Boggan W O, Middaugh L D
Pharmacol Biochem Behav. 1987 Apr;26(4):671-6. doi: 10.1016/0091-3057(87)90594-6.
In vivo administration of phencyclidine (PCP) has been shown to enhance the accumulation of intravenously administered 3H quinuclidinyl benzilate (QNB) in certain regions of mouse brain. Since this effect can be blocked by prior administration of atropine, it has been interpreted as an enhancement by PCP of the specific binding of QNB. The present studies replicated this earlier work and determined that two major hydroxy metabolites of PCP found in rodents 1-(1-phenylcyclohexyl)4-hydroxy piperidine (4-OH-pip PCP) and 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (4-OH-cyclo PCP) probably do not contribute substantially to the PCP effect on QNB binding. Though QNB accumulation in brain was increased by injection of 4-OH-cyclo PCP, the doses necessary for the effect were substantially higher than those needed for PCP. Furthermore, pretreatment of the animals with beta-diethylaminoethyl diphenylpropylacetate (SKF525A), a compound known to block the metabolism of PCP in liver microsomes and thus the formation (at least in part) of these metabolites, did not attentuate the PCP effect on QNB binding.
体内给予苯环己哌啶（PCP）已被证明可增强静脉注射的3H-奎宁环基苯甲酸酯（QNB）在小鼠脑某些区域的蓄积。由于这种效应可被预先给予阿托品所阻断，因此被解释为PCP增强了QNB的特异性结合。本研究重复了这项早期工作，并确定在啮齿动物中发现的PCP的两种主要羟基代谢产物1-（1-苯基环己基）-4-羟基哌啶（4-OH-pip PCP）和1-（1-苯基-4-羟基环己基）哌啶（4-OH-cyclo PCP）可能对PCP对QNB结合的作用贡献不大。虽然注射4-OH-cyclo PCP可增加脑中QNB的蓄积，但产生这种效应所需的剂量远高于PCP所需的剂量。此外，用β-二乙氨基乙基二苯基丙基乙酸酯（SKF525A）预处理动物，该化合物已知可阻断肝微粒体中PCP的代谢，从而（至少部分地）阻断这些代谢产物的形成，但并未减弱PCP对QNB结合的作用。
