Drugs Acting at the Gaba-Benzodiazepine Receptor Complex : Attenuate Ethanol-Induced Gastric Mucosal Damage In vitro

Benzodiazepines (BZs) were reported to protect against ethanol-induced gastric damage in rat's in vivo and in vitro model. However, the effects of some drugs in the new in vitro model do not agree with the results reported before in vivo studies. Therefore, the present study was designed to modify the new in vitro model and to assess the gastroprotective effects of some BZs, and also some new compounds. Gastric mucosal damage was induced by instillation of ethanol into the isolated rat stomach kept in aerated Kreb's solution at 37C in an organ bath. Drugs or their vehicles were administered inside the bath 15 min before ethanol. The results indicated that gastric mucosal damage was significantly reduced by clonazepam, as well as by Ro 15-4513 (partial BZR inverse agonists) pretreatment, significantly reversed by flumazenil (a central BZR antagonist). CGS 9896 (a partial agonist at the BZRs) and Ro 5-3663 (an atypical BZ, which bind to the picrotoxin site) did not offer any protection against ethanol. The results suggest a local, gastric mediation of ethanol effect and the gastric protective action of BZs through their action on a local, central-type BZRs located in rats stomach