Benzo [b]-promazines, chlorpromazine free radical and analino-N, N-dimethylpropylamine analogs influence rat striatal DA-adenylate cyclase and calmodulin-phosphodiesterase.
A series of Benzo [b]-promazines and analino-N, N-dimethylpropylamine analogs and the free radical of chlorpromazine were compared to chlorpromazine and promazine in the rat striatum for their ability to inhibit either dopamine activated adenylate cyclase or calmodulin stimulation of a partially purified high Km cyclic AMP phosphodiesterase. Chlorpromazine and the corresponding free radical were generally the most potent inhibitors of the two enzyme preparations, however, Piperazino-Benzo [b]-promazine, 1-Oxo-Benzo [b]-promazine, N-38-76-3A and Benzo [b]-promazine were relatively effective inhibitors. To a lesser extent, tyrosine, N-57-77, Piperidino-Benzo [b]-promazine, Diethyl-Benzo [b]-promazine, promazine and 1-Oxo-Diethyl-Benzo [b]-promazine exerted varying degrees of antagonism of the two enzymes. In all instances the compounds inhibited dopamine-sensitive adenylate cyclase to a greater extent than the calmodulin activated phosphodiesterase.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011395:Promazine / Q000031:analogs & derivatives / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D002147:Calmodulin; D005609:Free Radicals; D010640:Phenothiazines; D011437:Propylamines; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D011395:Promazine; D002746:Chlorpromazine; D004298:Dopamine