The effects of N-(1-phenylcyclohexyl)piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 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. 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. 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. Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. 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. 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.
|Original language||English (US)|
|Number of pages||7|
|Journal||British Journal of Pharmacology|
|State||Published - 1982|
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