Actions of Metiamide, an H2-Histamine Receptor Antagonist, on Gastric H+ and Pepsin Secretion in Dogs

Metiamide, a thiourea analog of histamine, is an antagonist of the gastric histamine receptor (type H2). At doses of 0.2 and 0.5mg per kg-hr, it acted as a potent competitive inhibitor of H+ secreted in response to step-doses of histamine, pentagastrin, and Urecholine. At a dose of 2.5mg per kg-hr, metiamide almost completely inhibited histamine stimulation (acting uncompetitively), but had a less potent effect on pentagastrin and 2-deoxyglucose stimulated H+ secretion. By contrast, during metiamide administration, pepsin secretion stimulated by the cholinergic stimuli, Urecholine and 2-deoxyglucose, was further increased, while H+ secretion was inhibited. These data are difficult to explain on the basis of strict specificity of metiamide for the gastric H2-histamine receptor, and several possible postulates are discussed.