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

S. Komori, T. Sawanobori, K. Tamura, K. A. Kane, J. R. Parratt

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino- 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 antiarrhythmic 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.

Original languageEnglish
Pages (from-to)193-200
Number of pages8
JournalJapanese Journal of Pharmacology
Volume65
Issue number3
Publication statusPublished - 1994

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Mexiletine
Disopyramide
Myocardial Reperfusion
Coronary Occlusion
Cardiac Arrhythmias
Coronary Vessels
Reperfusion
1-Butanol
Ventricular Premature Complexes
Ventricular Fibrillation
Ventricular Tachycardia
Pharmaceutical Preparations
Myocardial Infarction
4-isobutylamino-1,1-diphenyl-1-butanol maleate
Incidence

Keywords

  • AFD-19
  • Antiarrhythmic drug (class 1)
  • Arrhythmia (ischemia induced reperfusion induced)
  • NS2

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "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",
abstract = "We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino- 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 antiarrhythmic 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.",
keywords = "AFD-19, Antiarrhythmic drug (class 1), Arrhythmia (ischemia induced reperfusion induced), NS2",
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T1 - 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

T2 - Comparison with disopyramide and mexiletine

AU - Komori, S.

AU - Sawanobori, T.

AU - Tamura, K.

AU - Kane, K. A.

AU - Parratt, J. R.

PY - 1994

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N2 - We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino- 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 antiarrhythmic 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.

AB - We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino- 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 antiarrhythmic 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.

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