Relative potencies of phencyclidine and analogs in the opiate receptor binding assay: Correlation with relative potencies determined in vivo in mouse and rat

Phencyclidine (PCP) and 15 analogs, precursors and metabolites were examined for their capacity to displace ³H-naloxone in the opiate receptor binding assay. The IC50 for PCP was 25 μM and IC50s for the analogs ranged from that of TCPY (7.1μM) to that of PCM (66μM). The three carbonitrile precursors of PCP analogs exhibited only very weak activity (IC50s > 3000 μM). These results were compared with those obtained with two in vivo tests for PCP-like activity. Rank orders of relative potencies in the opiate receptor binding assay were significantly correlated with rank orders of relative potencies obtained in the mouse rotarod test, as well as in the rat discriminative stimulus test. PCP also depressed the twitch height of the electrically stimulated guinea-pig ileum, another in vitro assay for opiate-like activity, but this effect was not reversed by naloxone up to a concentration of 5000 nM. It is suggested that although these interactions of PCP and analogs with standard opiate assays are not clearly defined mechanistically, the opiate receptor binding assay may serve as a simple preliminary method for comparing relative potencies of PCP analogs.