EFFECT OF PROPRANOLOL ON THE BLOCKADE OF ALPHA ADRENERGIC RECEPTORS

¹ Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington

Previous studies from this laboratory have demonstrated the antagonism of various alpha blockers by the beta blocking agent, dichloroisoproterenol. In the present studies, the alpha responses of agents possessing both alpha and beta adrenergic properties (epinephrine and norepinephrine) were antagonized by phenoxybenzamine and exhibited partial recovery after subsequent administration of propranolol. However, the alpha responses of agents possessing only an alpha stimulatory property (methoxamine and oxymetazoline) were not restored upon subsequent administration of propranolol. It was also shown that, even after the antagonism of phenoxybenzamine by propranolol, the phenoxybenzamine-induced blockade reappeared after the effects of propranolol had dissipated. These data therefore demonstrate that only the agonist possessing both alpha and beta activities can undergo the reversal and recovery. It is postulated that this antagonism does not involve a displacement mechanism of phenoxybenzamine by propranolol but is associated with the unmasking of residual alpha receptor sites which were not blocked by the original dose of phenoxybenzamine.