Effects of
FRG-8701, a new
histamine H2-receptor antagonist, on gastric acid secretion, necrotizing agents-induced gastric lesions and acute gastric or
duodenal ulcer in rats were studied. In lumen-perfused rats,
intravenous injection of
FRG-8701 reduced gastric acid secretion, and its antisecretory effect was almost equipotent to that of
famotidine but the duration of action was substantially longer. In pylorus-ligated rats, the antisecretory effect of intraduodenal
FRG-8701 administration was about 7 times more potent than that of
cimetidine.
FRG-8701 effectively inhibited macroscopic gastric hemorrhagic lesions induced by various kinds of necrotizing agents.
Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ED50 values for these lesions ranged from 1.1 to 9.4 mg/kg. On the other hand,
famotidine failed to reduce these lesions, and the cytoprotective effect of
cimetidine was observed only in high doses compared with the doses for antisecretory activity. In addition, the cytoprotective effect of
FRG-8701 was not affected by the treatment of
indomethacin or
N-ethylmaleimide.
FRG-8701 showed antiulcer activity against stress and
indomethacin gastric ulcer and
mepirizole duodenal ulcer. Its antiulcer effect was 5-15 times more potent than that of
cimetidine. These results indicate that
FRG-8701 is a new antiulcer
drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.