Drugs acting at central benzodiazepine receptors attenuate ethanol-induced gastric lesions in rats.
The characteristics of the receptors involved in the protective action of benzodiazepines against ethanol-induced gastric lesions were investigated by studying the effect of benzodiazepine ligands on such lesions in both intact and unilaterally vagotomized rats. Clonazepam [5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepine-2-one] a specific central-type receptor agonist (0.625-2.5 mg/kg p.o. or i.p.) and CGS 9896 [2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one] a non-sedative partial agonist with anxiolytic properties (2.5-10 mg/kg p.o.) significantly reduced the gastric damage induced by ethanol (10 ml/kg of a 50% solution v/v p.o.) in non-vagotomized rats but Ro 5-4864 [7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine- 2 -one] a pure peripheral-type receptor agonist (5-20 mg/kg p.o.) failed to affect this damage. The protective action of clonazepam and CGS 9896 against ethanol-induced gastric lesions was blocked, dose dependently, by the central-type receptor antagonist, flumazenil [ethyl 8-fluoro-5,6-5-methyl-6-oxo-4H-imidazo(1,4)f1p4odiazepine-3-carbox ylate] (1.25-20 mg/kg i.p.). In the unilaterally vagotomized rat, ethanol produced lesions in the right (vagotomized) and the left (non-vagotomized) halves of the gastric mucosa to nearly the same extent, while clonazepam and CGS 9896 uniformly decreased the lesions in both halves. It is concluded that central-type benzodiazepine receptors located in the stomach, specifically those mediating the anxiolytic effect of benzodiazepines, are involved in the protective action of benzodiazepines against ethanol-induced gastric lesions.
Khadour
F
F
Department of Pharmacology and Therapeutics, College of Medicine, University of Baghdad, Iraq.
Karim
K
K
Najim
R
R
D000818:Animals; D000431:Ethanol; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D005753:Gastric Mucosa / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D014628:Vagotomy
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D000431:Ethanol