Empirical determination of the degree of analgesic activity of some new 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines based on a complex criterion

Abstract

Introduction: It is revelant to solve the problem of anesthesia based on the research of new highly effective and safe medicines. Among modern studies, the preparation of heterocyclic compounds starting from cyanothioacetamide with analgesic and anti-inflammatory activities is of considerable interest. Materials and Methods: The analgesic activity of cyanothioacetamide derivatives was determined on the basis of an integrated approach in three tests: orofacial trigeminal pain, thermal immersion of the tail and in the hot plate test. The experimental characteristics in the studies are quantitative indicators – the frequency of scratching movements n in the first test and the time of the latent period a and t in the second and third tests. Statistical processing consisted in a variance analysis of an array of experimental characteristics. A conditional empirical complex criterion of analgesic activity Anat, inversely proportional to the frequency of scratching movements n and directly proportional to the time of the latent period a and t in the tests is proposed for a comparative assessment of the analgesic activity of the samples. Results: It is shown that all the studied 1,4-dihydropyridines and condensed thieno[2,3-b]pyridines and reveal analgesic activity of varying degrees of severity, based on the values of the criterion Anat. Discussion: It was found that the most pronounced analgesic activity was shown by three studied samples: compounds AZ-023, AZ-331 and AZ-383. The complex criterion of analgesic activity of Anat for animals receiving a sample AZ-023 was 50.1, exceeding the indicator in the comparison group by 42 times. The values of this criterion in animals that had received samples AZ-331 and AZ-383 were the highest, namely 64.3 and 68.4, which is 53 and 57 times higher than that of sodium metamizole, respectively. Conclusion: The obtained results and the advantage of the studied samples over the reference drug determine the expediency of further preclinical studies and a detailed study of their acute and chronic toxicity, as well as hepato-, nephro-, hemato- and gastrotoxicity.

Keywords

• pain syndrome
• analgesic activity
• thieno[2
• 3-b]pyridines
• complex criterion