title: The pharmacological differences in antianginal effects of long-lasting calcium channel blockers: azelnidipine and amlodipine.
abstract: We examined antianginal effects of azelnidipine and amlodipine in an arginine vasopressin-induced rat anginal model. Oral administration of azelnidipine or amlodipine produced long lasting inhibition of arginine vasopressin-induced ST-segment depression in electrocardiogram. The degrees of inhibition with azelnidipine at doses of 1 and 3 mg/kg were comparable to those with amlodipine at 3 and 10 mg/kg. Both drugs lowered mean blood pressure in a dose-related manner, whereas only azelnidipine decreased heart rate. Azelnidipine at 3 mg/kg and amlodipine at 10 mg/kg produced a similar decrease in the rate pressure product, an index for cardiac oxygen consumption. Their inhibitory effects on calcium-induced vascular contraction were compared in isolated porcine coronary arteries. Both drugs produced a slow-developing inhibition of calcium-induced contraction. Although their inhibitory effects were similar, the way the both drugs inhibited calcium-induced contraction differed with each other. After removing the drug from bathing solution, the inhibitory effects of azelnidipine were not blunted but were sustained for a long time, which indicates that azelnidipine has high vascular affinity. On the other hand, those of amlodipine were rapidly blunted. These results suggest that the mechanisms underlying antianginal effects of azelnidipine differ from those of amlodipine. The antianginal effect with azelnidipine may be accounted for by its high affinity to the coronary blood vessels and the heart rate slowing effect, both of which are not shared with amlodipine.
authors.affiliation: Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. fujisawa.michio.ec@daiichisankyo.co.jp
authors.forename: Michio
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Yorikane
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koike
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001127:Arginine Vasopressin; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013552:Swine; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001127:Arginine Vasopressin; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine; D002118:Calcium