ANTI-HELICOBACTER PYLORI ACTIVITIES OF EBROTIDINE - A REVIEW OF BIOCHEMICAL AND ANIMAL EXPERIMENTAL STUDIES AND DATA

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successfu l therapy regimens require a combination of H-2 blockers with gastropr otective and antimicrobial agents. Ebrotidine ethyl]amino]methylene]-4 -bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective a nd anti-tr, pylori properties. The drug not only displays a potent ant i-H. pylori activity alone, but also exerts a strong potentiating effe ct on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ran itidine, omeprazole and lansoprazole. Ebrotidine has also been demonst rated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A(2 ) activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopoly saccharide on the integrity of gastric epithelium. This includes count ering the interference by the lipopolysaccharide in mucosal integrin r eceptor interaction with proteins of extracellular matrix and the reve rsal of H. pylori disruptive effect on the binding of mucin to its gas tric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylo ri in feedback inhibition of gastrin release by somatostatin. This act ivity of ebrotidine apparently stems from the drug's ability to counte r the untoward effect of H. pylori on the binding of somatostatin to i ts specific receptor on the gastric mucosal G-cells. The unique combin ation of acid suppressant, gastroprotective and anti-H. pylori activit ies makes ebrotidine a drug of choice in the treatment of gastric dise ase caused by H. pylori.