Cho A K, Hiramatsu M, Schmitz D A, Nabeshima T, Kameyama T
Department of Pharmacology, UCLA School of Medicine 90024-1735.
Pharmacol Biochem Behav. 1991 Aug;39(4):947-53. doi: 10.1016/0091-3057(91)90058-a.
The pharmacodynamics and pharmacokinetics of three phencyclidine analogs, differing from phencyclidine (PCP) only in the nature of the amine structure, were determined after intravenous doses of equimolar amounts to rats. The purpose of the study was to assess the role of pharmacokinetics in the in vivo potency of the compounds. The compounds examined were phenylcyclohexyl-pyrrolidine (PCPY), diethylamine (PCDE), ethylamine (PCE), and phencyclohexylamine (PCA). The behavior responses monitored included ataxia and others previously shown to be characteristic of PCP. In contrast to their relative affinities for the MK 801 binding site, the behavioral potencies of PCE, PCDE and PCPY were comparable to PCP. The major discrepancy occurred with PCDE, whose affinity for the NMDA receptor was 1/20th of PCP. The pharmacokinetic studies showed that the discrepancy between in vivo and in vitro activity of PCDE could be partially accounted for by its conversion to PCE, a relatively potent PCP-like agent.
给大鼠静脉注射等摩尔量的三种仅在胺结构性质上与苯环利定（PCP）不同的苯环利定类似物后，测定了它们的药效学和药代动力学。该研究的目的是评估药代动力学在这些化合物体内效力中的作用。所检测的化合物有苯基环己基吡咯烷（PCPY）、二乙胺（PCDE）、乙胺（PCE）和苯基环己胺（PCA）。监测的行为反应包括共济失调以及先前显示的其他PCP特征性反应。与它们对MK 801结合位点的相对亲和力相反，PCE、PCDE和PCPY的行为效力与PCP相当。主要差异出现在PCDE上，其对NMDA受体的亲和力是PCP的1/20。药代动力学研究表明，PCDE体内和体外活性之间的差异可部分归因于其转化为PCE，一种相对强效的类PCP药物。
