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

The pharmacological effects of the beta-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 beta-hydroxy histamine contracted the ileum with the same maximal response as histamine, the concentration response curve was shifted to the right by approximately three orders of magnitude. At submaximal concentrations, co-administration of beta-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 beta-hydroxy histamine possesses nearly full intrinsic activities at both H1 and H2-receptors and that the introduction of a hydroxyl group at the beta-carbon reduces and dissociates these activities.