[Effects of IGN-2098, a new histamine H2-receptor antagonist, on gastric secretion and gastric and duodenal lesions induced in rats. Comparison with roxatidine].

Abstract

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-, water-immersion 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 anti-lesion 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.

• Authors: S Okabe, M Narita, S Nakaji, Y Takinami, O Kawano, N Misaki
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 99 Issue 3 Pg. 167-80 (Mar 1992) ISSN: 0015-5691 [Print] Japan
• PMID: 1354631 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Ulcer Agents
• Histamine H2 Antagonists
• Piperidines
• Pyrimidinones
• IGN 2098
• roxatidine acetate

Topics

• Animals
• Anti-Ulcer Agents (administration & dosage, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Duodenal Ulcer (prevention & control)
• Gastric Juice (metabolism)
• Histamine H2 Antagonists (administration & dosage, pharmacology, therapeutic use)
• Male
• Piperidines (administration & dosage, pharmacology, therapeutic use)
• Pyrimidinones (pharmacology, therapeutic use)
• Rats
• Rats, Inbred Strains
• Stomach Ulcer (prevention & control)