Criteria-based assessment of analgesic activity of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines derivatives based on dataexperimental studies

BACKGROUND: An urgent task in pharmacology is to identify highly effective drugs with analgesic and anti-inflammatory activity. Heterocyclic cyanothioacetamide compounds are of considerable interest. Most authors evaluate the results of studies with separate private indicators of analgesic activity, and their comprehensive criterion assessment is insufficiently defined.

AIM: Development of a criterion assessment in the study of analgesic activity and the establishment of its generalized criteria for samples of chemical compounds of medicinal products.

MATERIALS AND METHODS: The experiments were performed on 390 male rats weighing 250–280 g in the laboratory of the Department of Fundamental and Clinical Pharmacology of St. Luke Lugansk State Medical University. Intact, control and reference (comparison group) groups of ten animals in each group were formed for each pharmacological test. In the intact group, the rats were unharmed. The control group received 2 mL of 0.9% sodium chloride solution intragastrically before each pharmacological test to establish analgesic activity. The reference group was injected with sodium metamizole at a dose of 7 mg/kg intragastrally once 1.5 h before modelling an acute pain reaction. Ten experimental groups were also formed, in which rats were injected with appropriate samples of new original studied derivatives of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridine intragastrically at a dose of 5 mg/kg 1.5 h before modelling acute pain syndrome. Tests for orofacial trigeminal pain, thermal immersion and hot plate were simulated. The indicators of the analgesic effect were the frequency of scratching movements in the orofacial trigeminal pain test and a statistically significant increase in the latent reaction period after the administration of the studied substances in the thermal immersion tests of the tail and hot plate.

RESULTS: The studied samples with ciphers AZ-023, AZ-331 and AZ-383 showed maximum analgesic activity. The proposed criterion of analgesic activity in the experimental groups receiving thienopyridine derivatives with the AZ-023 cipher, according to the results of three tests, was 50.1, exceeding the indicator in the comparison group by 42 times. The values of this criterion in the experimental groups that received new 1,4-dihydropyridine derivatives with laboratory ciphers AZ-331 and AZ-383 for preventive purposes were the maximum in this series of experiments (64.3 and 68.4), which is 53–57 times higher than that of sodium metamizole.

CONCLUSION: The methodology for assessing analgesic activity can be improved based on a criteria-based approach with the aggregation of particular indicators into an abstract model that allows quantifying the degree of analgesic activity. An integral criterion for the analgesic activity of cyanothioacetamide derivatives based on experimental data is proposed. In the future, the proposed approach can be used in studies of various analgesic samples.