Kammerer R C, Schmitz D A, Distefano E W, Cho A K
Drug Metab Dispos. 1981 May-Jun;9(3):274-8.
The in vitro metabolism of phencyclidine by rabbit liver 9000g supernatant fraction produces primarily three known hydroxylated metabolites-namely, 4-phenyl-4-piperidinocyclohexanol, 4-(4'-hydroxypiperdino)-4phenylcyclohexanol, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine-plus a new metabolite formed by oxidative scission of the piperidine ring yielding an aminoalcohol, and much smaller amounts of five unidentified metabolites. Incubation with 50% deuterium-labeled PCP indicates that these compounds are metabolites by monitoring the resulting doublets found in their mass spectra. The time, cofactor, and protein-dependent formation of these compounds confirms that they are indeed, metabolites. DPEA inhibits the production of the four quantitated metabolites with maximal I50 values of approximately 50 microM, implying the involvement of cytochrome P-450 in these reactions.
苯环利定在兔肝9000g上清液中的体外代谢主要产生三种已知的羟基化代谢物,即4-苯基-4-哌啶环己醇、4-(4'-羟基哌啶基)-4-苯基环己醇和1-(1-苯基环己基)-4-羟基哌啶,以及一种由哌啶环氧化裂解产生的氨基醇新代谢物,还有少量五种未鉴定的代谢物。与50%氘标记的苯环利定一起孵育表明,通过监测它们质谱中产生的双峰,这些化合物是代谢物。这些化合物的形成与时间、辅因子和蛋白质有关,证实它们确实是代谢物。二乙胺基乙醇(DPEA)抑制四种定量代谢物的产生,最大半数抑制浓度(I50)值约为50微摩尔,这意味着细胞色素P-450参与了这些反应。