Antagonism of vasodepressor and gastric secretory responses to histamine by the H2-receptor antagonists, ranitidine and cimetidine, in the anaesthetized dog.

1 The new H2-receptor antagonist, ranitidine, has been compared with cimetidine as an inhibitor of gastric acid secretion in the anaesthetized dog. 2 Both ranitidine and cimetidine given intravenously inhibited histamine-induced gastric secretion in a dose-related manner. Ranitidine was 4.2 times more potent than cimetidine when given as an intravenous infusion and 9.6 times more potent as an intravenous bolus dose. 3 In a separate series of experiments, ranitidine was compared with cimetidine as an antagonist of vasodepressor responses to histamine. Mepyramine alone displaced the histamine dose-response curve to the right. After a maximally effective dose of mepyramine, further displacement could be achieved with ranitidine and cimetidine, ranitidine being 19.2 times more potent than cimetidine. 4 Ranitidine alone has no effect on vasodepressor response curves to histamine, acetylcholine or (-)-isoprenaline or on vasopressor response curves to phenylephrine. 5 These results indicate that displacement of the histamine dose-response curve after mepyramine blockade by ranitidine and cimetidine is due to selective H2-receptor antagonism.