[Gastrin/CCK-B receptor antagonists for a novel antiulcer agent].
Gastrin plays an important role in gastrointestinal functions such as gastric secretion and mucosal growth. The hypergastrinemia that results from long-term treatment with proton pump inhibitors and histamine H2-receptor antagonists induces hyperplasia of enterochromaffin-like (ECL) cells and increases the secretory response to pentagastrin (acid rebound). Recently, potent and selective gastrin/CCK-B-receptor antagonists, L-365,260, PD136450 and YM022, have been developed. These compounds inhibit basal and meal-stimulated acid secretion as well as pentagastrin-stimulated acid secretion in rats and dogs. Long-term treatment with gastrin/CCK-B-receptor antagonists does not cause hyperplasia of ECL cells and acid rebound at all. Moreover, they prevent hyperplasia and acid rebound induced by proton pump inhibitors and histamine H2-receptor antagonists. Therefore, gastrin/CCK-B-receptor antagonists are suggested to be novel antiulcer and antisecretory agents without potential for acid rebound, hyperplasia and carcinoid.
Miyata
K
K
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Japan.
Nishida
A
A
Honda
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology; D006965:Hyperplasia; D051381:Rats; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D000897:Anti-Ulcer Agents; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin