Effects of
KB-5492, a new anti-
ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of
teprenone and
cimetidine.
KB-5492 administered orally at 12.5-200 mg/kg inhibited water-immersion stress- and
indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicating that
KB-5492 was more potent than
teprenone but less potent than
cimetidine.
KB-5492, administered orally at 12.5-100 mg/kg, also inhibited
ethanol-induced gastric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so
KB-5492 was 3 times more potent than
teprenone, whereas
cimetidine produced no obvious inhibition. In addition,
KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of
acetic acid-induced
gastric ulcers more potently than
teprenone and
cimetidine.
KB-5492 at anti-
ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal
hexosamine content induced by
aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that
KB-5492 has potent and broad anti-
ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.