CARDIOVASCULAR EFFECT OF A NEW ANTIARRHYTHMIC DRUG——CHANGROLIN

Changrolin is 4-3', 5'-bis (N-pyrrolidinyl) methyl-4'-hydroxyanilino-quinazoline. It was found in our Institute to be a new antiarrhythmic drug. In anesthetized dogs, intravenous injection of 30 mg/kg (2mg/kg/min) did not cause a significant reduction of the total peripheral resistance, but the blood pressure, left ventricular systolic pressure and cardiac output were lowered significantly, The work of the left ventricle was weakened. A widening of the QRS complex and a prolongation of the P-R and Q-Tc intervals on EKG were observed. After cessation of the medication these indices tended to restore. Ghangrolin exhibited a cardio-vagal blocking effect but showed no adrenergic blocking action. Ouabain induced ventricular tachycardia in anesthetized dogs could be reverted to supra-ventricular or sinus rhythm, by intravenous drip of changrolin 4 mg/min for 120 minutes. This reversion occurred when the dose reached 4.5±2.1 mg/kg (±SD) while the concentration of changrolin in plasma was about 0.61±0.29 μg/ml. The concentration of changrolin in plasma rose to 0.89±0.23 μg/ml at 15 minutes and to 2.19±0.16 μg/ml at 120 minutes.The cardiovascular actions of changrolin were thus similar to that of quinidine.