Antiarrhythmic effects of MS-551, a new class III antiarrhythmic agent, on canine models of ventricular arrhythmia.

Abstract

The antiarrhythmic effects of MS-551, which prolongs cardiac action potential duration without affecting the maximum upstroke velocity of the action potential, were assessed in three different canine ventricular arrhythmia models: 1) ventricular tachycardia (VT) induced by electrical stimuli 3-5 days after myocardial infarction, 2) spontaneous ventricular tachyarrhythmias 24-48 hr after two-stage coronary ligation and 3) ventricular tachyarrhythmias induced by digitalis. Intravenous administration of MS-551 (0.1-1 mg/kg) decreased the susceptibility in 10 dogs out of 13 to VT or ventricular fibrillation evoked by programmed electrical stimulation (PES) delivered to the ventricular septum 3-5 days after myocardial infarction. Oral administration of MS-551 (3 mg/kg) also decreased the susceptibility to VT evoked by PES in 7 out of 10 conscious postinfarction dogs. Concurrently, intravenous (0.1-1 mg/kg) or oral (3 mg/kg) administration of MS-551 produced increases in the ventricular effective refractory periods (ERP) by 7 +/- 1% - 17 +/- 3% or 13 +/- 2%, respectively. Similarly, d-sotalol (0.3-3 mg/kg, i.v. and 10 mg/kg, p.o.) decreased the susceptibility to VT with increased ERP. However, MS-551 (1 and 10 mg/kg, i.v.) failed to inhibit both canine two-stage coronary ligation arrhythmia and digitalis arrhythmia. These results suggest that MS-551 is a pure class III antiarrhythmic drug which may be effective in the treatment of life-threatening reentrant tachyarrhythmias, but not in automaticity arrhythmias.

• Authors: J Kamiya, M Ishii, T Katakami
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 58 Issue 2 Pg. 107-15 (Feb 1992) ISSN: 0021-5198 [Print] Japan
• PMID: 1507517 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Digitalis Glycosides
• Pyrimidinones
• nifekalant

Topics

• Administration, Oral
• Animals
• Anti-Arrhythmia Agents (administration & dosage, pharmacology)
• Digitalis Glycosides
• Disease Models, Animal
• Dogs
• Electric Stimulation
• Electrocardiography (drug effects)
• Female
• Heart Rate (drug effects)
• Injections, Intravenous
• Male
• Pyrimidinones (administration & dosage, pharmacology)
• Tachycardia (drug therapy)