Effects of ranitidine, a new histamine H2-receptor antagonist, on secretagogue-stimulated gastric secretion in Heidenhain pouch dogs (author's transl)

The effects of ranitidine on gastric secretion stimulated with gastric secretagogues were studied in 6 Heidenhain pouch dogs (both male beagle and mongrel). Cimetidine was used as a reference drug. Either histamine 2HCl (40 micrograms/kg), pentagastrin (2 micrograms/kg) or carbachol (2 micrograms/kg) was given intramuscularly, every 15 min for 120 min. Gastric juice was collected at each 15 min interval and analyzed for volume, acidity and pepsin activity. Either ranitidine (0.3, 1 or 10 mg/kg) or cimetidine (1 or 10 mg/kg), packed in a gelatin capsule, was given orally 60 min before the initial injection of each stimulant. Both ranitidine and cimetidine dose-dependently inhibited histamine- and pentagastrin-stimulated gastric secretion (volume, acid and pepsin output). These agents also inhibited the carbachol-stimulated secretion, but the antisecretory effects were weak as compared with their effects on histamine- and pentagastrin-stimulated secretions. The antisecretory effect of ranitidine on each stimulant is roughly 2 to 17 times more potent than cimetidine on the basis of ED50 (anti-secretory dose which inhibits gastric secretion by 50%). The antisecretory effect of ranitidine (10 mg/kg) on pentagastrin-stimulated secretion was observed even 10 hr after its oral administration.