Comparative assessment of the analgetic activityof new partially hydrogenated pyridines, α-cyanothioacetamidederivatives, in experiments of orofacial trigeminal pain and hot plate test

Introduction: Experimental studies were carried out to determine the antinociceptive activity of new partially hydrogenated pyridines, α-cyanothioacetamide derivatives, in experiments of orofacial trigeminal pain and hot plate test, implemented on white outbred laboratory rats. Materials and Methods: Controlled randomized studies of orofacial trigeminal pain and hotplate were carried out on white outbred laboratory rats in the conditions of the scientificresearch laboratory of Saint Luka Lugansk State Medical University of the Ministry of Health of the Russian Federation. New partially hydrogenated pyridines, α-cyanothioacetamide derivatives(α-CTA) with laboratory codes cv-091, cv-095, cv-099, and cv-142, which are promisingconsidering preliminary studies in silico, were used as test samples. The analgesics metamizolesodium and mefenamic acid were used as comparison drugs. The experiment was implementedon 128 outbred sexually mature male rats. The animals received experimental samples andreference drugs intragastrically. Statistical processing of experimental data was carried out usingthe nonparametric Wilcoxon T-test. The normality of the distribution was determined using the Shapiro-Wilk criterion. Results: According to the data obtained during the experiment, it was determined that newpartially hydrogenated pyridines, α-cyanothioacetamide derivatives, with laboratory codes cv-091, cv-095, cv-099, cv-142, have analgesic activity, which is confirmed by a decrease in the dynamics of the number of scratching movements of the vibrissae area with the front paws in rats, relative to the control group, as well as prolonging the nociceptive response time in the hotplate test. Discussion: In the course of the experimental study, data were obtained indicating thepresence of pronounced analgesic activity in new partially hydrogenated pyridines, α-cyanothioacetamide derivatives (α-CTA). The biological activity of compounds with the lab codescv-091, cv-095, cv-099, and cv-142 is confirmed by data obtained in preliminary studies in silico-biological screening, where the main biological targets that determine the antinociceptiveactivity of the studied compounds are identified. The leading sample in orofacial trigeminal painand hot plate tests is compound cv-099, injected intragastrically at a dosage of 5 mg per kg of animal body weight. Conclusion: New partially hydrogenated pyridines, α-cyanothioacetamide derivatives, showedpronounced antinociceptive activity at a dosage of 5 mg per kg of animal body weight with a single intra-gastric injection in experiments of orofacial trigeminal pain and a hot plate test,which is confirmed by the results obtained during the tests. Compounds with laboratory codescv-091, cv-095, cv-099, cv-142 are recommended for further preclinical studies due to theirpractical prospects.