Gastroprotective mechanism of lafutidine, a novel anti-ulcer drug with histamine H-2-receptor antagonistic activity

Lafutidine (CAS 118288-08-7, FRG-8813) is a novel histamine H-2-receptor an tagonist with gastroprotective activity The aim of this study was to invest igate the property of the gastroprotective activity of lafutidine by examin ing the effect on ammonia-induced change in transmucosal potential differen ce (PD), basal gastric mucosal blood flow (GMBF) and noxious agent-induced cell damage. Intragastrical application of lafutidine accelerated the recov ery of the PD reduction after exposure of the mucosa to 0.25 % ammonia solu tion and the accelerating effect was abolished by chemical deafferentation, but not with indometacin, a cyclooxygenase inhibitor. The application of c apsaicin, as a reference compound, significantly promoted the recovery of t he ammonia-induced PD reduction and this effect was not altered with indome tacin. Lafutidine given intragastrically caused a sustained increase in GMB F in a dose-dependent fashion, which was also completely inhibited in the d eafferentated rats. In vitro studies revealed that, in contrast to 16,16-di methyl prostaglandin E-2 lafutidine did not protect isolated gastric superf icial epithelial cells from ethanol- or ammonia-induced damage. In conclusi on, the gastroprotection of lafutidine is induced by promoting the restitut ion of the damaged mucosa after a noxious agent, not by directly protecting the epithelial cells and this effect may be caused through the mechanism o f capsaicin-sensitive afferent nerves.