Antisecretory and ulcer healing effects of S-0509, a novel CCK-B gastrin receptor antagonist, in rats

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.