sm-346 and Arrhythmias--Cardiac

Afobasol caused insignificant dose-related decrease of main parameters of cardiac activity in narcotized animals and was similar to pulse-decelerating calcium antagonists in terms of hemodynamic effects. Reperfusion after acute regional myocardial ischemia induced malignant cardiac rhythm disorders and progressive impairment of cardiac pump function. These changes combined with increased peripheral resistance created conditions for the development of cardiac insufficiency. Afobasol administered 5 min before the onset of reperfusion significantly reduced the frequency and intensity of cardiac rhythm disturbances and thereby prevented cardiac insufficiency. It is conjectured that cardioprotectice action of afobasol in these conditions was due to its ability to activate sigma-1 receptors in cardiomyocytes and thereby protected heart cells from excessive accumulation of Ca2+ ions.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzimidazoles; Calcium Channel Blockers; Cats; Female; Hemodynamics; Male; Morpholines; Myocardial Reperfusion Injury

Experiments on conscious male rats have shown that, under conditions of the aconitine-induced arrhythmia model, afobazole and other 2-mercaptobensimidazole derivatives exhibit antiarrhythmic effect, i.e. possess properties of rapid Na+ channel antagonists. The effect of afobazole under these conditions was significantly more pronounced than that of the reference drugs lidocaine and procainamide. The antiarrhythmic (antifibrillatory) effect of afobazole was also detected under the conditions of arrhythmia caused by high doses of calcium chloride. This drug was 1.5 times more effective in its antifibrillatory action than lidocaine, but it was less effective than verapamil. It has been also found that afobazole possesses a wider therapeutic spectrum than the well-known antiarrhythmic drugs of class I and IV (lidocaine, procainamide, ethmosine and verapamil).

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzimidazoles; Calcium Chloride; Male; Morpholines; Rats; Sodium Channel Blockers; Structure-Activity Relationship