Pang K, Johnson S W, Maayani S, Freedman R
Pharmacol Biochem Behav. 1986 Jan;24(1):127-34. doi: 10.1016/0091-3057(86)90055-9.
The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.
本研究检测了苯环己哌啶[1-(1-苯基环己基)哌啶，PCP]及其三种类似物（间氨基-PCP、间硝基-PCP和PCP-甲基碘）对氨基甲酸乙酯麻醉大鼠小脑浦肯野神经元自发放电动作电位的抑制作用。腹腔注射和微量压力注射均用作给药途径。肠胃外给药后的相对效力与先前行为测试范式中的结果密切相符。PCP和间氨基-PCP效力相当，间硝基-PCP的效力低于PCP或间氨基-PCP，而PCP-甲基碘几乎没有活性。在对神经元进行局部给药后，间氨基-PCP的效力明显高于PCP，而PCP、间硝基-PCP和PCP-甲基碘效力相当。氚标记的PCP、间硝基-PCP和间氨基-PCP在小脑中具有相似的分布和代谢。PCP-甲基碘作为季铵离子，不能穿过血脑屏障。间硝基-PCP在pH 7.4时的离子化程度明显低于PCP或间氨基-PCP，因此可能更容易被脂质摄取。在采用肠胃外给药的实验中发现的PCP与其类似物之间的差异可能反映了药物分布的差异。当通过微量压力注射将这些药物直接注射到神经元上时，这些差异会最小化。
