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.

译文

:抗惊厥药对细胞色素P-450(17α,裂解酶)(CYP17),P-450arom(CYP19),P-450C21(CYP21),P-450SCC(CYP11A1)和P-450(11beta)活性的影响(CYP11B1)单加氧酶系统使用大鼠睾丸微粒体,人胎盘微粒体,牛肾上腺皮质微粒体,牛肾上腺皮质线粒体和纯化的细胞色素P-450(11beta)进行了研究。苯妥英钠,氯硝西am和卡马西平抑制了这些细胞色素P-450单加氧酶系统催化的类固醇生成,并确定了每种抗惊厥药的Ki值。乙内酰脲或丙戊酸钠均不抑制类固醇生成细胞色素P-450的活性。当在抗惊厥药存在下测量细胞色素P-450arom和P-450C21的活性时,苯妥英的Ki值(0.15 mM)接近于治疗条件下苯妥英的血浆浓度。苯妥英钠,氯硝西am和卡马西平直接抑制细胞色素P-450的单加氧酶活性,因为它们不影响NADPH-细胞色素P-450还原酶,NADPH-肾上腺铁氧还蛋白还原酶和肾上腺铁氧还蛋白的活性。

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