Receptors for diphenylbutylpiperidine neuroleptics in brain, cardiac, and smooth muscle membranes. Relationship with receptors for 1,4-dihydropyridines and phenylalkylamines and with Ca2+ channel blockade.
Neuroleptic molecules of the diphenylbutylpiperidine series (DPBP), such as fluspirilene, penfluridol, pimozide and clopimozide, antagonize binding of (-)[3H]desmethoxyverapamil ((-)[3H]D888) and (+)[3H]PN 200-110 to rabbit brain, heart and smooth muscle membranes. The diphenylbutylpiperidine binding site in all these tissues is distinct but is allosterically related to the 1,4-dihydropyridine binding site and to the phenylalkylamine binding site. High and low affinity binding sites for (-)D888 were identified. (-)[3H]D888 binding at both types of sites was inhibited following the saturation of a single type of diphenylbutylpiperidine binding site. Half-maximal inhibition (K0.5) of brain, heart and smooth muscle membranes binding by different diphenylbutylpiperidines was in the range of 10-100 nM. These K0.5 values were one to two orders of magnitude higher than those found for the high affinity diphenylbutylpiperidine receptor in skeletal muscle membranes. The K0.5 values found in binding experiments in smooth muscle were similar to the (IC50) values for half-maximal inhibition by diphenylbutylpiperidine of voltage-dependent 45Ca2+ influx through the slow Ca2+ channel.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005484:Fluspirilene / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009130:Muscle, Smooth / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000031:analogs & derivatives / Q000378:metabolism
D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D011954:Receptors, Dopamine; D011978:Receptors, Nicotinic; C028051:neuroleptic receptor; C043184:4-desmethoxyverapamil; D005484:Fluspirilene; D014700:Verapamil; D002118:Calcium