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.
Najim
R A
RA
Department of Pharmacology, College of Medicine, University of Baghdad, Iraq.
Karim
K H
KH
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005442:Flumazenil / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects
D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D000431:Ethanol; D005442:Flumazenil; D002998:Clonazepam; C022193:Ro 5-3663; D007213:Indomethacin