Ethyl-3-ethoxycarbonyl-4-hydroxy-2 H-1,2-benzothiazine-2-acetate-1,1-dioxide, a compound producing ventricular arrhythmias

Abstract

Ethyl-3-ethoxycarbonyl-4-hydroxy-2 H-1,2-benzothiazine-2-acetate-1,1-dioxide (McN-2165), 5 mg/kg iv, administered to anesthetized dogs, consistently produced an increase in the QRS interval and venticular ectopic beats. These effects often terminated in ventricular tachycardia and ventricular fibrillation. Pretreatment with atropine sulfate, chlorisondamine chloride or propranolol HCl did not influence the occurrence of the arrhythmias although the latter compound did decrease the incidence of fatal ventricular fibrillation. The antiarrhythmic agents quinidine sulfate, procaine amide HCl, lidocaine HCl, and diphenylhydantoin sodium caused no significant effect on the ectopic beats produced by McN-2165, but they significantly decreased the occurrence of fatal ventricular fibrillation. The administration of McN-2165 may furnish a method for the detection of more effective ventricular antiarrhythmic agents.