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.
References
Sep 29, 1979·Biochimica Et Biophysica Acta·A Hiwatashi, Y Ichikawa
Jan 1, 1978·Methods in Enzymology·H W Strobel, J D Dignam
Jan 1, 1978·Methods in Enzymology·M KatagiriK Suhara
Apr 1, 1977·The Journal of Clinical Endocrinology and Metabolism·W JubizK G Tolman
Jul 13, 1976·Biochemistry·A HiwatashiK Aki
May 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·K KurokohchiY Ichikawa
Oct 1, 1991·The Journal of Steroid Biochemistry and Molecular Biology·S TomitaY Ichikawa
Jun 1, 1991·The Journal of Endocrinology·M J WheelerS Brown
May 31, 1990·European Journal of Pharmacology·W N Kühn-VeltenM R Müller
Nov 1, 1988·Journal of Steroid Biochemistry·A WadaM Okamoto
Oct 1, 1986·Journal of Biochemistry·T OhnishiM Okamoto
Jun 1, 1987·Archives of Disease in Childhood·B M MacardleC S Miller
Jul 1, 1987·Journal of the Royal Society of Medicine·M G Harrington, H M Hodkinson
Jun 1, 1974·Lancet·D Janz, D Schmidt
Sep 7, 1974·Lancet·H Laengner, K Detering
Nov 2, 1972·The New England Journal of Medicine·T J HahnJ G Haddad
Sep 1, 1983·Journal of Neurology, Neurosurgery, and Psychiatry·B K TooneR Grant
Sep 1, 1984·British Journal of Clinical Pharmacology·E PeruccaA Richens
Dec 1, 1984·Biochemical Pharmacology·H Vanden BosscheD Bellens
Jun 1, 1984·The Journal of Clinical Endocrinology and Metabolism·R S WeinsteinB B Gallagher
Jan 9, 1982·British Medical Journal·J Dana-HaeriA Richens
Mar 1, 1994·Annals of Internal Medicine·J French
Mar 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·C A LaughtonS Neidle
Apr 30, 1993·Science·M C Horowitz
Apr 1, 1956·Archives of Biochemistry and Biophysics·C MITOMAS UDENFRIEND
Citations
Jul 18, 2001·Neuroscience Letters·S BeyenburgB Stoffel-Wagner
Apr 27, 2001·Toxicology Letters·J F WaringR G Ulrich
Aug 5, 2000·Epilepsy Research·S BeyenburgB Stoffel-Wagner
Nov 5, 1999·Neuroreport·S BeyenburgC E Elger
Feb 26, 2000·Epilepsia·B Stoffel-WagnerC E Elger
Aug 24, 2010·Epilepsia·Kristine von KroghSteven Verhaegen
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
Jun 3, 2015·Translational Psychiatry·P W GoldS A Goldstein
Oct 16, 2013·Reproductive Toxicology·Rhayza Roberta AndrettaSandra M Miraglia
Aug 12, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yohei NishizatoSetsuko Komuro