Sadayoshi Onodera, Masato Tanaka, Misao Aoyama, Yoko Arai, Niro Inaba,
Takao Suzuki, Akiko Nishizawa, Masahiro Shibata and Yasuo Sekine
Pharmaceuticals Research Laboratories, Fujirebio Inc., 51 Komiya-cho,
Hachioji, Tokyo 192-0031, Japan
Abstract: Lafutidine is a new type antiulcer agent with antisecretory
and gastroprotective activities. We investigated the effect of lafutidine
on indomethacin-induced antral ulcer 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 microgram/kg, p.o. also
reduced the ulcer area. Chemical deafferentation of capsaicin-sensitive
neurons or NG-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.
Keywords: Lafutidine, Indomethacin, Non-steroidal antiinflammatory drugs-induced
ulcer,
Capsaicin-sensitive neuron, Histamine H2-receptor antagonist