Effect of palonidipine hydrochloride (TC-81), a new dihydropyridine derivative, on various myocardial ischemic models

• Published in: Nihon yakurigaku zasshi Vol. 102; no. 2; p. 85
• Main Authors: Kishimoto, T, Okamiya, Y, Aoki, K, Ota, M, Hoshina, K, Takeshita, T
• Format: Journal Article
• Language: Japanese
• Published: Japan 01.08.1993
• Subjects: Angina Pectoris - drug therapy; Angina Pectoris - physiopathology; Animals; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Dihydropyridines - pharmacology; Dihydropyridines - therapeutic use; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Electrocardiography - drug effects; Female; In Vitro Techniques; Male; Nifedipine - pharmacology; Nifedipine - therapeutic use; Rats; Rats, Wistar; Vasoconstriction - drug effects
• ISSN: 0015-5691
• DOI: 10.1254/fpj.102.85

The antianginal effects of palonidipine, a novel 1,4-dihydropyridine derivative, and nifedipine on various myocardial ischemic models were compared. (1) Palonidipine at 0.5 mg/kg, p.o. significantly inhibited vasopressin-induced ST depression of ECG in Donryu rats. This activity was about 5 times more potent than that of nifedipine and was long-lasting. (2) Palonidipine at 1 mg/kg, i.d. significantly inhibited ST depression induced by isoproterenol in Wistar rats. This activity of TC-81 was more potent than that of nifedipine. (3) Palonidipine at 3 micrograms/kg, i.v. produced an increase in regional myocardial tissue blood flow in the ischemic region of chronic coronary artery occluded dogs. (4) In isolated dog coronary artery, palonidipine at a concentration of 10(-10) M or greater inhibited the amplitude of 3,4-DAP-induced cyclic contractions in a concentration-dependent manner. This activity was 10-30 times more potent than that of nifedipine. (5) An intracoronary injection of endothelin (30 pmol/kg) reduced the coronary blood flow, subepicardial tissue blood flow, and subepicardial pH in anesthetized dogs. The ST elevation of ECG over 0.1 mV also occurred in 8 of 10 cases. In all the cases, ventricular extrasystoles were noted, and 9 out of 10 animals died. Pretreatment with palonidipine (3 micrograms/kg, i.v.) inhibited endothelin-induced ischemic changes, with a potency greater than that of nifedipine. These results suggest that palonidipine may be useful for the therapy of angina-pectoris.