Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites.

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.