The pharmacological specificity of representative psychotomimetic agents such as phencyclidine (PCP) analogs, opiate benzomorphans and several antipsychotic agents was assessed for the sigma and PCP binding sites. In a series of binding experiments, in rat brain membranes, sigma and PCP binding sites were labeled with [3H]-1-[1- (3-hydroxyphenyl) cyclohexyl] piperidine ([3H]PCP-3-OH), (+)[3H]-N-allylnormetazocine [(+)[3H]SKF 10047] and (+)[3H]-3-[3-hydroxy-phenyl]-N-(1-propyl)piperidine [(+)[3H]-3-PPP]. PCP analogs inhibit potently high affinity [3H]PCP-3-OH binding and (+)[3H]SKF 10047 binding, moderately the low affinity binding component of [3H]PCP-3-OH and very weakly (+)[3H]-3-PPP binding. (+)SKF 10047 and cyclazocine are potent to moderate inhibitors of (+)[3H]SKF 10047, high affinity [3H]PCP-3-OH and (+)[3H]-3-PPP binding, but extremely weak inhibitors of low affinity [3H]PCP-3-OH binding. The antipsychotic agents display high affinity for (+)[3H]-3-PPP binding sites, moderate affinity for (+)[3H]SKF 10047 sites and have no effect on either the high or low affinity [3H]PCP-3-OH binding. The present data further support the existence of multiple sigma and PCP binding sites.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)