Pharmacological properties of the hydroxylated histamine, (±)-4(5)-(2-amino-1-hydroxyethyl)-imidazole

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Abstract
The pharmacological effects of the β-hydroxylated histamine, 4(5)-(2-amino-1-hydroxyethyl)-imidazole, on smooth muscle contraction of the ileum (H1-receptor activity) and gastric acid secretion (H2-receptor activity) of the guinea-pig were investigated and compared with those of histamine. Although β-hydroxy histamine contracted the ileum with the same maximal response as hstamine, the concentration response curve was shifted to the right by approximately three orders of magnitude. At submaximal concentrations, co-administration of β-hydroxy histamine with histamine revealed only additive effects. This H1-activity was competitively inhibited by diphenhydramine. Similarly, the hydroxylated analogue also increased intracellular cyclic AMP level and [14C] aminopyrine accumulation as a marker of acid secretion in the parietal cells. However, the EC50 was approximately ten fold that of histamine. This H2-receptor activity was inhibited completely by cimetidine. These results suggest that β-hydroxy histamine possesses nearly full intrinsic activities at both H1 and H2-receptors and that the introduction of a hydroxyl group at the β-carbon reduces and dissociates these activities.