1992 Volume 99 Issue 3 Pages 167-180
A new compound, IGN-2098 [5, 6-dimethyl-2-{4-<3-(1-piperidinomethyl)phenoxy>cis-butenylamino}-4(1H)-pyrimidone-2HCl], was found to be a potential histamine H2-receptor antagonist in the guinea pig atrium. IGN-2098, given p.o., significantly and persistently (for more than 12 hr) inhibited the basal gastric secretion in pylorus-ligated rats. The agent also significantly inhibited the basal gastric secretion when given by the s.c.-, i.d. or i.p.-route. Stimulated gastric secretion in fistula rats in response to histamine, carbachol or pentagastrin was also significantly inhibited with IGN-2098 given s.c. Pretreatment with IGN-2098 (p.o.) significantly protected the gastric mucosa against pylorus ligation-, waterimmersion stress-, histamine-, indomethacin-, HCl·aspirin-, and HCl ethanol-induced gastric lesions. In addition, the agent significantly protected the duodenal mucosa against mepirizole-induced ulcers. Based upon the ED50 values, the antisecretory effects on histamine, carbachol or pentagastrin-stimulated acid secretion were 6.0, 37.0 or 80 times more potent than roxatidine, respectively. As to the antilesion effects on HCl·aspirin-induced gastric lesions or mepirizole-induced duodenal ulcers, IGN-2098 was 8.1 or 14.8 times more potent than roxatidine, respectively. These results suggest that IGN-2098 will be a useful drug for the treatment of gastric and duodenal lesions in man.
