Anti-arrhytmic and general pharmacological properties of some 1,3-benzodioxole derivatives.
Seven 1,3-benzodioxole derivatives have been found to be effective against certain types of experimentally induced arrhythmias. Among them, 2-[2-(5-chloro-2-methyl-1, 3-benzodioxol-2-yl)ethoxy]-N, N-diethyl-ethanamine (LR 529) showed to be the most active. LR 529 prevented arrhythmias induced by CaCl2 intoxication in anaesthetized and conscious rats, by benzene-epinephrine in anaesthetized guinea-pigs, and by direct electrical stimulation either at increasing intensity of the ventricles of anaesthetized cats or at increasing frequency of the rabbit isolated atria. The new compound reversed to sinus rhythm the arrhythmias provoked by intoxication with aconitine and ouabain respectively in anaesthetized rats and dogs. LR 529 (and the other 1,3-benzodioxoles as well) showed scant local anaesthetic activity, short-lasting hypotensive effects, not accompanied by any change in heart rate, and discrete anti-aggregating activity on rabbit platelets "in vitro". In general, the new compounds showed weak or no effect on autonomic and central nervous systems, neither influenced other pharmacological parameters (at least within the range of doses active on experimental arrhythmias). Acute toxicity studies have indicated that even if some of the 1,3-benzodioxoles were more toxic than quinidine and procainamide, their anti-arrhythmic indexes (especially those of LR 529) were greater than those of the two reference drugs.
D000779:Anesthetics, Local; D000818:Animals; D000889:Anti-Arrhythmia Agents; D004149:Dioxoles / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D004149:Dioxoles