sm-346 and Ventricular-Fibrillation

The influence of afobasol on threshold electrical fibrillation of the heart was studied in experiments on narcotized cats. It significantly elevated the cardiac fibrillation threshold in animals with intact myocardium and resembled class 1B anti-arrhythmic drug lidocaine in terms of this activity. Similar results were obtained using cats with denervated myocardium. These observations indicate that in the model of electrical fibrillation of the heart afobasol has marked antifibrillation action mediated through cardiomyocytes. This inference was confirmed by the studies of afobasol effects on cardiac rhythm variability in rats with acute myocardial ischemia. It is supposed that afobasol prevents cardiac fibrillation acting as an agonist of cytosolic sigma-1 receptors in cardiomyocytes

Topics: Animals; Anti-Arrhythmia Agents; Autonomic Denervation; Benzimidazoles; Cats; Female; Heart; Heart Rate; Male; Morpholines; Rats; Ventricular Fibrillation

Effect of afobazole on the threshold of electrical fibrillation of the heart was studied on anesthetized rats with intact myocardium. It was shown that the drug considerably increased the threshold of electrical fibrillation of the heart, being not inferior to reference class I antiarrhythmic drugs (lidocaine and procainamide) according to V. Williamse classification. Against the background of preliminary injection of σ-receptor antagonist haloperidol, afobazole exhibited no antifibrillatory activity. These findings and analysis of published reports suggest that antifibrillatory activity of afobazole is determined by its antagonistic influence on σ1-receptors localized in cardiomyocyte cytosol.

Topics: Animals; Anti-Arrhythmia Agents; Benzimidazoles; Haloperidol; Heart; Male; Morpholines; Myocytes, Cardiac; Rats; Receptors, sigma; Ventricular Fibrillation