Abstract
The objective of this study was to investigate the effects of 2,3,4-trimethoxy-N'-(8-metyl-8-azabicyclo[3.2.1.] octan-3-ylidene) benzohydrazide hydrochloride (LK-933), a compound of the tropane group with anxiolytic and antimigraine activity, on the levels of monoamines and their metabolites in different brain structures of outbred mice using HPLC–ED. Administration of LK-933 caused an increase in the composite characteristics that describe the rate of dopamine transformation into its metabolites dioxyphenylacetic acid and homovanillic acid in the frontal cortex by 114 and 181%, respectively. The levels of homovanillic acid in the same structure increased by 49%. These data implicate the dopaminergic pathway in the mechanism of LK-933 action.
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Kent, J., Mathew, S., and Gorman, J., Biol. Psychiat., 2002, vol. 52, pp. 1008–1030.
Hoyer, D. and Martin, G., Neuropharmacol., 1997, vol. 36, pp. 419–428.
Clenet, F., Hascoet, M., Fillion, G., Galons, H., and Bourin, M., Behav. Brain Res., 2005, vol. 158, pp. 339–348.
Graeff, F.G., Netto, C.F., and Zangrossi, H., Jr., Neurosci. Behav. Rev., 1998, vol. 23, no. 2, pp. 237–246.
Seredenin, S.B., and Voronin, M.V., Eksp. Klin. Farmakol., 2009, vol. 72, no. 1, pp. 3–10.
Becker, W.J., Headache, 2015, vol. 55, no. 6, pp. 778–93.
Sokolov, A.Yu., Lyubashina, O.A., and Panteleev, S.S., Neurochem. J., 2011, vol. 28, no. 2, pp. 104–112.
Mehrotra, S., Gupta, S., and Chan, K.Y., Naunyn-Schmiedebergs Arch. Pharmacol., 2008, vol. 378, no. 4, pp. 371–394.
Mirzoyan, R.S., Seredenin, S.B., Gan’shina, T.S., Kostochka, L.M., Romanycheva, N.A., and Rusakov, D.Yu., Eksp. Klin. Farmakol., 1998, vol. 61, no. 2, pp. 28–31.
Kozhechkin, S.N., Kostochka, L.M., Bezhanyan, S.G., Mirzoyan, R.S., and Seredenin, S.B., Eksp. Klin. Farmakol., 2005, vol. 68, no. 4, pp. 3–6.
Bernstein, J., and Lott, W.A., US Patent 2838914, 1957.
Kostochka, L.M., Gan’shina, T.S., Naplekova, P.L., Narkevich, V.B., Voronina, T.A., Kudrin, V.S., Mirzoyan R.S., Kurdyumov, I.N., Gudasheva T.A., Zherdev, V.P., and Pyatin B.M., RF Patent application no. 2016133999, 2016.
Raevskii, K.S., Narkevich, V.B., and Klodt, P.M., Eksp. Klin. Farmakol., 2011, vol. 12, pp. 3–7.
De Deurwaerdere, P., Navailles, S., Berg, K.A, Clarke, W.P., and Spampinato, U., J. Neurosci., 2004, vol. 24, pp. 3235–3241.
Raevskii, K.S., Narkevich, V.B., Klodt, P.M., and Kudrin, V.S., Byull. Eksp. Biol. Med., 2012, vol. 153, no. 5, pp. 644–648.
Blackburn, T.P., Suzuki, K., and Ashby, C.R., Jr., Synapse, 2006, vol. 59, pp. 502–512.
Duxon, M.S., Kennett, G.A., Lightowler, S., Blackburn, T.P., and Fone, K.C., Neuropharmacol., 1997, vol. 36, pp. 601–608.
Nutt, D.J., CNS Spectr., 2005, vol. 10, pp. 49–56.
Kennett, G.A, Wood, M.D., Glen, A., Grewal, S., Forbes, I., Gadre, A., and Blackburn, T.P., Br. J. Pharmacol., 1994, vol. 111, pp. 797–802.
Jenck, F., Bos, M., Wichmann, J., Stadler, H., Martin, J.R., and Moreau, J.L., Exper. Opin. Investig. Drugs, 1998, vol. 7, no. 10, pp. 1587–1599.
Pancoesi, A., Cefalalgia, 1997, vol. 17, pp. 3–14.
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Original Russian Text © P.L. Naplekova, V.B. Narkevich, V.S. Kudrin, L.M. Kostochka, T.A. Voronina, 2017, published in Neirokhimiya, 2017, Vol. 34, No. 3, pp. 242–246.
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Naplekova, P.L., Narkevich, V.B., Kudrin, V.S. et al. Neurochemichal aspects of the pharmacological effect of 2,3,4-trimethoxy-N’-(8-methyl-8-azabicyclo[3.2.1.] octan-3-ylidene) benzohydrazide hydrochloride (LK-933). Neurochem. J. 11, 242–245 (2017). https://doi.org/10.1134/S181971241702009X
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DOI: https://doi.org/10.1134/S181971241702009X