EXPERIMENTAL STUDY OF ULCEROGENIC ACTION OF PROPOXAZEPAM

In experiments on 94 white male rats in the Wistar line, were studied changes in the gastric mucous under the acute, subchronic and chronic conditions after introduction of a new original derivative of benzodiazepine – proxazepam. The study of gastrotoxicity of propoxazepam was carried out under conditions of its intragastric administration with Tween-80 solvents and distilled water. It has been established that propoxazepam does not exhibit a damaging effect on the stomach in the conditions of acute (3 hours after, 50, 250, 500 and 1000 mg/kg perorally), as well as subacute (within 4 days, 50 mg/kg perorally) and chronic (within 28 days, 0,5 mg/kg perorally) administration, and also does not change the dietary behavior and general activity of animals, which is confirmation of harmlessness of this compound, in particular, on the gastrointestinal tract.

Thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole derivatives of isonicotinic acid hydrazide: Synthesis and their biological evaluation

A series of thiazolidin-4-one (2a-h, 3a-h), azetidin-2-one (4a- h) and 1,3,4-oxadiazole (5a-h) derivatives of isoninicotinic acid hydrazide (INH) were synthesized in order to obtain new compounds with potential anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities. The structures of the new compounds were supported by their IR, 1H-NMR and mass spectral data. All compounds were evaluated for their anti-inflammatory activity by the carrageenan-induced rat paw edema test method. Eleven of the new compounds, out of 32, showed very good anti-inflammatory activity in the carrageenan-induced rat paw edema test, with significant analgesic activity in the tail immersion method together with negligible ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the by-products of lipid peroxidation. The study showed that the compounds inhibited the induction of gastric mucosal lesions and it can be suggested from the results that their protective effects may be related to inhibition of lipid peroxidation in the gastric mucosa.