The new H₂-receptor antagonist mifentidine (DA 4577) was tested for its antisecretory and gastric motor effects in comparison with cimetidine and ranitidine. The Shay rat preparation (5 h) was used for studying gastric secretion; the gastric emptying of a liquid meal was chosen for studying gastric motility. All the three compounds inhibited acid secretion in a dose-dependent fashion. Calculated ED_50s were 2.3, 12.2 and 92.8 mg·kg^-1 for mifentidine, ranitidine and cimetidine, respectively. Therefore, in this animal model, mifentidine was about 40 times more potent than cimetidine and 5 times more potent than ranitidine. As far as gastric emptying is concerned, the effect of equiactive antisecretory doses (i.e. the respective ED_50s calculated from the previously established dose-response curves) of all the three antagonists was completely different. Cimetidine delayed emptying rate, whereas ranitidine accelerated it and mifentidine was completely ineffective. However, at higher doses, also this compound affected emptying rate by reducing it dose-dependently. Gastric and duodenal ulcers were induced in the rat by dimaprit (100 mg·kg^-1 intravenously) and cysteamine (250 mg· kg^-1 subcutaneously), respectively. As far as gastric ulcer is concerned, the ED_50s (the effective dose which protected 50% of the animals from lesions) were 0.23, 4.40 and 9.70 mg·kg^-1 for mifentidine, ranitidine and cimetidine, respectively. As regards duodenal ulcer, the ED₅₀ was 4.48 for mifentidine and 150.00 mg·kg^-1 for ranitidine. In this animal model, the efficacy of cimetidine was very low. Therefore an ED₅₀ could not be determined. In conclusion, results of the present investigation demonstrated that mifentidine is a potent antisecretory compound and an effective anti-ulcer agent in the rat.

1 The effects of the new H2-receptor antagonist famotidine, administered orally, on gastric secretion and emptying as well as on experimentally-induced gastric and duodenal ulcers were studied in the rat. Ranitidine was used as a reference compound.2 Both compounds inhibited acid secretion in a dose-dependent manner. Calculated ED_, values were 0.80 and 6.84mg kg' for famotidine and ranitidine, respectively. However, the duration of the antisecretory action was the same for both drugs. 3 The effect of the two drugs, administered at equiactive antisecretory doses, on gastric emptying was different. Ranitidine significantly accelerated the emptying rate whereas famotidine had no effect. 4 Famotidine reduced, in a dose-dependent manner, ulcer incidence in stomachs of dimaprit-treated rats and in duodena of cysteamine-treated animals with a potency respectively 2 and 7 times higher than that of ranitidine. 5 Famotidine is therefore an effective antisecretory and untiulcer'compound. Its potency, but not its efficacy, is higher than that of ranitidine. Moreover, the duration of the antisecretory action is virtually the same for both drugs.

The effects of adenosine and its metabolically stable derivative L-phenylisopropyladenosine (L-PIA), acting mainly on A₁ receptors, on gastric acid secretion were studied in the rat. Although inactive by intraduodenal route, subcutaneous adenosine significantly inhibited acid secretion. This inhibition, however, was not dose-dependent. On the contrary, L-PIA was able to decrease dose-dependently acid output by both subcutaneous and intraduodenal route, its ED₅₀ being 0.11 mg/kg subcutaneously and 0.24 mg/kg intraduodenally. The inhibitory effect of L-PIA was reduced by prior administration of theophylline. These results suggest that activation of A₁-receptors inhibits acid secretion in the rat.

Scarpignato, C., R. Tramacere, and A. Peuetta: Effect of famotidine and ranitidine on gastric secretion and emptying in the rat. Drug Dev. Res. 11:37-43, 1987.The antisecretory and gastric motor effects of the new H2-receptor antagonist famotidine (MK-208) were compared with those of ranitidine in the rat. The Shay rat preparation (5 hr) was used for studying gastric secretion. Gastric motility was assessed by measuring gastric emptying of a liquid meal. Both compounds inhibited acid secretion in a dosedependent fashion. Calculated EDs0 values were 0.80 and 6.84 mgakg-' for famotidine and ranitidine, respectively. Therefore, in this animal model, famotidine was about 9 times more potent than ranitidine. The duration of antisecretory action however, was virtually the same for both drugs. The effect of the two drugs -administered at equiactive antisecretory doses -on gastric emptying was different. Indeed, ranitidine significantly accelerated emptying rate, whereas famotidine was ineffective. The results of the present investigation demonstrate that famotidine is a potent and selective antisecretory compound.