F. Khadour et al., DRUGS ACTING AT CENTRAL BENZODIAZEPINE RECEPTORS ATTENUATE ETHANOL-INDUCED GASTRIC-LESIONS IN RATS, European journal of pharmacology, 298(3), 1996, pp. 271-277
The characteristics of the receptors involved in the protective action
of benzodiazepines against ethanol-induced gastric lesions were inves
tigated by studying the effect of benzodiazepine ligands on such lesio
ns in both intact and unilaterally vagotomized rats. Clonazepam )-1,3-
dihydro-7-nitro-2H-1,4-benzodiazepine-2-one] a specific central-type r
eceptor agonist (0.625-2.5 mg/kg p.o. or i.p.) and CGS 9896 yl)-2,5-di
hydropyrazolo(4,3-c)quinoline-3(3H)-one] a non-sedative partial agonis
t 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 -1,3-dihydro-1-methyl-2H-
1,4-benzodiazepine-2-one] a pure peripheral-type receptor agonist (5-2
0 mg/kg p.o.) failed to affect this damage. The protective action of c
lonazepam and CGS 9896 against ethanol-induced gastric lesions was blo
cked, dose dependently, by the central-type receptor antagonist, fluma
zenil [ethyl 6-oxo-4H-imidazo(1,4)benzodiazepine-3-carboxylate] (1.25-
20 mg/kg i.p.). In the unilaterally vagotomized rat, ethanol produced
lesions in the right (vagotomized) and the left (non-vagotomized) halv
es of the gastric mucosa to nearly the same extent, while clonazepam a
nd CGS 9896 uniformly decreased the lesions in both halves. It is conc
luded that central-type benzodiazepine receptors located in the stomac
h, specifically those mediating the anxiolytic effect of benzodiazepin
es, are involved in the protective action of benzodiazepines against e
thanol-induced gastric lesions.