Studies on mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (I). Beta-blocking action of...

In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 values of propranolol (PR) and certain trimethoxybenzene derivatives were measured, using isolated guinea pig tracheal chains. Each of PR, mescaline (MES) and its derivatives gave almost the same pA2 values for TMQ and ISO. Introduction of an alkyl group into the N atom of MES increased the affinity to the receptor in the order of methyl and isopropyl as well as the structureactivity relationship of catecholamines, while that of hydroxyl group in the beta-position of the side chain decreased pA2 values. The slopes of the regression lines for anti-TMQ action of MES derivatives as well as PR were almost one, but those for their anti-ISO action were less than 0.3. 3,4,5-Trimethoxyaniline and 3,4,5-trimethoxybenzoic acid had little activity as beta-blocking agents. These results suggest the possibility that TMQ and ISO would interact with the same receptor sites. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed.