Participation of Brain Receptors in the Mechanism of Anticonvulsant Action of a New 4-Benzoylpyridine Oxime Derivative GIZH-298


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Abstract

The aim of the work was to study the involvement of glutamate, dopamine and serotonin receptors in the mechanism of the anticonvulsant action of the 4-benzoylpyridine oxime derivative (GIZh-298). After a single exposure to the cornea with maximum electric shock (MES) and subsequent tonic-clonic seizures, an increase in the density (Bmax) of NMDA receptors in the hippocampus by 27% and a decrease in the number of mGluII receptors (mGluR2/3) by 25% in the prefrontal cortex of the brain of rats are noted. At the same time, the number of 5-HT2A receptors in the prefrontal cortex did not change. GIZh-298 (60 mg/kg) with a single application inhibits convulsive reactions, but does not affect the quantitative changes induced by MES in glutamate receptors and does not affect them under normal conditions, without MES. In tests on mice, subchronic (5 days) corneal exposure to MES reduced the density (Bmax) of D2 receptors in the striatum by 17% and did not change this parameter in the prefrontal cortex. GIZh-298 (60 mg/kg/5 days) eliminates clonic-tonic convulsions in mice and prevents a decrease in the number of D2 receptors from striatal membranes, and also increases their number by 13% in mice without MES in the same structure. The data obtained indicate significant changes in the functional activity of NMDA, mGluII and D2 receptors in the brains of animals that suffered seizures. The anticonvulsant effects of GIZH-298 are accompanied by the restoration of the number of D2 receptors in the striatum..

About the authors

S. A. Litvinova

FSBI “Zakusov Institute of Pharmacology”

Email: nchjournal@gmail.com
Russia, Moscow

E. V. Kondrakhin

FSBI “Zakusov Institute of Pharmacology”

Email: nchjournal@gmail.com
Russia, Moscow

T. A. Voronina

FSBI “Zakusov Institute of Pharmacology”

Email: nchjournal@gmail.com
Russia, Moscow

E. V. Vasilyeva

FSBI “Zakusov Institute of Pharmacology”

Email: nchjournal@gmail.com
Russia, Moscow

G. I. Kovalev

FSBI “Zakusov Institute of Pharmacology”

Email: nchjournal@gmail.com
Russia, Moscow

References

  1. Celli R., Fornai F. // Curr. Neuropharmacol. 2021. V. 19. № 6. P. 747–765.
  2. Alexander G.M., Godwin D.W. // Epilepsy Research. 2006. V. 71. P. 1–22.
  3. Nateri A.S., Raivich G., Gebhardt C., Da Costa C., Naumann H., Vreugdenhil M., Makwana M., Brandner S., Adams R.H., Jefferys J.G., Kann O., Behrens A. // The EMBO Journal. 2007. V. 26. P. 4891–4901.
  4. Doyle S., Pyndiah S., De Gois S., Erickson J.D. // The Journal of Biological Chemistry. 2010. V. 285. P. 14366–14376.
  5. Gangarossa G., Di Benedetto M., O’Sullivan G.J., Dunleavy M., Alcacer C., Bonito-Oliva A., Henshall D.C., Waddington J.L., Valjent E., Fisone G. // PLoS One. 2011. V. 6. e19415.
  6. Gangarossa G., Castell L., Castro L., Tarot P., Veyrunes F., Vincent P., Bertaso F., Valjent E. // Journal of Neurochemistry. 2019. V. 151. P. 204–226.
  7. Glazova M.V., Nikitina L.S., Hudik K.A., Kirillova O.D., Dorofeeva N.A., Korotkov A.A., Chernigovskaya E.V. // Journal of Neurochemistry. 2015. V. 132. P. 218–229.
  8. Jiang W., Van Cleemput J., Sheerin A.H., Ji S.P., Zhang Y., Saucier D.M., Corcoran M.E., Zhang X. // Journal of Neuroscience Research. 2005. V. 81. P. 581–588.
  9. Bozzi Y., Borrelli E. // Frontiers in Cellular Neuroscience. 2013. V. 7. P. 157.
  10. Aghajanian G.K., Marek G.J. // Brain Res. 1999. V.825 (1–2). P. 161–71.
  11. Celada P., Puig M.V., Artigas F. // Frontiers in Integrative Neuroscience. 2013. V. 7. Article 25.
  12. Crunelli V. et al. // Xjenza Online. 2017. V. 5. P. 3–14.
  13. Crunelli V., Di Giovanni G. // CNS Neurosci. Ther. 2021. V. 12. P. 967–970.
  14. Жмуренко Л.А., Воронина Т.А., Литвинова С.А., Неробкова Л.Н., Гайдуков И.О., Мокров Г.В., Гудашева Т.А. // Химико-фармацевтический журнал. 2018. Т. 52. № 1. С. 19–28.
  15. Gaydukov I.O., Voronina T.A, Litvinova S.A., Kutepova I.S. // Medicinal Chemistry Research. 2020. V. 29. P. 783–792.
  16. Литвинова С.А., Наркевич В.Б., Гайдуков И.О., Кудрин В.С., Воронина Т.А. // Нейрохимия. 2019. Т. 36. № 3. С. 239–245.
  17. Воронина Т.А., Неробкова Л.Н. // Руководство по проведению доклинических исследований лекарственных средств. Часть.1. ФГБУ “НЦЭМСП”. М.: Гриф и К, 2012. Глава 14. С. 235–250.
  18. Leysen J.E., Niemegeers C.J. // Mol. Pharmacol. 1982. V. 21. № 2. P. 301–14.
  19. Zhou L.M., Gu Z.Q., Costa A.M., Yamada K.A., Manssone P.E. // J. Farm. Exp. Ter. 1997. V. 280(1). P. 422–427.
  20. LaPage K.T., Ishmael J.E., Low C.W., Traynelis S.F., Murray T.F. // Neuropharm. 2005. V. 49. P. 1–16.
  21. Schaffhauser H., Richards J.G., Cartmell J., et al. // Mol. Pharmacol. 1998. V. 53. P. 228–233.
  22. Sun W., Ginovart N., Ko F., Seeman P., Kapur S. // Mol. Pharmacol. 2003. V. 63. № 2. P. 456–462.
  23. Naylor D.E., Liu H., Niquet J., et al. // Neurobiol. Dis. 2013. V. 54. P. 225–238.
  24. Jaideep Kapur. // Epilepsia Open. 2018. V. 3. P. 165–168.
  25. Garrido-Sanabria E.R., Otalora L.F., Arshadmansab M.F., Herrera B., Francisco S., Ermolinsky B.S. // Brain Res. 2008. V. 13. P. 165– 176.
  26. Watanabe Y., Kaida Y., Fukuhara S., Takechi K., Uehara T., Kamei C. // Epilepsia. 2011. V. 52. P. 140–150.
  27. Doherty J.J., Alagarsamy S., Bough K.J., Conn P.J., Dingledine R., Mott D.D. // J. Physiol. 2004. V. 2. P. 395–401.
  28. Bocchio M., Lukacs I.P., Stacey R., Plaha P., Apostolopoulos V., Livermore L., Sen A., Ansorge O., Gillies M.J., Somogyi P., Capogna M. // Front. Cell Neurosci. 2018. V. 12. P. 508.
  29. Mathern G.W., Pretorius J.K., Kornblum H.I., et al. // Brain. 1997. V. 120. P. 1937–1959.
  30. Mathern G.W., Pretorius J.K., Mendoza D., et al. // J. Neuropathol. Exp. Neurol. 1998. V. 57. P. 615—634.
  31. Bagdy G., Kecskemeti V., Riba P., Jakus R. // J. Neurochem. 2007. V. 100. № 5. P. 857– 873.
  32. Asano E., Chugani D.C., Muzik O., Shen C., Juhasz C., Janisse J., Ager J., Canady A., Shah J.R., Shah A.K., Watxon C., Chugani H.T. // Neurology. 2000. V. 54. P. 1976–1984.
  33. Fedi M., Reutens D., Okazawa H., Andermann F., Boling W., Dubeau F., White C., Nakai A., Gross D.W., Andermann E., Diksic M. // Neurology. 2001. V. 57. P. 1629–1636.
  34. Chugani D.C. // Biomark. Med. 2011. V. 5. № 5. P. 567–575.
  35. Jiang X., Xing G., Yang C., Verma A., Zhang L. & Li H. // Neuropsychopharmacology. 2009. V. 34. P. 410–423.
  36. Raote I., Bhattacharya A., Panicker M.M. // In Chattopadhyay A, editor. Serotonin Receptors in Neurobiology. CRC Press/Taylor & Francis. 2007. Chapter 6.
  37. Beaulieu J.M., Gainetdinov R.R. // Pharmacological Reviews. 2011. V. 63. P. 182—217.
  38. Lalchandani R.R., van der Goes M.S., Partridge J.G., Vicini S. // J. Neurosci. 2013. V. 33. P. 14075–14086.
  39. Landvogt C., Buchholz H.G., Bernedo V., Schreckenberger M., Werhahn K.J. // Epilepsia. 2010. V. 51. P. 1699–1706.
  40. Yakushev I.Y., Dupont E., Buchholz H.-G., Tillmanns J., Debus F., Cumming P., Heimann A., Fellgiebel A., Luhmann H.J., Landvogt C., Werhahn K.J., Schreckenberger M., Potschka H., Bartenstein P. // Epilepsia. 2010. V. 51. P. 415–422.
  41. Rocha L., Alonso-Vanegas M., Villeda-Hernández J., Mújica M., Cisneros-Franco J.M., López-Gómez M., Zavala-Tecuapetla C., Frías-Soria C.L., Segovia-Vila J., Borsodi A. // Neurobiol. Dis. 2012. V. 45. P. 499–507.
  42. Bernedo Paredes V.E., Buchholz H.G., Gartenschläger M., Breimhorst M., Schreckenberger M., Werhahn K.J. // PLoS One. 2015. V. 10. e0141098.
  43. Dorofeeva N.A., Grigorieva Y.S., Nikitina L.S., Lavrova E.A., Nasluzova E.V., Glazova M.V., Chernigovskaya E.V. // Neurological Research. 2017. V. 39. P. 918–925.
  44. Strome E.M., Zis A.P., Doudet D.J. // J. Psychiatry Neurosci. 2007. V. 32. P. 193–202.
  45. Landau A.M., Chakravarty M.M., Clark C.M., Zis A.P., Doudet D.J. // Neuropsychopharmacology. 2011. V. 36. P. 511–518.
  46. Khan T.A., Momin W.M., Phadke A.G. // Journal of Contemporary Medicine and Dentistry. 2014. V. 2. P. 29–32.

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Copyright (c) 2023 С.А. Литвинова, Е.А. Кондрахин, Т.А. Воронина, Е.В. Васильева, Г.И. Ковалев