Search

41 patients with stable, frequent, chronic premature ventricular contractions have been treated with aprindine, and its therapeutic effectiveness evaluated by continuous electrocardiographic recording on tape. Excellent results (total suppression of the dysrhythmia) were obtained in 29 patients (71%), in whom the minimal effective plasma level ranged from 0.73 to 2.55 µg/ml (mean 1.35 µg/ml). Neurological side effects developed in 9 patients (22%), with plasma levels from 1.19 to 4.13 µg/ml (mean 2.65 µg/ml). The value of plasma level determinations is discussed.

The electrophysiological effects of aprindine, a new anti-arrhythmic drug, were investigated in isolated cardiac tissues of different animals. Diastolic depolarization and spontaneous firing were attenuated or abolished by aprindine. The action potential duration and effective refractory period were markedly shortened in Purkinje fibres. At the same concentrations, the action potential duration in atrial and ventricular muscle was not significantly altered. Membrane responsiveness curve was shifted to a more negative membrane potential. At concentrations above 5 mg/l, Purkinje fibres became inexcitable. Uptake and release of 14C-aprindine was studied in isolated heart preparations. Equilibration was not reached after an incubation period of 60 min and a final concentration of 10 times the concentration in the uptake fluid was attained after 60 min. The long-lasting effects on transmembrane potentials could be explained by the slow release of 14C-aprindine. A large fraction of the 14C-aprindine content was released with a time constant of 3 hr. The mechanism responsible for the in vivo anti-arrhythmic action and side effects are discussed.

Publisher Summary This chapter describes the various aspects of antiarrhythmic and antianginal agents. Cardiac arrhythmias generally result from enhanced automaticity or disturbances in conduction. These disturbances cause alterations in cardiac rate, regularity, origin of cardiac impulse, or sequence of activation of the atria and ventricles. A series of N -substituted-2-amino-l-(thienyl)ethanols were evaluated as β-blockers and was found to be less potent than propranolol as inhibitors of the tachycardic response to isoproterenol. A series of heterocyclic propanolamines had β-blocking activity, the most potent having ten times the activity of propranolol on the guinea pig atrial strip. UM-272, the dimethyl derivative of propranolol, exhibits neither the 6-blocking properties nor the local anesthetic properties of propranolol. UM-272 is effective against digitalis and myocardial infarction arrhythmias in the dog. In addition, UM-272 was shown to significantly increase ventricular fibrillation threshold and reduce the occurrence of ventricular fibrillation following acute occlusion of the left anterior descending coronary artery and its subsequent de-occlusion. Aprindine is a long-acting, orally effective antiarrhythmic agent that compares favorably with intravenous lidocaine in preventing ventricular arrhythmias after acute myocardial infarction.

1 A cross-over study with aprindine (100 mg daily after a loading dose of 200 mg), procainamide (4 × 1000 mg daily) and quinidine bisulphate (2 × 750 mg daily), all given orally, was performed in seventeen patients with stable chronic premature ventricular contractions following healed myocardial infarction. 2 The effectiveness of the treatment was evaluated during three consecutive weeks by continuous ambulatory tape recording of the electrocardiogram and repeated determinations of plasma levels were done. 3 The results showed that aprindine was more effective than procainamide and quinidine. 4 For the three drugs the therapeutic plasma levels varied markedly from patient to patient, but for each patient taken individually, the therapeutic activity could be correlated with the plasma levels.