Yamada K, Matsui K, Satoh K, Kitano M, Yamamoto S, Ohashi N
Sumitomo Pharmaceuticals Co., Ltd., Research Center 1-98 Kasugadenaka 3-chome, Konohana-ku, 554-0022, Osaka, Japan.
Eur J Pharmacol. 2000 Sep 15;404(1-2):201-12. doi: 10.1016/s0014-2999(00)00610-5.
The effects of N-(aminoiminomethyl)-1, 4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid (SM-20550), a novel potent Na(+)/H(+) exchanger, and nicorandil, a K(+) channel opener with nitrate-like activity, were studied in a myocardial ischemia and reperfusion injury model. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). Intravenous administration of SM-20550 before ischemia reduced the infarct size by approximately 30-70% in a dose-dependent manner, with a significant reduction in serum creatine phosphokinase activity. Similarly, intravenous administration of nicorandil before ischemia reduced the infarct size by 33% with a significant reduction in serum creatine phosphokinase activity. Moreover, intravenous administration of SM-20550 after ischemia resulted in a significant, approximately 20-40% reduction in the infarct size, but the administration of nicorandil after ischemia did not reduce the infarct size. These results indicate that SM-20550 reduced myocardial necrosis when administered either before or after ischemia.
