Effect of the new H2-receptor antagonist mifentidine on gastric acid secretion in the cat: comparison with cimetidine and ranitidine

Abstract

The effect of the H2-receptor antagonist mifentidine (DA 4577) was studied in conscious fistula cats in comparison with cimetidine and ranitidine. Two series of experiments were carried out. In the first, submaximal gastric secretion was induced by continuous intravenous infusion of dimaprit (a selective H2-agonist). Once a plateau of gastric secretion had been reached, antagonists were infused intravenously at increasing doses for 3 hr. Mifentidine, ranitidine, cimetidine or saline were administered in different days at random order. In the second set of experiments, equiactive doses (that is the respective ED50s calculated from the previously established dose-response curves) of all the compounds were infused during dimaprit-induced acid hypersecretion, in order to evaluate their duration of action. All the compounds inhibited acid secretion in a dose-dependent fashion. Calculated ED50s were 0.39 +/- 0.05, 0.49 +/- 0.04 and 10.13 +/- 0.33 mumol.kg-1.hr-1 for mifentidine, ranitidine and cimetidine respectively. After the infusion of the equiactives doses, the half-life (that is the time taken to return to 50% inhibition) was 76.4 +/- 14.7 min for mifentidine, 38.3 +/- 10.1 min for ranitidine and 33.6 +/- 2.9 min for cimetidine. These data demonstrate that mifentidine is a potent antisecretory compound with a duration of action longer than that of cimetidine and ranitidine.