Effects of AH-1058, a new antiarrhythmic drug, on experimental arrhythmiasand cardiac membrane currents

AH-1058 is a newly synthesized antiarrhythmic agent. We investigated the an tiarrhythmic and electrophysiological effects of AH-1058 in experimental ar rhythmia models and isolated cardiomyocytes. In the ouabain-induced arrhyth mia model of the guinea pig, pretreatment with AH-1058 (0.1-0.3 mg/kg, i.v. ) delayed the appearance of premature ventricular complex (PVC) and ventric ular fibrillation (VF) induced by intravenous infusion of ouabain. However, disopyramide (10 mg/kg, i.v.) delayed only that of PVC, and verapamil (1 m g/kg, i.v.) failed to affect the ouabain-induced ventricular arrhythmias. I n the reperfusion-induced arrhythmia model of the rat, in which 5-min coron ary occlusion and 10-min reperfusion were produced, AH-1058 (0.1-0.3 mg/kg, i.v.) inhibited the incidence of both ventricular tachycardia (VT) and VF, whereas disopyramide (5 mg/kg, i.v.) inhibited only reperfusion-induced VE On the other hand, a higher dose of AH-1058 (1 mg/kg, i.v.) did not affect the aconitine-induced arrhythmias in rats, which were inhibited by disopyr amide (5 mg/kg, i.v.). We also confirmed oral activity of AH-1058 in the re perfusion-induced arrhythmia model of the rat. AH-1058, at doses of 2-4 mg/ kg, dose-dependently inhibited VT and VE Electrophysiological experiments w ith patch clamp techniques revealed that AH-1058 potently suppressed the L- type Ca2+ currents in isolated cardiomyocytes of the guinea pig. These resu lts suggest that AH-1058 is a potent antiarrhythmic drug having a Ca2+ chan nel-blocking action. The antiarrhythmic profile of AH-1058 is different fro m that of disopyramide and verapamil.