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苯环己哌啶、氯胺酮、乙醇、苯巴比妥和异黄樟素对苯环己哌啶代谢的诱导作用。

Induction of phencyclidine metabolism by phencyclidine, ketamine, ethanol, phenobarbital and isosafrole.

作者信息

Kammerer R C, Schmitz D A, Hwa J J, Cho A K

出版信息

Biochem Pharmacol. 1984 Feb 15;33(4):599-604. doi: 10.1016/0006-2952(84)90314-9.

DOI:10.1016/0006-2952(84)90314-9
PMID:6704176
Abstract

The in vitro metabolism of phencyclidine (PCP) was investigated in 9000 g supernatant fractions of both control and PCP-, ketamine-, ethanol-, phenobarbital- or isosafrole-pretreated rats. Levels of PCP, trans-4-phenyl-4-piperidinocyclohexanol (I), 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (II), N-(5-hydroxypentyl)-1-phenylcyclohexylamine (IX), and 5-(1-phenylcyclohexylamino)-valeric acid (X) were monitored by gas chromatographic analysis in all cases. The inhibition of metabolism by N2, CO, SKF-525A or 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), or deletion of NADPH or protein, implied the involvement of cytochrome P-450 in the reactions. The various inducing agents affected the metabolism of PCP in different ways, implying that at least several isozymes of cytochrome P-450 were involved in the total metabolism. The majority of the consumed PCP was not accounted for by the measured metabolites so that some other metabolic pathways of major quantitative importance must be operative.

摘要

在对照大鼠以及经苯环利定(PCP)、氯胺酮、乙醇、苯巴比妥或异黄樟素预处理的大鼠的9000g上清液组分中研究了苯环利定(PCP)的体外代谢。在所有情况下,均通过气相色谱分析监测PCP、反式-4-苯基-4-哌啶环己醇(I)、1-(1-苯基环己基)-4-羟基哌啶(II)、N-(5-羟基戊基)-1-苯基环己胺(IX)和5-(1-苯基环己基氨基)戊酸(X)的水平。N2、CO、SKF-525A或2,4-二氯-6-苯氧基乙胺(DPEA)对代谢的抑制,或NADPH或蛋白质的缺失,表明细胞色素P-450参与了这些反应。各种诱导剂以不同方式影响PCP的代谢,这意味着细胞色素P-450的至少几种同工酶参与了总代谢。所消耗的大部分PCP无法通过所测代谢物来解释,因此一定存在其他一些具有重要定量意义的代谢途径。

相似文献

1
Induction of phencyclidine metabolism by phencyclidine, ketamine, ethanol, phenobarbital and isosafrole.苯环己哌啶、氯胺酮、乙醇、苯巴比妥和异黄樟素对苯环己哌啶代谢的诱导作用。
Biochem Pharmacol. 1984 Feb 15;33(4):599-604. doi: 10.1016/0006-2952(84)90314-9.
2
Species differences in the in vitro metabolism of phencyclidine.苯环利定体外代谢的种属差异。
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Metabolic-intermediate complex formation reveals major changes in rat hepatic cytochrome P-450 subpopulations in addition to those forms previously purified after phenobarbital, beta-naphthoflavone, and isosafrole induction.代谢中间复合物的形成揭示了大鼠肝脏细胞色素P-450亚群的主要变化,这些变化除了之前在苯巴比妥、β-萘黄酮和异黄樟素诱导后纯化出的那些形式之外。
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