Study the efficiency of a natural ligand of a protono-aсtivated receptors on biomodels of somatic pain

Natural ligands protono-aсtivated receptors were studied by biomodel (hypersensitivity provoked by CFA and visceral pain) assessment of somatic pain. Peptide UGTX study pharmacological activity after intramuscular hypersensitivity tests provoked CFA, and visceral pain, showed the maximum analgesic activity at a dose of 0.02 mg / kg. Increasing or decreasing the dose of UGTX peptide was not significantly different from the reference drug. Sevanol 1 mg / kg showed comparable diclofenac analgesic activity, but at a dose of 10 mg / kg of diclofenac significantly superior in terms of reduction of the total number of cramps. The studied ligands may be considered as potential analgesic drugs.

ASICs, in vivo модели, ASICs, natural ligands, in vivo models, analgesic activity

1. Бондаренко Д.А., Дьяченко И.А., Скобцов Д.И., Мурашев А.Н. In vivo модели для изучения анальгетической активности // Биомедицина. 2011. № 2. С. 84-94.

2. Руководство по проведению доклинических исследований лекарственных средств. Ч. 1. - М.: Гриф и К. 2012. 944 с.

3. Яшин В.И., Веденин А.Н., Яшин А.Я. Антиоксиданты и спорт. Основные причины неудачных применений, возможные перспективы // Спортивная медицина: наука и практика. 2016. № 1. С. 35-39.

4. Deval E., Noël J., Gasull X., Delaunay A., Alloui A., Friend V., Eschalier A., Lazdunski M., Lingueglia E. Acid-sensing ion channels in postoperative pain // J. Neurosci. 2011. No. 31. P. 6059-6066.

5. Dubé G.R., Lehto S.G., Breese N.M., Baker S.J., Wang X., Matulenko M.A., Honoré P., Stewart A.O., Moreland R.B., Brioni J.D. Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels // Pain. 2005. No. 117(1-2). P. 88-96.

6. Dubinnyi M.A., Osmakov D.I., Koshelev S.G., Kozlov S.A., Andreev Y.A., Zakaryan N.A., Dyachenko I.A., Bondarenko D.A., Arseniev A.S., Grishin E.V. Lignan from thyme possesses inhibitory effect on ASIC3 channel current // J. Biol. Chem. 2012. No. 287. P. 32993-33000.

7. Gautam M.I., Benson C.J., Ranier J.D., Light A.R., Sluka K.A. ASICs do not play a role in maintaining hyperalgesia induced by repeated intramuscular acid injections // Pain Res. Treat. 2012:817347. doi: 10.1155/2012/817347.

8. Karczewski J., Spencer R.H., Garsky V.M., Liang A., Leitl M.D., Cato M.J., Cook S.P., Kane S., Urban M.O. Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2 // Br. J. Pharmacol. 2010. No. 161. P. 950-960.

9. Mogil J.S., Breese N.M., Witty M.F., Ritchie J., Rainville M.L., Ase A., Abbadi N., Stucky C.L., Séguéla P. Transgenic expression of a dominant-negative ASIC3 subunit leads to increased sensitivity to mechanical and inflammatory stimuli // J. Neurosci. 2005. No. 26;25(43). P. 9893-901.

10. Osmakov D.I., Kozlov S.A., Andreev Y.A., Koshelev S.G., Sanamyan N.P., Sanamyan K.E., Dyachenko I.A., Bondarenko D.A., Murashev A.N., Mineev K.S., et al. Sea anemone peptide with uncommon β-hairpin structure inhibits acid-sensing ion channel 3 (ASIC3) and reveals analgesic activity // J. Biol. Chem. 2013. No. 288. P. 23116-23127.

11. Sluka K.A., Winter O.C., Wemmie J.A. Acid-sensing ion channels: A new target for pain and CNS diseases // Curr. opin. drug discov. devel. 2009. No. 12. P. 693-704.

12. Wemmie J.A., Askwith C.C., Lamani E., Cassell M.D., Freeman J.H., Welsh M.J. Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning // J. Neurosci. 2003. No. 23. P. 5496-5502.