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BENZODIAZEPINES REDUCE GASTRIC ULCERS INDUCED IN RATS BY STRESS

1 The sedative and antiulcer effects of chlordiazepoxide (5 to 50 mg/kg) and lorazepam (0.25 to 2.5 mg/kg) were investigated in the rat. 2 Sedation was measured by recording locomotor activity in a holeboard. Ulceration of the glandular stomach was induced by a 2 h period of restraint at 4°C. 3 Acutely, both drugs produced significant sedation at all doses; high doses only (chlordiazepoxide 10 and 50 mg/kg; lorazepam 2.5 mg/kg) produced a significant reduction in ulcer formation. 4 With chronic treatment, after 5 and 10 days administration of chlordiazepoxide (50 mg/kg), tolerance to sedation was observed without a similar change in antiulcer action. 5 Cimetidine (20 mg/kg) and atropine (0.2 mg/kg) decreased ulcer formation without causing sedation. 6 The antisecretory profile of chlordiazepoxide (2 × 10−4m), in the rat isolated gastric mucosa, resembled that of atropine (10−7 m) rather than cimetidine (10−5 m). 7 These observations suggest that the antiulcer effect of benzodiazepines probably results from a combination of sedative, anxiolytic and antisecretory actions.