Differential actions on rabbit nodal, atrial, Purkinje cell and ventricular potentials of melperone, a bradycardic agent delaying repolarization: effects of hypoxia.

1 Melperone, a butyrophenone tranquillizer, caused bradycardia in vivo and in vitro. 2 Although Melperone had alpha-adrenoceptor antagonist activity in the pithed rat, it was not a beta-adrenoceptor antagonist, nor was it a cholinoceptor agonist. 3 The bradycardic action could be attributed almost entirely to a prolongation by Melperone of action potential duration (APD) in sinus node cells, with little effect on the slow diastolic depolarization. 4 APD was prolonged by Melperone in atrial and ventricular muscle, and most of all in the bundle of His, but only moderately in the terminal Purkinje cells. 5 In all cardiac tissues depolarized by fast inward current. Melperone caused a dose-related reduction in the maximum rate of depolarization and conduction velocity. On desheathed frog nerve Melperone had a local anaesthetic potency equal to that of procaine. 6 There was no negative inotropic effect in cardiac muscle, nor interference with A-V nodal conduction, from which it was inferred that Melperone did not restrict slow inward current. 7 Melperone did not reduce hypoxic shortening of APD relative to the initial value at the start of hypoxia, but because APD was already lengthened by Melperone in normoxic conditions, APD90 during hypoxia remained close to normal values. There was no protection against hypoxic depression of contractions. 8 It was concluded that Melperone had class 1 and class 3 antiarrythmic actions and merited trial as an antiarrhythmic drug.