The effects of a novel CCK-B/
gastrin receptor antagonist,
S-0509, on gastric acid secretion and the healing of
acetic acid ulcers in rats were examined.
S-0509, orally administered 1, 6, and 12 hr prior to a 3-hr pylorus
ligation, significantly inhibited basal gastric acid secretion in both normal rats and rats with
gastric ulcers. The inhibition was nearly dose-related, persisted for more than 15 hr, and proved to be more potent in rats with
ulcers than in normal rats. In addition,
S-0509 markedly inhibited
pentagastrin- and
carbachol-stimulated
acid secretion in both normal rats and rats with
ulcers, but failed to inhibit
histamine-stimulated secretions. In chronic
gastric fistula rats,
S-0509 also significantly inhibited
pentagastrin- and
carbachol-stimulated gastric acid secretion in a dose-related manner, but had no effect on
histamine-stimulated secretion. These effects were largely similar to those observed with
famotidine, although
famotidine also inhibited
histamine-stimulated secretion. A two-week treatment with
S-0509 markedly enhanced the
spontaneous healing of
acetic acid ulcers and prevented the delay in
ulcer healing caused by
indomethacin. Gastric secretion was significantly inhibited and the plasma
gastrin level was increased in the animals studied. It is concluded that
S-0509 is a promising new antisecretory
drug for the treatment of
peptic ulcers.