Assessment of pharmacological activity and bioavailability of the new derivative 1,3,4-thiadiazole

Abstract

Introduction: Acexazolamide is a new derivative of 1,3,4-thiadiazole and acexamic acid.

Materials and methods: In animal experiments, acute toxicity, pharmacological activity and bioavailability of acexazolamide were evaluated. Anti-inflammatory activity was assessed on the model of formalin edema of paw and cotton pellet granuloma in rats. Assessment of analgesic activity was carried out in a hot plate test in mice, chemical pain stimulation of the peritoneum and inflammatory hyperalgesia in rats. The antipyretic activity of acexazolamide was evaluated in a model of yeast-induced hyperthermia in rats. The anti-burn activity of acexazolamide was evaluated in a thermal skin burn model in rats. Bioavailability of acexazolamide with intragastric administration was determined in rabbits. The content of acetaxazolamide in blood plasma was determined by HPLC-MS/MS method.

Results and discussion: DL₅₀ of acexazolamide after intragastric administration to mice was 860.99 (95% CIs, 462.2 to 1259.8) mg/kg. The anti-inflammatory activity of acexazolamide (21.5 mg/kg) with formalin-induced paw edema and fetal granuloma in rats was higher than that of ketoprofen (23.0 mg/kg). ED₅₀ value for analgesic activity with acetic acid induced cortex was 24.99 (95% CIs: 15.31–34.68) mg/kg. With thermal stimulation of the paw in mice, the ED₅₀ value was 25.56 (95% CIs: 15.13 to 35.98) mg/kg. ED₅₀ value for antipyretic activity was 31.85 (95% CIs: 19.22–44.47) mg/kg. Acexazolamide (21.5 mg/kg) had a stimulating effect on the regeneration of damaged tissues in case of thermal skin burns. Bioavailability of acexazolamide (1 mg/kg) with intragastric administration was 37%.

Conclusion: Acexazolamide has the properties of a non-steroidal anti-inflammatory agent.