Protection against ethanol-induced gastric damage by drugs acting at the GABA-benzodiazepine receptor complex.

The protective effects of drugs acting at the GABA-benzodiazepine receptor complex against ethanol-induced gastric damage in rats were investigated. Gastric lesions were induced by administration of 1 ml absolute ethanol orally to rats. Administration of clonazepam (0.625-2.5 mg/kg, IP), which binds with high affinity to the benzodiazepine binding site of the GABA-benzodiazepine receptor complex, or Ro 5-3663 (2.5 or 5 mg/kg), which binds to the piorotoxinin site of the receptor complex, protected against ethanol-induced gastric damage. The protective effect of clonazepam (1.25 mg/kg, IP) against ethanol-induced gastric damage was reversed, dose dependently, by the specific benzodiazepine antagonist, flumazenil (5-20 mg/kg, IP). This protective effect of clonazepam or Ro 5-3663 seems to be specific to ethanol-induced gastric damage, since neither drug protected against indomethacin-induced gastric damage. These results present for the first time evidence of the involvement of drugs acting at GABA-benzodiazepine receptors in protection against ethanol-induced gastric damage.