Abstract

The discriminant effects of several behaviorally active and inactive analogs of phencyclidine [PCP; 1-(phenylcyclohexyl) piperidine] and the actions of PCP and three Ca-channel antagonists were examined on electrical excitability in frog and crayfish skeletal muscles. In frog sartorius muscle, 1-[1-(2-thienylcyclohexyl)piperidine (TCP; 100 microM), a behaviorally active analog of PCP, increased action potential duration nearly 9-fold, blocked delayed rectification and at 0.5 to 1 microM also increased the quantal release of transmitter. A partial blockade of delayed rectification and slight prolongation of the action potential occurred with 1-(p-fluorophenylcyclohexyl)piperidine (p-F-PCP; 100 microM), which possesses about 25% of the behavioral activity of PCP. Of the remaining p-phenyl- substituted analogs which never exhibited more than 10% of the behavioral potency of PCP, only 1-(1-p-nitrophenylcyclohexyl)piperidine (p-NO2-PCP; 100 microM) produced a frequency-dependent prolongation of the action potential but, like the p-methoxy-, p-chloro- and p-methyl- analog, it did not block delayed rectification. The order of potencies of these analogs in blocking delayed rectification, prolonging the muscle action potential and in affecting alternation impairment and response rate depression is therefore: PCP much greater than TCP greater than p-F-PCP much greater than p-CH3-PCP = p-CH3O-PCP = p-Cl-PCP = p-NO2-PCP. Like PCP and its behaviorally active analogs, verapamil (50 microM) and bepridil (50 microM), two Ca-channel blockers, also blocked delayed rectification in frog sartorius muscles whereas nifedipine (50 microM), another Ca-channel blocker, did not.(ABSTRACT TRUNCATED AT 250 WORDS)