Abstract
The antiarrhythmic and direct cardiovascular effects of the new antiarrhythmic agent KW-3407, 5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11- dihydro[1]benzoxepino[3,4-b]pyridine 1.5 fumarate, were examined. To evaluate antiarrhythmic effects, two-stage coronary ligation-, digitalis- and adrenaline-induced spontaneously occurring arrhythmias were used. KW-3407, 20 mg/kg/10 min, suppressed these three arrhythmia models, similar to flecainide, mexiletine and phenytoin. The antiarrhythmic plasma concentrations, IC50, of KW-3407 for 24-hr and 48-hr coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 18.1, 14.4, 18.3 and 21.4 micrograms/ml, respectively; and these values were similar to one another. In the canine blood perfused atrioventricular (AV) node, sinoatrial node and papillary muscle preparations, KW-3407 decreased the sinoatrial rate and contractile force, and increased the coronary blood flow and AV conduction times, but these effects were weaker than those of disopyramide and flecainide and were short-lived. These results indicate that KW-3407 can be expected to become a clinically useful antiarrhythmic drug.
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