PHARMACOLOGICAL PROFILES OF A NEW ANTIULCER AGENT, SWR-215

We investigated the effects of a new antiulcer agent, SWR-215 dihydro- 2-oxo-4-quinolinyl)methyl]thio]-N-[[[4-(1- ylmethyl)-2-pyridinyl]oxy]- Z-2-butenyl]acetamide), on histamine H-2-receptors, gastric acid secre tion and various acute experimental gastric lesions. SWR-215 showed un surmountable histamine H-2-antagonism on isolated guinea-pig atrium. I n gastric secretion studies, SWR-215 exhibited potent and durable inhi bitory effects, and the antisecretory activities were much stronger th an that of roxatidine acetate hydrochloride (roxatidine): 5 times stro nger on basal acid secretion in pylorus ligated rats, 11 times stronge r on histamine-stimulated acid secretion in acute fistula rats, and 2 times stronger on histamine stimulated acid secretion in Heidenhain-po uch dogs, respectively. In various experimental acute gastric lesion s tudies, SWR-215 potentially inhibited almost all acute gastric and duo denal lesions compared with roxatidine, especially indomethacin-induce d 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 effec ts, and is expected to be a useful drug for the treatment of patients with peptic ulcers.