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Abstract-Affinities of denopamine, a new cardiotonic agent, and several (3 adrenergic drugs for turkey erythrocyte membranes (TEM) and rat reticulocyte membranes (RRM) which contain homogeneous 31 and a2-receptors, respectively, were studied by receptor binding.The order of potencies of denopamine and several (3-adrenergic agonists in displacing 3H-dihydroalprenolol binding (K;, nM) in TEM was isoproterenol (Iso, 27)>norepinephrine (Nor, 360) >epinephrine (Epi, 860)>dobutamine (DB, 1380)>denopamine (1540)>dopamine (DA, 49500). The order in RRM was Iso (7.3)>Epi (58)>DB (750)>Nor (1090)>denopamine (2300)>DA (26800).In the presence of GTP, competition curves for full agonists like Iso, Epi and Nor shifted to the low affinity side (K; values increased by 300-500% in TEM and 200-460% in RRM), and the slopes were steepened in both membrane preparations.The K; value for denopamine increased only in TEM (70%) and that in RRM was not influenced by GTP. This suggests that denopamine has an agonist property at the 81-receptor but not at the 32-receptor and that the intrinsic activity at the e9 -receptor of the drug is lower than full agonists.Affinities of DB and DA for TEM were influenced by GTP as well as those for RRM, although the extent of the rightward shift was less than full agonists.

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A series of N-tetrazolylpyridinecarboxamides was prepared and evaluated for antiallergic activity by the passive cutaneous anaphylaxis (PCA) assay. From the structure-activity relationships (SAR) of this class of compounds, it was revealed that the N-tetrazolylcarbamoyl group as an acidic functionality is required to be at the 2-position of the pyridine nucleus and that the phenyl group as a subtituent is not necessarily required for activity. 6-Methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarboxamide (36) showed good oral activity and low toxicity.