代谢物复杂的形成与细胞色素P450 orphenadrine。CYP2C11和CYP3A同功酶。

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鲁斯PH值,Mahnke A

代谢物复杂的形成与细胞色素P450 orphenadrine。CYP2C11和CYP3A同功酶。

生物化学杂志。1996年7月12日,52 (1):73 - 84。

PubMed ID

8678911 (在PubMed

]

文摘

表达和抑制细胞色素P450 (CYP)同功酶能够形成一个orphenadrine代谢物复杂研究微粒体治疗和inducer-treated雄性和雌性老鼠。高水平的complex-forming同功酶被发现在未经处理的雄性比雌性大鼠的微粒体。和几个P450抗病诱导剂治疗雄性老鼠没有显著增加体外形成复杂的程度。然而在雌性老鼠,苯巴比妥或地塞米松治疗导致明显的感应。复杂地层的同工酶特异性研究的几种方法,包括:1。抑制orphenadrine isozyme-specific P450的活动,如羟基化的睾丸激素,O-dealkylation的pentoxy-and ethoxyresorufin和复杂的形成与triacetyloleandomycin(道),2。由甲吡酮抑制orphenadrine复杂地层,道,和西咪替丁,3。相关的复杂水平与免疫化学,酶学、光谱方法确定数量的P450酶同功酶。我们的数据表明,CYP2C11, CYP3A同工酶和一位身份不明的P450物种与orphenadrine参与复杂的形成,但排除CYP1A1/2和CYP2B1/2的参与。CYP2C11形成代谢物的能力与orphenadrine复杂强烈建议有以下原因:1。 Efficient inhibition of testosterone 2 alpha- and 16 alpha-hydroxylation by complex formation with orphenadrine in microsomes of untreated male rats, 2. high expression of orphenadrine-complexing isozymes in untreated male compared to female rats, 3. specific inhibition of in vitro complex formation by cimetidine, 4. suppression of complex-forming isozymes by 3-methylcholanthrene and beta-naphthoflavone, and 5. concomitant induction of complex-forming isozymes, immunodetectable CYP2C11, and testosterone 2 alpha-hydroxylase by stanozolol. That at least one, but not all, CYP3A isozymes is involved in complex formation is concluded from inhibition experiments with TAO that show that orphenadrine complexation can be significantly inhibited in microsomes of dexamethasone-treated, but not in microsomes of untreated rats. Furthermore, complex formation with TAO is not inhibited by orphenadrine in microsomes of phenobarbital (PB)-treated rats. In PB-treated female rats, a further unidentified complex-forming isozyme can be detected that is not inhibited by complex formation with TAO.

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药物酶

药物	酶	类	生物	药理作用	行动
Orphenadrine	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂	细节