Dissimilarities between droperidol and phentolamine on vascular tone and dopamine and norepinephrine vasoconstriction

Droperidol has been found to have an alpha-adrenoceptor blocking potency comparable to phentolamine in in vitro studies where norepinephrine was used as the alpha agonist. Because dopamine also stimulates alpha receptors, its vasoconstrictor effects should be similarly inhibited by droperidol and phentolamine. Because the aforementioned comparisons have not been examined in vivo, we continuously infused either droperidol or phentolamine into a denervated canine hindlimb, perfused at a constant rate of blood flow, and measured changes in the basal perfusion pressure and its response to intra-arterial injections of dopamine and norepinephrine. It was found that 1) droperidol was much less potent than phentolamine in blocking the vasoconstrictor response to dopamine and norepinephrine. 2) Phentolamine's inhibition of dopamine was similar to its effect on norepinephrine whereas droperidol had the opposite effect, producing a greater inhibitory effect on norepinephrine than on dopamine. 3) The initial decrease in vascular resistance at the onset of steady state plasma levels of droperidol was quite transient while with phentolamine a corresponding decrease in vascular tone was more prolonged.