Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of
gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and
antimicrobial agents.
Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-
benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only
drug combining
acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The
drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect 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
ranitidine,
omeprazole and
lansoprazole.
Ebrotidine has also been demonstrated 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 A2 activities. Another important property of
ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori
lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the
lipopolysaccharide in mucosal
integrin receptor interaction with
proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of
mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that
ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of
gastrin release by
somatostatin. This activity of
ebrotidine apparently stems from the
drug's ability to counter the untoward effect of H. pylori on the binding of
somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of
acid suppressant, gastroprotective and anti-H. pylori activities makes
ebrotidine a
drug of choice in the treatment of
gastric disease caused by H. pylori.