title: Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites.
abstract: 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.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma
chemical_list: D014150:Antipsychotic Agents; D010880:Piperidines; D011619:Psychotropic Drugs; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; C012134:SK&F 10047; C033114:3-hydroxyphencyclidine; C026539:preclamol; D010620:Phenazocine; D010622:Phencyclidine; D006220:Haloperidol