Vasodilating effects of the new calcium antagonist benidipine hydrochloride in anesthetized dogs and cats
Karasawa, A.; Kubo, K.; Shuto, K.; Oka, T.; Nakamizo, N.
Arzneimittel-Forschung 38(11a): 1707-1712
1988
ISSN/ISBN: 0004-4172 PMID: 3219145 Document Number: 319165
Vasodilating effects of a new 1,4-dihydropyridine derivative, (.+-.)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,-4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were investigated in anesthetized dogs and cats. Intravenous administrations of KW-3049 at doses of 0.3 to 10 .mu.g/kg exhibited a greater vasodilation in vertebral and coronary arteries than in common carotid and femoral arteries. The maximal effects of KW-3049 were equal to or more potent than those of nifedipine and nicardipine. Vertebral and coronary vasodilation following intravenous administration of 10 .mu.g/kg of KW-3049 continued for 240 min or more, whereas those following nifedipine or nicardipine (10 .mu.g/kg i.v.) disappeared within 30 min. A gradual and long-lasting increase of the vertebral and coronary blood flows following the intraduodenal administration of KW-3049 (0.1 mg/kg) was observed as compared with those of nifedipine (0.3 mg/kg i.d.) and nicardipine (0.3 mg/kg i.d.). When KW-3049 at a dose of 0.1 .mu.g/kg was intraarterially administered to vertebral or coronary arteries, the blood flow increased without affecting systemic blood pressure and its effects lasted longer than those of nifedipine and nicardipine (0.1 .mu.g/kg i.a.). In particular, the duration time in increase of coronary blood flow by KW-3049 was extremely longer, i.e. 11-fold and 6-fold those by nifedipine and nicardipine, respectively. Coronary vasodilating effect of KW-3049 was influenced neither by propranolol, atropine, diphenhydramine nor by aminophylline. Moreover, KW-3049 did not affect the vasodilator effect of adenosine. In conclusion, it was demonstrated that KW-3049 exhibits preferential coronary and cerebral vasodilating activity and the duration of its effects is consistently longer as compared with those of nifedipine and nicardipine.