MECHANISM OF THE VASODILATOR RESPONSE TO PHENIPRAZINE

¹ Department of Pharmacology, Marquette University, School of Medicine, Milwaukee, Wisconsin

Pheniprazine (-phenylisopropylhydrazine, JB 516), an inhibitor of monoamine oxidase, when given i.v. to anesthetized dogs, produced a biphasic arterial blood pressure response, consisting of an immediate transient depressor response followed by a sustained pressor effect. The mechanism of the depressor response to pheniprazine was investigated utilizing intact dogs and also the perfused foreleg in dogs in which the pressor response was blocked. Vasodilatation to i.v. pheniprazine occurred in the perfused foreleg and was not diminished by acute denervation, thus eliminating a neurogenic mechanism. Other possibilities were studied in the denervated foreleg by comparing responses to histamine, acetylcholine or isoproterenol with those to pheniprazine before and after specific antagonists, viz., diphenhydramine, atropine and pronethalol, respectively. Only pronethalol reduced the response to pheniprazine; however, the degree of blockade of pheniprazine was much less than that of isoproterenol. Depletion of catecholamines and serotonin by reserpine pretreatment did not alter the depressor response to pheniprazine. It is concluded that the hypotensive response to pheniprazine does not resemble that caused by histamine or acetylcholine and is not altered by reserpine pretreatment. It appears to be partly due to the stimulation of beta-adrenergic receptors.