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Effect of an orally active Na+/H+ exchange inhibitor, SMP-300, on experimental angina and myocardial infarction models in rats.

Abstract
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.
AuthorsSetsuko Yamamoto, Kazuki Matsui, Masao Sasabe, Naohito Ohashi
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 39 Issue 2 Pg. 234-41 (Feb 2002) ISSN: 0160-2446 [Print] United States
PMID11791009 (Publication Type: Journal Article)
Chemical References
  • Azocines
  • Pyrroles
  • SMP-300
  • Sodium-Hydrogen Exchangers
  • Vasodilator Agents
  • Vasopressins
  • Nicorandil
  • Propranolol
  • Nifedipine
  • Isoproterenol
Topics
  • Administration, Oral
  • Angina Pectoris (chemically induced, drug therapy)
  • Animals
  • Azocines (pharmacology, therapeutic use)
  • Coronary Disease (complications)
  • Electrocardiography
  • Isoproterenol
  • Male
  • Myocardial Infarction (drug therapy, etiology, pathology)
  • Myocardial Reperfusion Injury (complications)
  • Myocardium (metabolism, pathology)
  • Nicorandil (pharmacology)
  • Nifedipine (pharmacology)
  • Propranolol (pharmacology)
  • Pyrroles (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Sodium-Hydrogen Exchangers (antagonists & inhibitors, metabolism)
  • Vasodilator Agents (pharmacology)
  • Vasopressins

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