Melperone: electrophysiologic and antiarrhythmic activity in humans

Previous studies in animals and in humans have shown that melperone, a neuroleptic butyrophenone, has class III electrophysiologic activity. However, its antiarrhythmic activity has not been assessed in humans. Accordingly, the electrophysiologic and antiarrhythmic effects of melperone were assessed in 23 patients with symptomatic ventricular tachyarrhythmias. Seventeen patients had electrophysiologic testing while receiving melperone. At oral daily dosages greater than or equal to 240 mg, melperone produced significant prolongations of QT intervals (385 +/- 11 vs. 355 +/- 22 ms, p less than 0.05), ventricular effective refractory periods (263 +/- 18 vs. 243 +/- 28 ms, p less than 0.05; 260 +/- 18 vs. 235 +/- 27 ms, p less than 0.01; and 243 +/- 23 vs. 222 +/- 28 ms, p less than 0.01; at 600-, 500-, and 400-ms pacing cycle lengths, respectively) and ventricular tachycardia (VT) cycle lengths (286 +/- 46 vs. 239 +/- 70 ms, p less than 0.05). Inducible VT was suppressed entirely in one patient. In three other patients, inducible sustained VT became nonsustained. No significant negative inotropic effects were observed. The majority of patients (70%) experienced some adverse effect, the commonest of which was neurologic. In conclusion, melperone had significant class III electrophysiologic and antiarrhythmic activity in humans. Its clinical use may be limited by the high incidence of adverse effects.