A benzodiazepine receptor inverse agonist inhibits stress-induced ulcer formation.
The effects of a benzodiazepine receptor inverse agonist (FG 7142) on gastric ulcer formation were studied in restrained rats. FG 7142 (10-50 mg/kg) reduced in a dose-dependent fashion both the number and cumulative length of gastric ulcers elicited by restraint for 2 hr at 4 degrees C, but did not affect ulcer formation in unrestrained animals maintained in this environment. FG 7142 also reduced gastric ulcer formation in restrained rats maintained at 22 degrees C for 5 hr. The ability of FG 7142 to reduce restraint-stress induced gastric ulcer formation was blocked by the benzodiazepine receptor antagonist ZK 93426 and the beta-adrenoceptor antagonist propranolol. These findings suggest that FG 7142 produces a benzodiazepine-receptor mediated reduction in gastric ulcer formation, which may result from its ability to increase activity of the sympathetic nervous system.
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000473:pathology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000503:physiopathology*
D002243:Carbolines; D011963:Receptors, GABA-A; C035874:FG 7142; D002707:Chlordiazepoxide; C042568:ZK 93426; D011433:Propranolol