title: Antianginal effects of YM-16151-4 in various experimental angina models.
abstract: The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.
authors.affiliation: Medicinal Research Laboratories II, Yamanouchi Pharmaceutical Company, Ibaraki, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Shibasaki
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives; D000077770:Amifampridine; D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001127:Arginine Vasopressin; D001283:Atrioventricular Node / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000188:drug therapy; D004095:Dihydropyridines / Q000627:therapeutic use*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000627:therapeutic use; D009596:Nitrophenols / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011433:Propranolol / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D015221:Potassium Channels; C064876:YM 16151-1; D001127:Arginine Vasopressin; D011433:Propranolol; D015761:4-Aminopyridine; D009543:Nifedipine; D000077770:Amifampridine