还原型氟哌啶醇氧化为氟哌啶醇：人P450IID6（司巴丁/异喹胍单加氧酶）的作用。
Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase).
作者信息
Tyndale R F, Kalow W, Inaba T
机构信息
Department of Pharmacology, University of Toronto, Canada.
出版信息
Br J Clin Pharmacol. 1991 Jun;31(6):655-60. doi: 10.1111/j.1365-2125.1991.tb05588.x.
Abstract
- The conversion of haloperidol (HAL) to reduced haloperidol (RHAL) and then back to HAL has been established in vivo and observed in psychiatric patients. The reduction of HAL to RHAL is known to be catalysed by a ketone reductase, while the nature of oxidation back to HAL is the subject of the present study. 2. We examined the in vitro oxidation of RHAL to HAL in human livers. The activity was microsomal and evidence is presented to suggest that the sparteine/debrisoquine metabolizing isoenzyme P450IID6 contributes to this oxidation. 3. Reciprocal inhibition studies between RHAL and sparteine, a specific substrate for cytochrome P450IID6, indicated that both compounds compete for the same binding site. Quinidine, the most specific inhibitor for this cytochrome P450 potently inhibited the oxidative conversion of reduced haloperidol to haloperidol. A significant correlation (rs = 0.62, P less than 0.01) was found between RHAL oxidation and sparteine oxidation in a study involving 17 human liver samples.
摘要
- 氟哌啶醇（HAL）转化为还原型氟哌啶醇（RHAL），然后再变回HAL的过程已在体内得到证实，并在精神病患者中观察到。已知HAL向RHAL的还原由一种酮还原酶催化，而氧化变回HAL的性质是本研究的主题。2. 我们研究了人肝脏中RHAL向HAL的体外氧化。该活性是微粒体的，并且有证据表明司巴丁/异喹胍代谢同工酶P450IID6参与了这种氧化。3. RHAL与细胞色素P450IID6的特异性底物司巴丁之间的相互抑制研究表明，这两种化合物竞争相同的结合位点。奎尼丁，这种细胞色素P450最特异性的抑制剂，强烈抑制还原型氟哌啶醇向氟哌啶醇的氧化转化。在一项涉及17个人肝脏样本的研究中，发现RHAL氧化与司巴丁氧化之间存在显著相关性（rs = 0.62，P小于0.01）。
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