Antianginal effects of YM430, a novel calcium entry-blocking and beta-adrenoceptor-blocking agent in several experimental angina models.
1. We evaluated the antianginal effects of YM430 in several experimental models in vitro and in vivo. 2. In isolated dog coronary artery, YM430 (10(-8)-10(-6) M) inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 59.2 nM. 3. In anesthetized rats, YM430 (10-100 mg/kg PO) inhibited arginine vasopressin-induced ST-segment depression with an IC50 value of 36.6 mg/kg PO. 4. In anesthetized dogs, YM430 (0.3 mg/kg IV) significantly inhibited ST-segment elevation induced by coronary artery occlusion. 5. These findings suggest that YM430 may be of value in the treatment of various types of angina pectoris such as variant and stable angina.
Shibasaki
K
K
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ibaraki, Japan.
Arai
Y
Y
Uchida
W
W
Okazaki
T
T
Asano
M
M
Takenaka
T
T
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000077770:Amifampridine; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology; D003329:Coronary Vasospasm / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology; D051381:Rats
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; C106124:YM 430; D011433:Propranolol; D015761:4-Aminopyridine; D009543:Nifedipine; D000077770:Amifampridine