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Effect of Mexidol and Nitroxymexidol on Phosphodiesterase Activity, Some Oxidation Processes, and Hypoxia Resistance

  • MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION
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Pharmaceutical Chemistry Journal Aims and scope

The effect of mexidol (M) and nitroxymexidol (NM) on the activity of phosphodiesterase of cyclic guanosine monophosphate (PDEcGMP), regulation of lipid peroxidation (LPO), and antiradical and antihypoxic activity was investigated under normoxia and normobaric hypercapnic hypoxia conditions. Reversible and noncompetitive inhibition of the hydrolytic function of PDEcGMP by M and NM was revealed. The Ki value for M was 1 ×10–4 M; for NM, 1 ×10–5 M, i.e., NM was 10 times more active than M. It was shown that the lifetime of experimental animals in a closed space increased by 36% under the action of M as compared with that of the control group while it increased by 53% for NM. The ventricular contraction time increased by 137% for NM. The atrial contraction time increased from 31 min in the control to 52 and 57 min for M and NM, respectively.

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References

  1. T. N. Roudneva, N. Sanina, D. Mischenko, et al., Nitric Oxide: Biol. Chem., 19, Supplement, 43 (2008).

  2. L. V. Tat’yanenko, O. V. Dobrokhotova, R. A. Kotel’nikov, et al., Pharm. Chem. J., 45(6), 329 – 332 (2011).

    Article  Google Scholar 

  3. L. M. Baider, O. L. Belaya, Z. V. Kuropteva, et al., Vopr. Biol. Med. Farm. Khim., No. 3, 44 – 47 (2009).

  4. R. G. Glushkov, S. D. Yuzhakov, M. V. Alekseev, et al., Khim.-farm. Zh., 45(3), 3 – 8 (2011); Pharm. Chem. J., 45(3), 131 –136 (2011).

    Article  CAS  Google Scholar 

  5. B. S. Fedorov, M. A. Fadeev, V. N. Varfolomeev, et al., RU Pat. No. 2,394,815, Jul. 20, 2010, “Nitroxy-succinate 2-ethyl-6-methyl-3-oxypyridine (versions of use) and method for producing said compound.”

  6. V. K. Promonenkov and V. P. Rutkovskij, RU Pat. No. 2,211,833, Sep. 10, 2003, “Method for preparing 2-ethyl-6-methyl-3-hydroxy-pyridine.”

  7. R. E. Liberzon, T. T. Shchekoldina, and O. S. Vatolkina, Vopr. Med. Khim., 4, 526 – 530 (1977).

    Google Scholar 

  8. J. L. Bailey, Techniques in Protein Chemistry, Elsevier Pub. Co., New York (1967) [Russian translation pp. 53 – 60].

    Google Scholar 

  9. I. B. Berezin and A. A. Khlesov, Practical Course in Chemical and Enzyme Kinetics [in Russian], Izd. MGU, Moscow (1976), pp. 77 – 84.

    Google Scholar 

  10. R. A. Kotel’nikova, D. V. Mishchenko, D. A. Zhokhova, et al., High Energy Chem., 43(7), 582 – 586 (2010).

    Article  Google Scholar 

  11. T. F. Slater, Methods Enzymol., 105, 283 – 293 (1984).

    Article  CAS  PubMed  Google Scholar 

  12. R. F. Kotel’nikova and I. I. Faingol’d, Izv. Akad. Nauk, Ser. Khim., 6, 1146 – 1150 (2011).

    Google Scholar 

  13. F. Rind, Mod. Drug Discovery, Nov / Dec, 31 (1998).

  14. V. G. Granik and N. B. Grigor’ev, Izv. Akad. Nauk, Ser. Khim., 8, 1268 – 1272 (2002).

    Google Scholar 

  15. V. G. Granik and N. B. Grigor’ev, Nitric Oxide (NO). New Pathway to Drug Discovery [in Russian], Vuzovskaya Kniga, Moscow (2004), p. 360.

    Google Scholar 

  16. R. A. Kotel’nikova, I. I. Faingold, D. A. Poletaeva, et al., Russ. Chem. Bull., 60(6), 1172 – 1176 (2011).

    Article  Google Scholar 

  17. A. I. Kotel’nikov, G. N. Bogdanov, D. V. Mishchenko, et al., Al’manakh Klin. Med., 1(17), 199 – 200 (2008).

    Google Scholar 

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Correspondence to D. V. Mishchenko.

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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 48, No. 7, pp. 3 – 6, July, 2014.

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Tat’yanenko, L.V., Dobrokhotova, O.V., Varfolomeev, V.N. et al. Effect of Mexidol and Nitroxymexidol on Phosphodiesterase Activity, Some Oxidation Processes, and Hypoxia Resistance. Pharm Chem J 48, 417–420 (2014). https://doi.org/10.1007/s11094-014-1123-6

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  • DOI: https://doi.org/10.1007/s11094-014-1123-6

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