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.
Al-Mulla Hummadi
Y M
YM
Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad 12114, Iraq.
Najim
R A
RA
Farjou
I B
IB
D000345:Affinity Labels / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001386:Azides / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D002998:Clonazepam / Q000494:pharmacology / Q000627:therapeutic use; D000431:Ethanol / Q000009:adverse effects*; D005442:Flumazenil / Q000494:pharmacology / Q000627:therapeutic use; D018757:GABA Modulators / Q000494:pharmacology / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
D000345:Affinity Labels; D001386:Azides; D002492:Central Nervous System Depressants; D018757:GABA Modulators; D001569:Benzodiazepines; D000431:Ethanol; D005442:Flumazenil; D002998:Clonazepam; C042957:Ro 15-4513