Shannon H E, McQuinn R L, Vaupel D B, Cone E J
J Pharmacol Exp Ther. 1983 Feb;224(2):327-33.
The purpose of the present experiments was to evaluate the effects of eliminating or varying the size of the cycloalkyl ring of phencyclidine (PCP) from 3 to 8 carbons while leaving the composition of the benzene and piperidine rings unaltered. Compounds were evaluated for their effectiveness in producing PCP-like discriminative stimuli and changes in pupil diameter in the rat and impaired motor performance on the Rotarod in the mouse. All modifications of the cycloalkyl ring of PCP significantly reduced the relative potencies of the cycloalkyl analogs, shortened their duration of action and also modified their spectra of action, including their effectiveness in producing PCP-like discriminative stimuli and miosis in the rat as well as ataxia in the mouse. The present results demonstrate that the cyclohexyl moiety of PCP is an absolute requirement for producing a full PCP-like spectrum of activity.
本实验的目的是评估消除或改变苯环己哌啶(PCP)环烷基环的大小(从3个碳到8个碳),同时保持苯环和哌啶环的组成不变时所产生的影响。对化合物进行了评估,观察其在大鼠中产生类似PCP辨别刺激和瞳孔直径变化以及在小鼠中对转棒试验运动表现损害的有效性。PCP环烷基环的所有修饰均显著降低了环烷基类似物的相对效力,缩短了其作用持续时间,并改变了其作用谱,包括它们在大鼠中产生类似PCP辨别刺激和瞳孔缩小以及在小鼠中产生共济失调的有效性。目前的结果表明,PCP的环己基部分是产生完整的类似PCP活性谱的绝对必要条件。