Antiulcer effect of lafutidine on indomethacin-induced gastric antral ulcers in refed rats.
Lafutidine is a new type antiulcer agent with antisecretory and gastroprotective activities. We investigated the effect of lafutidine on indomethacin-induced antral ulcer in refed rats. Subcutaneous indomethacin injection resulted 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 immediately after the indomethacin injection. Capsaicin at 3 mg/kg, p.o. and 16,16-dimethyl prostaglandin E2 at 3 microg/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 preventive effect of lafutidine and capsaicin. After the induction of gastric ulcer, 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 compared with that of the control group. In chemically-deafferentated rats, lafutidine 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-induced antral ulcer. These results may suggest that lafutidine, unlike cimetidine and famotidine, can prevent the indomethacin-induced antral ulcer formation and accelerate the healing of the ulcer in refed rats through mechanisms involving the capsaicin-sensitive afferent neurons and nitric oxide.
Onodera
S
S
Pharmaceuticals Research Laboratories, Fujirebio Inc., Hachioji, Tokyo, Japan.
Tanaka
M
M
Aoyama
M
M
Arai
Y
Y
Inaba
N
N
Suzuki
T
T
Nishizawa
A
A
Shibata
M
M
Sekine
Y
Y
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D005502:Food; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000187:drug effects* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D014945:Wound Healing
D000081:Acetamides; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D010880:Piperidines; D011725:Pyridines; D019335:Nitroarginine; C076948:lafutidine; D015738:Famotidine; D002927:Cimetidine; D015064:16,16-Dimethylprostaglandin E2; D002211:Capsaicin; D007213:Indomethacin