A quantitative study of metiamide, a histamine H2-antagonist, on the isolated whole rat stomach.

Abstract

An isolated whole stomach preparation from immature rats is described. The lumen of the stomach was perfused and the H ion activity of the perfusate recorded continuously. The mean basal acid secretion before stimulation was 4.19 .+-. 0.31 .times. 10-8 mol min-1. Metiamide did not significantly reduce this spontaneous secretion. The preparation gave dose-dependent responses to histamine (10-5-10-4 M) which were readily reversed on washing. The effect of metiamide on histamine-stimulated acid secretion was investigated. Metiamide, at doses of 3 .times. 10-6 M, 10-5 M and 3 .times. 10-5 M, caused a parallel displacement of the histamine dose-response curve, indicating competitive antagonism. These dose-response curves were used to calculate dose ratios (DR) for metiamide. A plot of log10 (DR-1) against log10 [antagonist] gave a pA2 [scale for measuring drug antagonism, effective concentration of agonist to antagonist] value for metiamide of 5.91.