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.
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Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine; D009568:Nitrendipine