CONCERNING THE MECHANISMS OF THE CARDIOVASCULAR ACTIONS OF HEXAHYDRO-1-AZEPINEPROPIONAMIDOXIME (SU-4029)

¹ Research Department, CIBA Pharmaceutical Products Inc., Summit, New Jersey

The blockade of norepinephrine produced by the "reversible" adrenergic blocking agent phentolamine is negated by Su-4029. The blockade of norepinephrine produced by the "irreversible" blocking agent Dibenamine is not negated by Su-4029. Since phentolamine and Dibenamine are generally considered to function at the same locus in the adrenergic receptor substance these facts indicate that Su-4029 may have an action in the substance of the alpha receptors and that it may be at the same site as that affected by Dibenamine and phentolamine. The responses to a series of pressor phenylalkylamines following Su-4029 pretreatment fall into 3 categories: 1) irreversibly blocked are the amines with no or only p-hydroxylation; 2) reversibly blocked are the amines with hydroxylation on the carbon adjacent to the ring, i.e., the beta carbon; and 3) not blocked or augmented are the amines with m and p-hydroxylation or m or p plus beta-hydroxylation. It is suggested that part of the action, at least, of Su-4029 is to "deform" that portion of the alpha receptor substance which is affected by adrenergic blocking agents such as phentolamine and Dibenamine.