Combined effects of benidipine and diltiazem in a rat model of experimental angina.
We examined the combined effects of the calcium channel blockers 1,4-dihydropyridine (benidipine) and benzothiazepine (diltiazem) on vasopressin-induced myocardial ischemia in anesthetized rats, an experimental model of angina. Benidipine (3, 10 microg/kg, i.v.) and diltiazem (300, 1000 microg/kg, i.v.) caused dose-related inhibition of vasopressin-induced S-wave depression, an index of myocardial ischemia. Co-administration of low doses of benidipine (3 microg/kg) and diltiazem (300 microg/kg) almost completely inhibited the S-wave depression, where the efficacy was similar to that obtained with the use of high doses of benidipine (10 microg/kg) or diltiazem (1000 microg/kg). These results suggest that the administration strategy employed may be useful in the treatment of angina pectoris.
Biomedical Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sunto, Shizuoka 411-8731, Japan. kozo.yao@kyowa.co.jp
Kozo
K
Yao
Shiro
S
Shirakura
D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001127:Arginine Vasopressin; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014662:Vasoconstrictor Agents
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C061004:benidipine; D004110:Diltiazem