Antiarrhythmic effects of MS-551, a new class III antiarrhythmic agent, on canine models of ventricular arrhythmia.
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.
Kamiya
J
J
Department of Pharmacology, Mitsui Pharmaceuticals, Inc., Chiba, Japan.
Ishii
M
M
Katakami
T
T
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004071:Digitalis Glycosides; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology*; D013610:Tachycardia / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D004071:Digitalis Glycosides; D011744:Pyrimidinones; C076259:nifekalant