MECHANISM OF EBROTIDINE PROTECTION AGAINST GASTRIC-MUCOSAL INJURY INDUCED BY ETHANOL

1. The gastroprotective properties of a new H-2-receptor antagonist, ebrotidine, against ethanol-induced mucosal injury was investigated. 2. Groups of rats, with and without indomethacin pretreatment, received intragastrically either a dose of ebrotidine or vehicle only, followed by ethanol given at various intervals up to 4 hr. The gastric mucosa, 30 min after the ethanol challenge, was then subjected to macroscopic and histologic examination, and physicochemical measurements. 3. Ebrotidine at doses of 50 mg and higher per kg body wt effectively prevented the alcohol-induced mucosal injury, even in the presence of indomethacin. The protective effect was demonstrable already at 30 min, reached maximum at 1 hr, and persisted up to 3 hr. 4. Physicochemical analyses established that ebrotidine elicited 30% increase in mucus gel dimension, caused 19-20% increase in glycolipids and phospholipids, and evoked 21% increase in sulfomucin and 18% in sialomucins. As a consequence, the mucus gel viscosity increased by 1.4-fold, H+ retardation capacity by 16%, and hydrophobicity by 65%. 5. The results demonstrate that ebrotidine is a unique H-2-antagonist endowed with a remarkable mucosal strengthening capability.