Studies on Mode of Antagonism between Adrenergic β-Mimetics and β-Blocking Agents (I). β-Blocking Action of Mescaline and its Derivatives

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Abstract
In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 [scale for the measurement of drug antagonism, effective concentration of agonist to antagonist] 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 and structure-activity 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 PR were almost 1, 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. The possibility that TMQ and ISO would interact with the same receptor sites is suggested. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed.