The chemistry of prostanoids and CCK2 antagonists

Abstract

The involvement of more neurotrasmiters, hormones and autocoids in the control of gastric acid secretion has resulted in a number of therapeutic approches directed toward achieving its inhibition. Although significant progress in obtaining CCK2 gastrin receptor antagonists as vell as EP3 receptor agonists has been made in recent years, compounds from either of these groups seem unlikely to dislodge the irreversibile proton-pump inhibitors and histamine H2-angonists as the preferred treatment in acid-related disoreders at present. All of the potencially antiulcerative useful prostanoids are in general synthetically produced closely related analogs of natural prostaglandins PGE1 and PGE2. For example, it was hoped that EP3 receptor agonists such as misoprostol and newly sinthetised, selectivelly and more active GR63799X, might prove beneficial as cytoprotective agents.

Učešće brojnih endokrinih hormona i neurotransmitera u kontroli gastrične sekrecije pruža mogućnost različitih terapijskih pristupa u tretiranju ulkusne bolesti i stanja hipersekrecije. Inhibitori protonske pumpe, H2 antagonisti histamina i muskarinskih receptora su veoma efikasni i bezbedni antiulkusni i antihipersekretorni lekovi. Iz ove grupe lekova u kliničkoj fazi ispitivanja su novi, reverzibilni inhibitori protonske pumpe i antagonisti H2 receptora druge generacije. U kliničkoj fazi ispitivanja nalaze se i brojni antagonisti CCK2-receptora kao potencijalni inhibitori gastrične sekrecije. Pored inhibicije gastrične sekrecije ovi potencijalni lekovi imaju i antianksiozni efekat. Citoprotektivna zaštita prostanoida, agonsta EP3 receptora za per os primenu je noviji pristup naročito u hroničnoj terapiji nesteroidnim antireumaticima koji mogu biti uzročnici ozbiljnih neželjenih efektata kao što su hipersekrecija gastritis, ulkus i gastrične hemoragije.