title: Comparison of inhibitory actions of chlorpromazine or its 7,8-dihydroxy and 7,8-dioxo-didesmethyl analogs on DA-sensitive adenylate cyclase and calmodulin activation of phosphodiesterase in rat striatum.
abstract: Two chlorpromazine analogs, 7,8-diOH- and 7,8-dioxo-didesmethyl-chlorpromazine were compared to chlorpromazine (CPZ) with regard to inhibition of three parameters of enzyme activity in rat striatum: 1) dopamine + GTP-sensitive adenylate cyclase in homogenates; 2) dopamine, GTP, calmodulin and Ca++-sensitive adenylate cyclase in washed particulate fractions; and 3) calmodulin-Ca++ activation of high Km cyclic AMP dependent phosphodiesterase in dialyzed supernatant fractions. Chlorpromazine was clearly the most potent antagonist in all three experimental conditions. The CPZ derivatives displayed greatest potency on the particulate adenylate cyclase and all three drugs were 1 to 2 orders of magnitude more effective as inhibitors of the adenylate cyclase preparations than with the calmodulin-Ca++ phosphodiesterase.
authors.forename: G C
authors.initials: GC
authors.lastname: Palmer
authors.forename: K A
authors.initials: KA
authors.lastname: Pajer
authors.forename: A A
authors.initials: AA
authors.lastname: Manian
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D006160:Guanosine Triphosphate; C045529:7,8-dihydroxy-N,N-didesmethylchlorpromazine; C045530:7,8-dioxo-N,N-didesmethylchlorpromazine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D002118:Calcium; D002746:Chlorpromazine; D004298:Dopamine