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 gastri c acid secretion and the healing of acetic acid ulcers in rats were examine d. S-0509, orally administered 1, 6, and 12 hr prior to a 3-hr pylorus liga tion, significantly inhibited basal gastric acid secretion in both normal r ats and rats with gastric ulcers. The inhibition was nearly dose-related, p ersisted for more than 15 hr, and proved to be more potent in rats with ulc ers than in normal rats. In addition, S-0509 markedly inhibited pentagastri n- and carbachol-stimulated acid secretion in both normal rats and rats wit h ulcers, but failed to inhibit histamine-stimulated secretions. In chronic gastric fistula rats, S-0509 also significantly inhibited pentagastrin- an d carbachol-stimulated gastric acid secretion in a dose-related manner, but had no effect on histamine-stimulated secretion. These effects were largel y similar to those observed with famotidine, although famotidine also inhib ited histamine-stimulated secretion. A two-week treatment with S-0509 marke dly enhanced the spontaneous healing of acetic acid ulcers and prevented th e delay in ulcer healing caused by indomethacin. Gastric secretion was sign ificantly inhibited and the plasma gastrin level was increased in the anima ls studied. It is concluded that S-0509 is a promising new antisecretory dr ug for the treatment of peptic ulcers.