| Autor: |
Galenko-Yaroshevsky, Pavel A., Torshin, Ivan Yu., Gromov, Andrei N., Reyer, Ivan A., Gromova, Olga A., Glechyan, Tereza R., Suzdalev, Konstantin F., Zadorozhniy, Andrey V., Zelenskaya, Anait V. |
| Předmět: |
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| Zdroj: |
Research Results in Pharmacology; 2024, Vol. 10 Issue 3, p1-9, 9p |
| Abstrakt: |
Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs. Material and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs. Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2- type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes. Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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