Calcium Channel Antagonists: Cardiovascular Selectivity of 1

The activities of a series of calcium antagonists including nife-dipine, verapamil, diltiazem and second-generation 1,4- dihy-dropyridines were determined in isolated vascular and cardiac preparations by tissue pharmacology and radioligand binding methods. The inhibitory effects against responses induced by 80 mM K depolarization in rat tail artery and against contrac-tions evoked in electrically paced rat papillary muscle were determined. Comparison of these IC50 values defines a vascu-lar/cardiac ratio as an index of relative activities in these tis-sues. Competition studies of the 1,4-dihydropyridines with rH]PN 200 1 10 binding in neonatal rat myocytes under polar-ized (5.8 mM K) and depolarized (50 mM K) states yields an index of voltage-dependent binding. The 1,4-dihydropyridine calcium antagonists exhibit significantly higher vascular/car