Benzodiazepines protect against ethanol-induced gastric mucosal damage in vitro

The protective effects of drugs acting at the benzodiazepine receptors against ethanol-induced gastric damage were investigated using a newly developed in vitro model of the ethanol-induced gastric damage. The rat stomachs were isolated from the whole animal and kept in Kreb's solution at 37 degrees C. Gastric damage was induced by administration of 1 mL of 50% V/V ethanol into the isolated rat stomach. Administration of the benzodiazepine agonist, clonazepam (25, 50, 100 microg), or the partial benzodiazepine inverse agonist Ro15-4513 (50 or 100 microg), significantly protected against ethanol-induced gastric damage when these agents were administered 15 min before ethanol. The protective effects of these drugs were blocked by the benzodiazepine receptor antagonist flumazenil (200-400 microg). Flumazenil alone was found to aggravate ethanol-induced gastric damage (200-400 microg). The results of this study give evidence for the involvement of central-type benzodiazepine receptors located in the stomach in the protective action of benzodiazepines against ethanol-induced gastric damage.