Experimental Anti‐Arrhythmic Properties of Melperone, a Neuroleptic Butyrophenone

Abstract

The neuroleptic butyrophenone, melperone, has been compared with antiarrhythmics, neuroleptics, α‐blockers and β‐blockers in various experimental arrhythmias. Melperone 0.01–1 mg/kg intravenously antagonized ouabain‐induced arrhythmias in conscious rabbits to the same degree as propranolol 2 mg/kg and quinidine 10 mg/kg intravenously probably mainly via a CNS depressive effect. It was found to be considerably weaker than propranolol 2 mg/kg, when anaesthetized guinea pigs were used. Melperone 0.1–10 mg/kg was inactive against aconitine‐induced arrhythmias. Melperone 1–5 mg/kg antagonized adrenaline‐induced arrhythmias in halothane‐sensitized guinea pigs like phentolamine 1–5 mg/kg intravenously and was more potent than chlorpromazine, propranolol and quinidine. This study and an electrophysiological study suggest that melperone might be a type III anti‐arrhythmic drug, which at the same time depresses CNS and reduces afterload.

The Mode of Antiarrhythmic Action of Melperone

“…The cardiac effects of neuroleptics have attracted attention mainly because of side-effects o n the cardiovascular system. Recently, however, melperone (a butyrophenone neuroleptic) has been found t o have interesting antiarrhythmic effects (Petersen 1978;Platou et a/. 1979;Msgelvang et a/.…”

Anti‐arrhythmic Action of Melperone in the Dog Heart in Situ

“…1978a). The drug has been reported to antagonize adrenalineinduced arrhythmias in guinea-pigs (Petersen 1978) and to increase the threshold for electrically induced ventricular fibrillation in anaesthetized open chest dogs (Olsson et al 1978). The question therefore arises whether melperone also can convert cardiac arrhythmias into normal sinus rhythm.…”

Correlation between Melperone Plasma Concentrations and Changes in the Effective Refractory Period of the Right Atrium and Ventricle of the Dog

“…Melperone (a butyrophenone neuroleptic) possesses anti-arrhythmic activity in experimental animals (Olsson etal. 1978;Petersen 1978;Platou et al 1979) and in patients with acute myocardial infarction (Ovesen & Msgelvang, personal communication). The drug increases the action potential duration and the effective refractory period (ERP) of isolated heart muscle preparations (Arlock ef al.…”