EXPERIMENTAL STUDY OF THE MEDIATOR MECHANISMS OF THE ANTINOCYCEPTIVE ACTION OF 4-[4-OXO-(4H)-QUINAZOLIN-3-YL]-BENZOIC ACID
Introduction. Previous studies have found that among derivatives of 4-oxo (amino) quinazoline, a leading substance, with pronounced analgesic action on different models of pain perception is 4- [4-oxo-4h-quinazolin-3-yl] benzoic acid (PK-66 compound).
The aim of the study – in-depth study of the main mechanisms involved in the implementation of analgesic action of a new original quinazoline derivative – PK-66 compounds.
Research Methods. Evaluation of the antinociceptive action of PK-66 (1 mg/kg i/h) was studied in rats, modeled on hyperalgesia, caused by the introduction of 0.1 ml of 1 % solution of carrageenin, 2 % suspension of zymosan and 0.01 % solution of bradykinin, which was injected subplantarly in left hind limb of an animal. The degree of nociception was determined using a dollarimeter by estimating the pain threshold. Diclofenac sodium (4 mg/kg) and corvitin (5 mg/kg) were used as reference drugs. The analgesic activity of the test compounds was evaluated by their ability to increase the pain threshold in the study groups compared to the control group and was expressed as a percentage. The anti-exudative activity of the compound and the reference preparations was determined by measuring the volume of paw edema using a plethysmometer. The degree of reduction of swelling in the experimental animals compared to the control group animals and was expressed as a percentage.
Results and Discussion. Compound PK-66 has the ability to eliminate hyperalgesia caused by various algogens. Its most pronounced analgesic effect was manifested against the introduction of bradykinin (53.4 %), less pronounced antinociception was found in carrageenan edema (38.5 %), and the least pronounced effect was on the model of zymosan hyperalgesia (26.9 %). The anti-exudative effect study showed that the degree of antiflogogenic action of PC-66 was more pronounced in the carrageenan swelling model (16.1 %) than zymosan (12.8 %). However, this effect did not reach statistically significant values for either carrageenan or zymosan edema, and in both cases was significantly inferior to the comparison drugs – diclofenac sodium compound (58.3 %) and corvitin (52.3 %).
Conclusion. The anti-mediating effect of PK-66 is more due to antagonism to bradykinin, to a lesser extent to prostaglandins and leukotrienes.
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