[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.
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001919:Bradycardia / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors; D007022:Hypotension / Q000139:chemically induced; D007093:Imidazoles / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D010042:Ouabain; C016910:nizofenone; D004837:Epinephrine