Abstract

In a series of substituted piperazines, phenyl methyl piperazine (A1390) was found to have potent adrenergic blocking activity in animals. It blocks and reverses the pressor effects of epinephrine. It blocks, but does not reverse, the pressor effects of nor-epinephrine, ephedrine, desoxyephedrine and hydroxyamphetamine, but does not block naphthyl-methyl-imidazoline.

A1390 blocks the pressor response to anoxia, tilting, and carotid sinus occlusion. It also blocks the nictitating membrane response to superior cervical nerve stimulation.

A1390 does not prevent epinephrine tachycardia nor reduce epinephrine toxicity in mice. It has little atropine-like action, and is only weakly antihistaminic. It does not have a direct vasodilator action in the perfused rabbit ear or heart. The local anesthetic potency of this compound is comparable to that of procaine. Its antihypertensive action in rats has a duration much longer than the adrenolytic activity. A small rise in threshold for vagal inhibition of the heart occurred only after large doses of A1390.

Acute and chronic toxicity data indicate that its therapeutic ratio is relatively favorable.

Examination of the properties of congeners did not reveal consistent or definitive structure-activity relationships.