Comparison of the electrophysiological effects of two neuroleptics, melperone and thioridazine, on isolated rat atria.

The effects of the two neuroleptics, melperone (a butyrophenone) and thioridazine (a phenothiazine), were compared on the electrical and mechanical activity of isolated rat atria. Both electrically stimulated and spontaneously beating atria were used. Melperone was found to prolong the effective refractory period while the threshold for electrical stimulation i.e. the excitability, was almost unaffected. Thioridazine caused a similar prolongation of the effective refractory period, but also decreased the excitability significantly. In contrast to melperone, thioridazine had a negative inotropic effect. The spontaneous pacemaker activity was depressed and the sinus node recovery time increased to a greater extent after melperone than after thioridazine. The results taken together with other recent data support the hypothesis that melperone may be a type III anti-arrhythmic according to the classification of Vaughan Williams, in contrast to thioridazine which has a quinidine-like action (type I). The results also indicate that melperone in addition to prolonging the effective refractory period, may act as an anti-arrhythmic agent by depressing automaticity.