Vasodilating effects of the new calcium antagonist benidipine hydrochloride in anesthetized dogs and cats.
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 micrograms/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 micrograms/kg of KW-3049 continued for 240 min or more, whereas those following nifedipine or nicardipine (10 micrograms/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 micrograms/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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kubo
K
K
Shuto
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; C050883:benidipine hydrochloride; D009529:Nicardipine; D010208:Papaverine; D009543:Nifedipine