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苯环利定与其热解产物1-苯基环己烯之间的相互作用。

Interaction between phencyclidine and its pyrolysis product, 1-phenylcyclohexene.

作者信息

Chaturvedi A K, Kuntz D J

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105.

出版信息

Pharmacol Biochem Behav. 1988 Aug;30(4):1035-43. doi: 10.1016/0091-3057(88)90136-0.

DOI:10.1016/0091-3057(88)90136-0
PMID:3227028
Abstract

The interaction between phencyclidine (PCP) and its pyrolysis product, 1-phenylcyclohexene (PC), at metabolic level was evaluated in Swiss male mice (21-24 g). PC (1.1, 2.2 and 4.4 mmol/kg/day for 4 days, IP, in corn oil) treatment to mice induced the in vitro metabolism (p less than 0.05) of amidopyrine (17%), aniline (12%), phenacetin (62-100%), pentobarbital (20-26%), PCP (25-80%) and benzo[a]pyrene (81-147%) in the 9000 g liver fraction and the hepatic microsomal contents of cytochrome P-450 (18-42%). The induction of the mixed function oxygenase (MFO) system was consistent with the decreases in the concentrations of IP administered pentobarbital (0.27 mmol/kg, in saline) and PCP (16.4, 32.8 and 65.6 mumol/kg, in saline) in the serum, brain, liver and kidneys of PC pretreated mice. At 1 hr after the above doses of PC, the in vitro metabolism of amidopyrine, aniline, or phenacetin was not inhibited. However, the biotransformation of benzo[a]pyrene was inhibited by 33 to 45%. Though PC after a single dose did not alter the tissue concentrations of PCP, it increased the pentobarbital concentrations in the tissues studied (p less than 0.05). These results indicate that PC has a potential to induce the MFO system after the 4-day treatment. This property of PC plays an important role in the reduction of the action of PCP by enhancing its metabolism, thereby decreasing its tissue levels.

摘要

在21 - 24克的瑞士雄性小鼠中评估了苯环己哌啶(PCP)与其热解产物1 - 苯基环己烯(PC)在代谢水平上的相互作用。给小鼠腹腔注射PC(1.1、2.2和4.4毫摩尔/千克/天,共4天,溶于玉米油)后,9000克肝脏组分中氨基比林(17%)、苯胺(12%)、非那西丁(62 - 100%)、戊巴比妥(20 - 26%)、PCP(25 - 80%)和苯并[a]芘(81 - 147%)的体外代谢以及细胞色素P - 450的肝微粒体含量(18 - 42%)均有诱导作用(p < 0.05)。混合功能氧化酶(MFO)系统的诱导与PC预处理小鼠血清、脑、肝和肾中腹腔注射戊巴比妥(0.27毫摩尔/千克,溶于生理盐水)和PCP(16.4、32.8和65.6微摩尔/千克,溶于生理盐水)浓度的降低一致。在上述剂量的PC给药1小时后,氨基比林、苯胺或非那西丁的体外代谢未受抑制。然而,苯并[a]芘的生物转化受到33%至45%的抑制。虽然单次给药的PC未改变PCP的组织浓度,但它增加了所研究组织中戊巴比妥的浓度(p < 0.05)。这些结果表明,4天治疗后PC有诱导MFO系统的潜力。PC的这一特性通过增强PCP的代谢从而降低其组织水平,在减弱PCP的作用中发挥重要作用。

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