Effects of NS-2, a new class 1 antiarrhythmic agent, and AFD-19, its active metabolite, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats: comparison with disopyramide and mexiletine.
We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino-1,1-diphenyl-1-butanol maleate) and AFD-19 (active metabolite of NS-2) on early stage ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized male rats. These effects were compared with those of disopyramide and mexiletine. Drugs were intravenously administered either before or after coronary occlusion. When administered 5 min before occlusion, 3 mg/kg of NS-2 and AFD-19 exhibited equivalent anti-arrhythmic activity to that of 5 mg/kg of disopyramide and mexiletine, as assessed by reductions in the number of premature ventricular complexes and in the incidences of ventricular tachycardia and ventricular fibrillation. In a dose of 5 mg/kg, the antiarrhythmic effects of NS-2 and AFD-19 were more pronounced. When administered 5 min after coronary artery occlusion, only NS-2 and AFD-19 (in doses of 5 mg/kg) had significant antiarrhythmic effects. None of the drugs influenced the severe ventricular arrhythmias induced by reperfusion when administered 1 min before reperfusion. In conclusion, NS-2 might be effective in reducing the severity of the life-threatening ventricular arrhythmias that occur during acute myocardial infarction.
Komori
S
S
Second Department of Internal Medicine, Yamanashi Medical College, Japan.
Sawanobori
T
T
Tamura
K
K
Kane
K A
KA
Parratt
J R
JR
D000605:Amino Alcohols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications; D004195:Disease Models, Animal; D004206:Disopyramide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000150:complications; D015425:Myocardial Reperfusion / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000188:drug therapy
D000605:Amino Alcohols; D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; C060006:AFD 21; C060007:4-isobutylamino-1,1-diphenyl-1-butanol maleate; D004206:Disopyramide