Effect of an orally active Na+/H+ exchange inhibitor, SMP-300, on experimental angina and myocardial infarction models in rats.
The effects of SMP-300, an orally active, potent, and selective Na+/H+ exchange inhibitor, were evaluated and compared with those of nifedipine, propranolol, and nicorandil on three experimental angina models and on myocardial infarction in rats. SMP-300 (0.1-1 mg/kg, p.o.) reduced isoproterenol-induced ST segment depression in a dose-dependent manner. Its maximal effect was comparable to that reported for propranolol and greater than that of nifedipine. SMP-300 (0.3-1 mg/kg) reduced vasopressin-induced ST segment depression in a dose-dependent manner, and its maximal effect was comparable to those of nifedipine and nicorandil. SMP-300 (0.3-1 mg/kg, p.o.) and propranolol (100 mg/kg, p.o.) inhibited coronary artery occlusion-induced T-wave elevation, but nifedipine (3 mg/kg, p.o.) did not. SMP-300 (1 mg/kg, p.o.) reduced myocardial infarct size after 40 min of coronary artery occlusion followed by 24 h of reperfusion, but nifedipine (3 mg/kg, p.o.) or propranolol (100 mg/kg, p.o.) did not. This study provides support for the future use of a Na+/H+ exchange inhibitor as an anti-anginal drug with a novel mode of action.
Yamamoto
Setsuko
S
Research Center, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan. setukoy@sumitomopharm.co.jp
Matsui
Kazuki
K
Sasabe
Masao
M
Ohashi
Naohito
N
D000284:Administration, Oral; D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001392:Azocines / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications; D004562:Electrocardiography; D007545:Isoproterenol; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020108:Nicorandil / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D014667:Vasopressins
D001392:Azocines; D011758:Pyrroles; C419742:SMP-300; D017923:Sodium-Hydrogen Exchangers; D014665:Vasodilator Agents; D014667:Vasopressins; D020108:Nicorandil; D011433:Propranolol; D009543:Nifedipine; D007545:Isoproterenol