D'Amico G A, Kline R P, Maayani S, Weinstein H, Kupersmith J
Eur J Pharmacol. 1983 Apr 8;88(4):283-90. doi: 10.1016/0014-2999(83)90578-2.
The effects of phencyclidine [1-(1-phenylcyclohexyl)-piperidine; PCP] on cardiac action potential duration (APD) were compared to those of some of its derivatives, in strips of isolated frog ventricular muscle perfused with normal Ringer solution. We studied compounds with PCP-like behavioral actions (N-ethyl-1-phenyl-cyclohexylamine: PCE; and m-amino-PCP) as well as behaviorally inactive analogs (m-nitro-PCP; the quaternary derivative PCP-methyl iodide; and various fragments of the PCP molecule). Exposure to PCP, 3 microM to 1 mM, produced reversible, dose- and pH-dependent prolongations, of the APD to over 100% above control. The observed effects of the drugs are compatible with a mechanism of blockade of potassium conductance. An intracellular site for this action is suggested by: (i) the inactivity of the quaternary analog; (ii) the marked increase in the potency of the compounds when the external pH is changed in the region of their respective pKa values to increase the concentration of the unionized species; and (iii) the pronounced acceleration of the termination of the PCP effect by washout with a series of buffer solutions with decreasing pH values. The rank order of potency of the compounds in lengthening APD (PCE greater than m-amino PCP greater than PCP much much greater than m-nitro-PCP) is the same as reported from other pharmacological studies of specific PCP actions, and matches the rank of behavioral activity of the drugs.
在灌注正常林格液的离体青蛙心室肌条中，比较了苯环己哌啶[1-(1-苯基环己基)-哌啶；PCP]及其一些衍生物对心脏动作电位时程(APD)的影响。我们研究了具有PCP样行为作用的化合物（N-乙基-1-苯基环己胺：PCE；间氨基-PCP）以及行为无活性的类似物（间硝基-PCP；季铵衍生物PCP-甲基碘；以及PCP分子的各种片段）。暴露于3 microM至1 mM的PCP会使APD产生可逆的、剂量和pH依赖性延长，延长幅度超过对照的100%。观察到的药物作用与钾电导阻断机制相符。以下几点表明了该作用的细胞内位点：(i)季铵类似物无活性；(ii)当外部pH在其各自pKa值区域内改变以增加未电离物种的浓度时，化合物的效力显著增加；(iii)用一系列pH值降低的缓冲溶液冲洗可显著加速PCP作用的终止。化合物延长APD的效力顺序（PCE大于间氨基PCP大于PCP远大于间硝基PCP）与其他关于特定PCP作用的药理学研究报道相同，且与药物的行为活性顺序相符。
