CCK2 receptor antagonists

Recognition that the gastrointestinal polypeptide hormone gastrin affects diverse actions, such as gastric acid secretion and gastrointestinal cell growth in peripheral tissues, has prompted efforts to obtain agents that inhibit its action. This has mainly been approached through the use of CCK2 receptor antagonists which also have the potential to inhibit cholecystokinin-mediated CNS effects, such as anxiety and pain. However, results obtained so far from compounds of this type in the clinic have been disappointing due to their low oral bioavailability. This has resulted from physicochemical limitations of the compounds examined, such as solubility, and attempts to further optimise these initial candidates have also spawned CCK2 receptor antagonists based on other structural types. These new compounds may ultimately demonstrate therapeutic utility for CCK2 receptor antagonists.