DISCRIMINANT EFFECTS OF BEHAVIORALLY ACTIVE AND INACTIVE ANALOGS OF PHENCYCLIDINE ON MEMBRANE ELECTRICAL EXCITABILITY

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (1) , 80-87
Abstract
The discriminant effects of several behaviorally active and inactive analogs of phencyclidine [PCP; 1-(phenylcyclohexyl) piperidine] and the actions of PCP and 3 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 .mu.M), a behaviorally active analog of PCP, increased action potential duration nearly 9-fold, blocked delayed rectification and at 0.5-1 .mu.M 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 .mu.M), 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 .mu.M) 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 PCP > TCP >>> P-F-PCP >>>> p-CH3-PCP = p-CH3O-PCP = p-Cl-PCP = p-NO2-PCP. Like PCP and its behaviorally active analogs, verapamil (50 .mu.M) and bepridil (50 .mu.M), 2 Ca-channel blockers, blocked delayed rectification in frog sartorius muscles whereas nifedipine (50 .mu.M), another Ca-channel blocker, did not. In crayfish skeletal muscle, PCP (50 .mu.M) increased and then depressed the Ca-dependent action potential without affecting other parameters. Nifedipine (50 .mu.M) and verapamil (25-100 .mu.M) reversibly blocked this Ca-dependent action potential. The discrimination by K-dependent mechanisms between behaviorally active and inactive analogs of PCP suggests that many of the behavioral alterations induced by PCP are likely due to an interaction with K channels in the central and peripheral nervous systems.