Indecainide

Abstract: Clinical failure of antiarrhythmic drugs often occurs in practice. Therefore, there is a need for new, effective and long-acting drugs with a wide therapeutic range and a low level of toxicity. Most new class I compounds block the fast sodium ion inward current of myocardial cells. According to their effects on the recovery kinetics of the sodium ion channel, these drugs are classified into 3 groups: IA (intermediate--cibenzoline, pirmenol, hydroxy-3-S-dihydroquinidine, quinacainol); IB (fast--tocainide, moricizine); IC (slow--flecainide, encainide, propafenone, lorcainide, indecainide, recainam and penticainide). Class IC drugs greatly depress intracardiac conduction and are the most potent antiarrhythmic compounds able to suppress ventricular premature beats. However, it is doubtful that long-term suppression of ventricular arrhythmias will improve survival of the patients. Some new drugs have been developed belonging to other classes: class II, esmolol, a new ultrashort-acting beta blocker; class III, N-acetyl-procainamide and sotalol, which prolong duration of the action potential and increase ventricular refractoriness; class IV, the mixed sodium ion-calcium ion-potassium ion antagonist, bepridil. The pharmacologic properties and the clinical effects of these new antiarrhythmic drugs are reviewed. However, future therapeutic trends will depend on the results of large multicenter clinical secondary prevention trials such as the Cardiac Arrhythmia Suppression Trial. New antiarrhythmic drugs with original electrophysiologic profiles and minimal adverse effects must prove their ability not only to suppress arrhythmias but also to reduce sudden cardiac death rate.

Abstract: Intracellular potentials were recorded from rabbit atria, cardiac Purkinje cells and papillary muscles before and after exposure to various concentrations of indecainide. The effects of aprindine also were studied in the atrial preparations. Both drugs depressed the maximum rate of depolarization (MRD) in a dose-related manner, indecainide being approximately ten times more potent than aprindine. Aprindine caused a dose-related bradycardia, but indecainide had no significant effect on sinus node frequency. Indecainide had a dose-related negatively inotropic effect in normal, half-normal and twice-normal extracellular calcium concentrations. Indecainide shortened action potential duration (APD) in atrium and Purkinje cells but prolonged APD to 50% repolarization in ventricular muscle. The actions of indecainide were extremely persistent. No significant recovery of MRD was observed after pauses in stimulation of up to 16 s. Indecainide had no effect on effective refractory period (ERP) measured by interpolated premature stimuli. Indecainide is therefore categorized as a Class 1c antiarrhythmic agent. The effects of both aprindine and indecainide on MRD were increased in hypoxic atria. Conduction velocity in hypoxic atria exposed to indecainide was greater than in controls, however, suggesting the possibility of improved cell-to-cell coupling.

Abstract: SummaryThe intracellular electrophysiological properties of a new, orally effective antiarrhythmic agent, indecainide hydrochloride, were studied in isolated canine myocardial preparations stimulated at 1 Hz and superfused with Tyrode's solution. In Purkinje fibers, indecainide (10−6 and 3 x 10−6M)