Gastroprotective properties of ebrotidine. A review.

Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is a new antiulcer drug which combines the properties of an H2-receptor antagonist with those of a cytoprotective agent. The cytoprotective properties of ebrotidine are not dependent upon endogenous prostaglandin generation, but stem from the ability of the drug to induce mucosal responses manifested in the enhanced physicochemical characteristics of mucus gel. These include the increase in mucus gel dimension, viscosity, hydrophobicity and hydrogen ion retardation capacity. Improvements in mucus gel protective qualities with ebrotidine are directly related to the ability of the drug to enhance the synthesis and secretion of sulfo- and sialomucins and phospholipids of gastric mucus and to promote mucin macromolecular assembly. An equally important property of ebrotidine in promotion of ulcer healing is its capability to enhance the gastric mucosal expression of integrin receptors for the interaction with proteins of the extracellular matrix such as laminin. Furthermore, the accelerated ulcer healing with ebrotidine is reflected in a marked increase in the mucosal expression of EGF and PDGF receptors. The drug has also been shown to modulate the processes associated with cell cycle progression during ulcer healing, and is known to protect the gastric epithelial integrity from calcium imbalance. Thus, ebrotidine, unlike other H2-blockers, has a unique ability to promote the event essential for mucosal repair and the maintenance of mucosal integrity. These features make ebrotidine a drug of great potential in the treatment of ulcer disease.