ANTISECRETORY AND ANTIULCER EFFECTS OF YM020, A NEW H-ATPASE INHIBITOR, IN RATS AND DOGS(,K+)

We examined the effects of YM020 [(3-methyl-2-butenyl)oxy]-imidazo[1,2 -a]pyridine), a novel H+,K+-ATPase inhibitor, on gastric acid secretio n and experimental gastroduodenal lesions in rats and dogs. Intraduode nal, subcutaneous and oral YM020 inhibited basal gastric acid secretio n in pylorus-ligated rats with ED(50) values of 9.1, 9.1 and 9.5 mg/kg , respectively. Oral pretreatment with YM020 5 hr before ligation stil l suppressed acid secretion, with a potency a little less than that of omeprazole. In anesthetized dogs, intravenous YM020 inhibited histami ne-, methacholine- and pentagastrin-induced gastric acid secretion wit h ED(50) values of 0.05, 0.01 and 0.08 mg/kg, respectively. In Heidenh ain pouch dogs, although oral YM020 (3 mg/kg) inhibited histamine-indu ced acid secretion, acid output returned to control levels faster than in dogs treated with omeprazole. Oral YM020 inhibited the formation o f water-immersion restraint stress-, indomethacin-, absolute ethanol-, 0.7 N hydrochloric acid- and cysteamine-induced gastric or duodenal l esions with ED(50) values of 2.9, 4.3, 2.0, 11.7 and 8.4 mg/kg, respec tively. Moreover, subcutaneous YM020 also suppressed the formation of ethanol- and HCl-induced gastric lesions. These results suggest that Y M020 has an antisecretory effect almost the same as or 2 to 3 times we aker than those of omeprazole and that its duration is not as long as that of omeprazole in rats and dogs. Furthermore, YM020 possesses a cy toprotective effect and the mechanism of YM020 may be different to tha t of omeprazole.