Inhibition of 3H-nitrendipine binding in rat aortic and cerebral cortex membranes by the new dihydropyridine calcium antagonist benidipine hydrochloride.

Effects of a new calcium antagonist, benidipine hydrochloride (+/-)-(R*)-3-[(R*)-1-benzyl-3-piperidyl]methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedi carboxylate hydrochloride, KW-3049), on the 3H-nitrendipine binding in the rat aortic microsomes and cerebral cortex membranes were examined. The equilibrium dissociation constant (Kd) and the binding capacity (Bmax) were 0.32 nmol/l and 59.0 fmol/mg protein, respectively, in the rat aorta and 0.17 nmol/l and 450 fmol/mg protein, respectively, in the rat cortex. In both types of membranes, the specific binding was inhibited completely and concentration-dependently by six calcium antagonists such as benidipine, nicardipine, nisoldipine, nitrendipine, nifedipine and flunarizine. Diltiazem enhanced concentration-dependently the 3H-nitrendipine binding in the aortic and cortex membranes. Benidipine had the highest affinity for specific 3H-nitrendipine binding sites in the aorta (Ki = 0.063 nmol/l) and in the cortex membranes (0.043 nmol/l). The decreasing order of binding affinity of the isomers of benidipine for 3H-nitrendipine binding sites was S-S, benidipine, S-R, R-R and R-S. Presumed metabolites had a weak affinity for 3H-nitrendipine binding sites.