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EFFECTS OF PHENCYCLIDINE AND ITS DERIVATIVES ON ENTERIC NEURONES

1 The effects of N‐(1‐phenylcyclohexyl) piperidine (PCP) and related drugs on isolated intact segments of the guinea‐pig ileum were determined. 2 1–1‐(2‐Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea‐pig ileum. 3 Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone‐reversible component showed cross‐tolerance with morphine. 4 PCP pretreatment caused a shift to the right in the dose‐response curve to acetylcholine (ACh) that was not parallel with the control dose‐response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine‐like competitive fashion. 5 Binding sites for [3H]‐PCP were detected in homogenates of the guinea‐pig longitudinal muscle‐myenteric plexus preparation. 6 The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]‐PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. 7 These data suggest that the guinea‐pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.