Antiulcer effect of lafutidine on indomethacin-induced gastric antral ulcers in refed rats

Lafutidine is a new type antiulcer agent with antisecretory and gastroprote ctive activities. We investigated the effect of lafutidine on indomethacin- induced antral ulcer in refed rats. Subcutaneous indomethacin injection res ulted in the formation of gastric antral ulcer. Lafutidine (1-10 mg/kg, p.o .) reduced the area of ulcer in a dose-dependent manner when administered i mmediately after the indomethacin injection. Capsaicin at 3 mg/kg, p.o. and 16,16-dimethyl prostaglandin Ea at 3 mu g/kg, p.o. also reduced the ulcer area. Chemical deafferentation of capsaicin-sensitive neurons or N-G-nitro- L-arginine treatment aggravated the ulcer formation and abolished the preve ntive effect of lafutidine and capsaicin. After the induction of gastric ul cer, lafutidine given twice daily for 2.5 days reduced the area of ulcer in a dose-dependent manner with a significant effect at 10 mg/kg, p.o., as co mpared with that of the control group. In chemically-deafferentated rats, l afutidine did not show any healing effect. Cimetidine (30 mg/kg, p.o.) and famotidine (1 mg/kg, p.o.) had no significant effect on indomethacin-induce d antral ulcer. These results may suggest that lafutidine, unlike cimetidin e and famotidine, can prevent the indomethacin-induced antral ulcer formati on and accelerate the healing of the ulcer in refed rats through mechanisms involving the capsaicin-sensitive afferent neurons and nitric oxide.