ISOPROTERENOL ANTAGONISM OF CARDIOSELECTIVE BETA-ADRENERGIC-RECEPTOR BLOCKING-AGENTS - COMPARATIVE-STUDY OF HUMAN AND GUINEA-PIG CARDIAC AND BRONCHIAL BETA-ADRENERGIC RECEPTORS
PA2 values against isoproterenol were determined for a number of cardioselective and noncardioselective .beta.-adrenergic receptor blocking agents using human and guinea-pig isolated atrial and bronchial or tracheal preparatiaons to study possible species differences. No significant differences in pA2 values for propranolol, pindolol, Ro 3-4787, acebutolol, atenolol, practolol, metoprolol, H 87/07 and tolamolol on bronchial or tracheal .beta.-adrenergic receptors of both species were found. With respect to atrial .beta.-adrenergic receptors, significantly lower pA2 values for human preparations, as compared to guinea-pig preparations, were found for tolamolol and CI 775 [1-([3,4-dimethoxyphenethyl]amino)-3-(m-tolyloxy)-2-propanol]. These are the only 2 agents in the series that derive their cardioselectivities from specific N substitutents. The different potencies of only these 2 compounds in antagonizing isoproterenol on atrial .beta.-adrenergic receptors of both species suggest a difference in an accessory receptor area close to the site that interacts with the N atom of .beta. adrenergic agents. [Drug side effects are discussed.].