Chronic administration of H2-antagonists does not alter gastric secretory responses to histamine, or the antisecretory activity of sufotidine.

Gastric secretory responses to histamine were investigated in anaesthetized dogs following treatment with oral ranitidine at 5 mg/kg twice daily for 358 weeks, and in isolated gastric mucosae from mice receiving sufotidine 240-280 mg.kg/day for 15 months. In neither study were there any significant differences between the acid secretory dose-response curves to histamine in control and test animals. The antisecretory activity of oral sufotidine (1 mg/kg) against histamine-induced acid secretion in the Heidenhain pouch dog was unaltered by twice daily dosing with sufotidine for 14 days. These studies on the effects of H2-antagonists on histamine-stimulated acid secretion found no evidence for development of direct tolerance at the parietal H2-receptor level.