ABILITY OF PIMOZIDE TO PREVENT INHIBITION BY DOPAMINE ANALOGS OF CARDIOACCELERATOR NERVES IN CAT HEARTS

Abstract

The dopamine receptor blocking agent, pimozide, antagonized inhibitory actions of apomorphine, N,N-dimethyldopamine and 5,6-dihydroxy-2-dimethyl-aminotetralin (M-7) on stimulation-induced positive chronotropic responses of cat hearts in both in vivo and in vitro experiments. Pimozide did not antagonize the inhibitory effect of clonidine in in vitro experiments. Phentolamine, an .alpha.-adrenergic blocking agent, antagonized the inhibitory actions of dopamine analogs at 1.0 .mu.g/ml concentration in in vitro experiments. Phentolamine, 0.3 .mu.g/ml, only attenuated the response of N,N-dimethyldopamine but did not antagonize the effects of apomorphine and M-7. Lower concentration of phentolamine, 0.1 .mu.g/ml, showed marked inhibition to the inhibitory effect of clonidine. Both phentolamine and pimozide potentiated stimulation-induced positive chronotropic responses of cat right atria. Possibility of the presence of dopaminergic inhibitory system near the .alpha.-adrenergic inhibitory system in cardioaccelerator nerve terminal is discussed.