[Effects of nizofenone on experimental arrhythmia in dogs]

The effects of nizofenone, a new compound with cerebral protective properties, were compared with those of quinidine on various types of experimental arrhythmia in dogs. Pretreatment with nizofenone (3 and 10 mg/kg, i.v.) markedly increased the amount of ouabain needed to cause cardiac toxicity in pentobarbital-anesthetized dogs, to the same degree as quinidine (10 mg/kg, i.v.). Nizofenone (1, 3 and 10 mg/kg, i.v.) was effective in reversing established ouabain-induced ventricular tachycardia in pentobarbital-anesthetized dogs. In contrast quinidine (3 and 10 mg/kg, i.v.) showed only weak activity in this test. Nizofenone (3 and 10 mg/kg, i.v.) significantly reduced the ectopic ventricular rate in pentobarbital-anesthetized dogs 24 hr after a two-stage ligation of the anterior descending coronary artery. Quinidine (10 mg/kg, i.v.), however, was more potent in this test. In addition, nizofenone, like quinidine, caused hypotension and bradycardia and prolonged the electrocardiogram QTc interval. On the other hand, nizofenone (1 and 10 mg/kg, i.v.) was inactive against epinephrine-induced arrhythmias in halothane-anesthetized dogs. Quinidine (10 mg/kg, i.v.) was effective in this test and also antagonized the pressor response induced by epinephrine. The effects of quinidine on adrenergically-induced arrhythmias are considered to be mediated through a blocking of the adrenergic alpha-receptors. Nizofenone did not show the adrenergic alpha-receptor blocking effect. Accordingly, the above findings suggest that the antiarrhythmic action of nizofenone may result from depressant effects on the cardiovascular system and from a membrane-stabilizing effect.