Comparative structure-activity relationships for dihydropyridines as inhibitors of [3H]-nitrendipine binding vs cyclic nucleotide phosphodiesterases.
A comparison of the structure-activity relationships [SAR] for a number of compounds containing a dihydropyridine ring were investigated in vitro for the inhibition of [3H]-nitrendipine binding to membranes from rat ventricular muscle vs the inhibition of cyclic nucleotide phosphodiesterases [cNUC-PDE]. Although there were some gross similarities in the 2 SARs for these compounds, there were sufficient differences to indicate that these are 2 distinctly different biochemical properties of these compounds. Some of these compounds were relatively potent inhibitors of both cNUC-PDE and (3H)-nitrendipine binding. However, some analogs were potent inhibitors of one of the activities but relatively ineffective against the other activity. These data suggest that these 2 different biochemical mechanisms of action (and possibly others) may jointly influence the overall pharmacological profile of these compounds and indicate at least one reason why some of these compounds have different profiles of activity in vivo.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009568:Nitrendipine; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011725:Pyridines; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D009543:Nifedipine