We investigated the effects of a new antiulcer agent,
SWR-215 ([[(1,2-dihydro-2-oxo-4-quinolinyl)methyl]thio]-N-[[[4-(1-piperidinyl methyl)-2-pyridinyl]oxy]-Z-2-butenyl]
acetamide), on
histamine H2-receptors, gastric acid secretion and various acute experimental gastric lesions.
SWR-215 showed unsurmountable
histamine H2-antagonism on isolated guinea-pig atrium. In gastric secretion studies,
SWR-215 exhibited potent and durable inhibitory effects, and the antisecretory activities were much stronger than that of
roxatidine acetate hydrochloride (
roxatidine): 5 times stronger on basal
acid secretion in pylorus ligated rats, 11 times stronger on
histamine-stimulated
acid secretion in acute
fistula rats, and 2 times stronger on
histamine stimulated
acid secretion in Heidenhain-pouch dogs, respectively. In various experimental acute gastric lesion studies,
SWR-215 potentially inhibited almost all acute gastric and duodenal lesions compared with
roxatidine, especially
indomethacin-induced and HCl-
ethanol-induced gastric lesions, and the inhibitory effects were exhibited at the same or lower doses than those which caused the antisecretory effect. Furthermore, it was considered that the mucosal protective effect of
SWR-215 was probably unrelated to the endogenous
prostaglandin system in gastric mucosa. These results suggest that
SWR-215 possesses both durable antisecretory and mucosal protective effects, and is expected to be a useful
drug for the treatment of patients with
peptic ulcers.