Furan H2-antagonist ranitidine inhibits pentagastrin-stimulated gastric secretion stronger than cimetidine.

In each of 7 healthy volunteers, the new furan H2-antagonist ranitidine (0.125, 0.25, 0.5, and 1.0 mg . kg-1 . hr-1) or the imidazole derivative cimetidine or normal saline were intravenously infused in the midhour of a 3-hr pentagastrin period (1.5 micrograms . kg-1 . hr-1 i.v.). With increasing doses of ranitidine, gastric acid secretion dropped dose dependently: 62, 78, 89, and 94%, respectively (P < 0.05 for all doses). A cimetidine dose of 0.82 mg . kg-1 . hr-1 (2.8 mumol . kg-1 . hr-1), equivalent to the highest ranitidine dose, led to a similar reduction of acid output (54%) as an eightfold smaller ranitidine dose. Apparently in human gastric mucosa, recognition of H2-receptors is not exclusively determined by the imidazole ring. Strong inhibitory efficacy of ranitidine was also reflected by the low calculated mean ID50 of 54 micrograms (0.15 mumol) . kg-1 . hr-1 and the IC50 of 36 ng/ml (0.1 microM). Acid inhibition by ranitidine involved both reduction in volume and acidity. The lowering effect on pepsin output was less pronounced though significant. Secretion of free N-acetylneuraminic acid and N-acetylneuraminic acid bound to glycoproteins did not change after H2-blocker administration indicating an unimpaired mucus secretion. In these short-term experiments, there were no obvious side effects or alterations in routine laboratory parameters including serum gastrin and prolactin attributable to either drug.