Cardioprotective effect of TY-12533, a novel Na(+)/H(+) exchange inhibitor, on ischemia/reperfusion injury
| Autor: | Jun Sasamori, Kazuyuki Aihara, Takashi Sato, Susumu Satoh, Yusuke Mizuno, Kentaro Kogi, Sachiko Yoneyama, Akihiko Nagai, Fuminari Yamaguchi, Hiroaki Hisa, Tetsuo Kimura, Atsuo Takahashi, Fumiya Yoneyama |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Cardiotonic Agents Sodium-Hydrogen Exchangers Pyridines Sodium Aconitine Ischemia Myocardial Infarction Myocardial Ischemia chemistry.chemical_element Myocardial Reperfusion Injury Pharmacology Guanidines chemistry.chemical_compound In vivo Medicine Animals Platelet Sulfones Rats Wistar Cariporide business.industry Biological activity Arrhythmias Cardiac medicine.disease Rats Disease Models Animal chemistry Anesthesia business Reperfusion injury Anti-Arrhythmia Agents |
| Zdroj: | European journal of pharmacology. 404(1-2) |
| ISSN: | 0014-2999 |
| Popis: | The effects of 6,7,8, 9-tetrahydro-2-methyl-5H-cyclohepta[b]pyridine-3-carbonylguanidine maleate (TY-12533) on myocardial ischemia/reperfusion injury were evaluated in rats. Inhibitory effects of TY-12533, TY-50893 (the 9-chloro derivative of TY-12533) and cariporide on the platelet Na(+)/H(+) exchanger in vitro were almost equal at pH 6.2 and decreased at pH 6.7; but TY-12533 was four times more potent than TY-50893 and cariporide at pH 6.7. TY-12533, TY-50893 and cariporide administered before ischemia (0.01-1 mg/kg, i.v.) suppressed the ischemia/reperfusion-induced arrhythmias to the same extent in vivo; but TY-12533 was more effective than cariporide and TY-50893 when they were administered during ischemia (0.1-1 mg/kg). Similar results were obtained for the inhibitory effects of these drugs administered before ischemia (0.03-0.1 mg/kg, i.v.) and during ischemia (0.1-1 mg/kg) on the ischemia/reperfusion-induced myocardial infarction. These differences between TY-12533 and the other drugs in vitro and in vivo may be ascribed to the pK(a) values of the guanidinium moiety of TY-12533 (6.93), TY-50893 (6.35) and cariporide (6.28). |
| Databáze: | OpenAIRE |
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