The antisecretory profile of action of the H2-receptor antagonists, famotidine, loxtidine, ranitidine and L-643,441 on the rat isolated gastric mucosa

Four H2-receptor antagonists, famotidine, loxtidine, ranitidine and L-643,441 were tested against gastric secretory concentration-response curves to histamine, methacholine and dibutyryl cyclic AMP (dbcAMP) on the rat isolated gastric mucosa. All four drugs inhibited the secretory response to histamine, but the nature of this H2-receptor antagonism differed according to the drug. Ranitidine and famotidine were competitive, fully surmountable antagonists of histamine, but loxtidine and L-643,441 were unsurmountable antagonists. At high concentrations, the H2-receptor antagonists caused a small inhibition of the secretory response to methacholine but had no effect on the secretory response to dbcAMP. The rat isolated gastric mucosa is a useful preparation for characterisation of the antisecretory effects of H2-receptor antagonists.