei NishizatoSetsuko Komuro

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