Cardiovascular effects of benidipine and amlodipine in isolated tissues and anesthetized dogs.
Benidipine and amlodipine, 1,4-dihydropyridine calcium channel blocking drugs, are long-acting antihypertensive and antianginal drugs. In the present study, the vascular-selectivity and duration of action of benidipine were determined in vitro and in vivo, and compared with those of amlodipine. The relaxing effect of benidipine on the canine coronary artery precontracted by KCl (55 mM) was about 40 times that of amlodipine. The negative inotropic effect of benidipine in the electrically-stimulated canine right ventricular papillary muscle was about twice that of amlodipine. The potency ratios of the vasorelaxing effect in the coronary artery and the negative inotropic effect in papillary muscle were 1300 for benidipine and 67 for amlodipine, respectively. In anesthetized dogs, the maximum hypotensive effect and the duration of action of 3 micrograms/kg (i.v.) benidipine was almost the same as those of 500 micrograms/kg (i.v.) amlodipine. The duration of the hypotensive action of benidipine at 10 micrograms/kg (i.v.) was almost the same as that of amlodipine at 1500 micrograms/kg (i.v.). Amlodipine at 1500 micrograms/kg (i.v.) reduced mean blood pressure and left ventricular dp/dt max immediately after its administration, whereas such transient falls were not observed after the administration of benidipine at 10 micrograms/kg (i.v.). These results suggest that benidipine possesses a stronger vasodilating effect and a higher vascular-selectivity, compared with amlodipine.
Moriyama
T
T
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; C061004:benidipine