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Neurotropic, Psychoactive, and Analgesic Properties of Benzimidazole and Its Derivatives: Physiological Mechanisms

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This review summarizes current data and the results of the authors’ own investigations of the neurotropic, psychoactive, and analgesic properties of benzimidazole and its derivatives. Using a series of compounds of this class as a examples, different aspects of the actions of benzimidazoles on the nervous system of lab animals (mollusks, mice, rats, cats) are considered. The efficacy of benzimidazoles is shown to be due to actions on a number of important physiological mechanisms regulating the functional state of nerve cells and neurotransmitter systems, inflammation processes, and pain.

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References

  1. S. B. Seredenin, Yu. D. Ignatov, A. I. Vislobokov, et al., “Effects of Afobasol on transmembrane ion current in mollusk neurons,” Eksperim. Klin. Farmakol., 68, No. 5, 3–6 (2005).

    CAS  Google Scholar 

  2. A. I. Vislobokov, Yu. D. Ignatov, and S. B. Seredenin, “Changes in the electrical activity of neurons in the presence of Afobasol,” Eksperim. Klin. Farmakol., 75, No. 6, 3–7 (2012).

    CAS  Google Scholar 

  3. A. I. Vislobokov, K. N. Mel’nikov, and P. D. Shabanov, “Changes in ion currents in neurons on extra- and intracellular exposure to Afobasol and bupivacaine,” Obz. Klin. Farmakol. Lekarst. Ter., 12, No. 3, 50–55 (2014).

    Article  Google Scholar 

  4. A. P. Galenko-Yaroshevskii, L. L. Katalymov, V. V. Shurekov, and A. V. Kiselev, “Decreases in the pH of the external solution slow the rate of blockade of the conductivity of A-fibers of the sciatic nerve by the imidazobenzimidazole derivative RU-1117,” Kubansk. Nauchn. Med. Vestn., 113, No. 8, 29–33 (2009).

    Google Scholar 

  5. A. P. Galenko-Yaroshevskii, L. L. Katalymov, V. V. Shurekov, and A. V. Kiselev, “Decreases in the pH of the external solution weakens blockade of the conductivity of A-fibers of the sciatic nerve by the imidazobenzimidazole derivative RU-353,” Kubansk. Nauchn. Med. Vestn., 113, No. 8, 33–36 (2009).

    Google Scholar 

  6. T. V. Gamma, “Behavioral reactions of rats on exposure to various benzimidazole derivatives at ultra-low concentrations,” Uchen. Zap. Tavrich. Nats. Univ. im. Vernadskogo. Ser. Biol. Khim., 26, No. 1, 30–36 (2013).

    Google Scholar 

  7. T. V. Gamma, I. V. Epishkin, I. I. Korenyuk, et al., “Psychotropic effects of benzimidazole in experimental models of stress in rats,” Uchen. Zap. Tavrich. Nats. Univ. im. Vernadskogo. Ser. Biol. Khim., 22, No. 2, 16–23 (2009).

    Google Scholar 

  8. T. V. Gamma and I. I. Korenyuk, “Effects of Bemitil and benzimidazole on the behavior of rats in the open field test,” Neirofiziologiya, 38, No. 1, 71–76 (2006).

    Google Scholar 

  9. T. V. Gamma, I. I. Korenyuk, D. R. Khusainov, et al., “Analgesic properties of benzimidazole,” Uchen. Zap. Tavrich. Nats. Univ. im. Vernadskogo. Ser. Biol. Khim., 23, No. 2, 66–71 (2010).

    Google Scholar 

  10. O. Yu. Grechko, A. A. Spasov, D. M. Shtareva, and A. I. Rashchenko, “Studies of the receptor mechanism of the analgesic actions of compound RU-1205,” Vestn. Volgograd. Gos. Med. Univ., 1, No. 49, 61–63.

  11. A. V. Kataev and T. R. Gizatullin, “Effects of a benzimidazole derivative containing a dioxothietane ring on the sequelae of psychoemotional stress induced in animals by physical loading,” Kazan. Med. Zh., 96, No. 1, 56–60 (2015).

    Article  Google Scholar 

  12. O. I. Kolotilova and I. I. Korenyuk, “Effects of Bemitil on the electrical activity of the aminergic systems and cerebral cortex in conscious cats,” Neirofiziologiya, 41, No. 3, 218–225 (2009).

    Google Scholar 

  13. O. I. Kolotilova, V. B. Pavlenko, A. M. Kulichenko, et al., “Effects of Bemitil on the activity of the noradrenergic and serotoninergic neurons in the brainstem and the EEG in conscious cats,” Neirofiziologiya, 37, No. 3, 235–243 (2005).

    Google Scholar 

  14. I. I. Korenyuk, T. V. Gamma, D. R. Khusainov, et al., Neurotropic Effects of Chemical Compounds of Different Classes and the Possible Mechanisms of their Actions, DIAIPI, Simferopol (2012).

    Google Scholar 

  15. Yu. A. Polkovnikova, E. F. Stepanova, O. S. Gudyrev, and M. V. Pokrovskii, “A comparative study of the parameters of orientational behavior and emotionality in rats in the open field test on exposure to original medicinal formulations of Afobasol,” Vestn. Voronezh. Gos. Univ. Ser. Khim. Biol. Farm., No. 1, 192–195 (2011).

    Google Scholar 

  16. F. G. Razumnaya, F. Kh. Kamilov, O. M. Kapuler, and N. A. Mufazalova, “The pharmacology of Afobasol,” Fundam. Issled., 7, 848–855 (2014).

    Google Scholar 

  17. S. B. Seredenin and M. V. Voronin, “Neuroreceptor mechanisms of action of Afobasol (a discussion),” Zh. Psikhiatr. Psikhofarmakoter., 15, No. 1, 59–61 (2013).

    Google Scholar 

  18. S. B. Seredenin, Yu. D. Ignatov, M. A. Yarkova, et al., “Effects of Afobasol on transmembrane ion currents in neurons in a mollusk,” Eksperim. Klin. Farmakol., 68, No. 5, 3–6 (2005).

    CAS  Google Scholar 

  19. S. B. Seredenin and V. A. Kraineva, “Neuroprotective properties of Afobasol in repeated modeling of hemorrhagic stroke in elderly rats,” Eksperim. Klin. Farmakol., 72, No. 1, 24–28 (2009).

    CAS  Google Scholar 

  20. I. V. Silkina, T. S. Gan’shina, S. B. Seredenin, and R. S. Mirzoyan, “A GABAergic mechanism for the cerebrovascular and neuroprotective effects of Afobasol and Picamilon,” Eksperim. Klin. Farmakol., 68, No. 1, 20–24 (2005).

    CAS  Google Scholar 

  21. A. A. Spasov, K. Yu. Kalitin, O. Yu. Grechko, and V. A. Anisimova, “Antiepileptic activity of the new benzimidazole derivative RU-1205,” Byull. Eksperim. Biol. Med., 160, No. 9, 320–323 (2015).

    Google Scholar 

  22. A. A. Spasov, L. A. Smirnova, O. Yu. Grechko, et al., “Pharmacokinetic and analgesic effects of an injectable formulation of the new imidazobenzimidazole compound RU-1205 with κ agonist activity,” Biomed. Khim., 61, No. 5, 636–639 (2015).

    Article  CAS  Google Scholar 

  23. A. A. Spasov, M. V. Chernikov, and S. T. Kiabiya, “Analgesic activity of 5-HT3 receptor antagonists,” Byull. Eksperim. Biol. Med., 139, No. 4, 416–419 (2005).

    Google Scholar 

  24. A. A. Spasov, M. V. Chernikov, D. S. Yakovlev, and V. A. Anisimova, “Studies of the antiserotonin activity of derivatives of tricyclic benzimidazole systems,” Khim.-Farm. Zh., 40, No. 11, 23–26 (2006).

    Google Scholar 

  25. I. A. Tregubova, V. A. Kosolapov, A. A. Spasov, and V. A. Anisimova, “Experimental study of the effects of a new antioxidant substance on learning and memory,” Byull. Eksperim. Biol. Med., 156, No. 12, 757–759 (2013).

    Google Scholar 

  26. I. V. Cheretaev, “Effects of ultra-low concentrations of 2-aminomethylbenzimidazole on behavior in rats in the Porsolt test in health and on the background of activation of the dopaminergic system with Yumex,” Molodoi Uchenyi, 19, No. 78, 100–104 (2014).

    Google Scholar 

  27. I. V. Cheretaev and I. V. Epishkin, “Comparison of the antistress and anxiolytic effects of ultra-low concentrations of 2-aminomethylbenzimidazole and Sibazon in the behavior open field test,” in: 78th Summary Sci.-Applied Conference, Krasnoyarsk (2014), pp. 706–708.

  28. I. V. Cheretaev, I. I. Korenyuk, T. V. Gamma, and D. R. Khusainov, “Effects of ultra-low concentrations of benzimidazole on the behavior of rats in the Porsolt test in normal conditions and on the background of activation of the dopaminergic system with Yumex,” Uchen. Zap. Tavrich. Nats. Univ. im. Vernadskogo. Ser. Biol. Khim., 27, No. 4, 93–99 (2014).

    Google Scholar 

  29. K. C. Achar, K. M. Hosamani, and H. R. Seetharamareddy, “In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives,” Eur. J. Med. Chem., 45, No. 5, 2048–2054 (2010).

    Article  CAS  Google Scholar 

  30. S. Dixit, P. K. Sharma, and N. Kaushik, “Synthesis of novel benzimidazole derivatives: as potent analgesic agent,” Med. Chem. Res., 22, No. 2, 900–904 (2013).

    Article  CAS  Google Scholar 

  31. T. V. Gamma, I. I. Korenyuk, M. Y. Baevsky, et al., “Effects of Some Benzimidazole Derivatives on Electrical Activity in Molluscan Neurons,” Neurophysiology, 34, No. 2–3, 147–149 (2002).

    Google Scholar 

  32. T. V. Hamma and I. I. Koreniuk, “Effect of benzimidazole and its derivatives on electrical activity of Helix albescens Rossm. neurons and behavior of rats,” Fiziol. Zh., 53, No. 5, 53–66 (2007).

    CAS  PubMed  Google Scholar 

  33. M. Hasegawa, N. Nishigaki, Y. Washio, et al., “Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors,” J. Med. Chem., 50, No. 18, 4453–4470 (2007).

    Article  CAS  Google Scholar 

  34. R. S. Keri, A. Hiremathad, S. Budagumpi, and B. M. Nagaraja, “Comprehensive review in current developments of benzimidazole-based medicinal chemistry,” Chem. Biol. Drug Des., 86, No. 1, 19–65 (2015).

    Article  Google Scholar 

  35. I. I. Kolotilova, I. I. Koreniuk, and Y. O. Fokina, “Modification of impulse activity of cat brainstem monoaminergic cells caused by Bemitil,” Fiziol. Zh., 54, No. 5, 71–74 (2008).

    CAS  PubMed  Google Scholar 

  36. S. Kostic-Rajacic, V. Šoškic, and J. Joksimovic, “Mixed dopaminergic/ serotonergic properties of several 2-substituted 4-[2-(5-benzimidazole) ethyl]-1-arylpiperazines,” Archiv der Pharmazie, 331, No. 1, 22–26 (1998).

    Article  CAS  Google Scholar 

  37. G. Mariappan, R. Hazarika, F. Alam, et al., “Synthesis and biological evaluation of 2-substituted benzimidazole derivatives,” Arabian. J. Chem., 8, No. 5, 715–719 (2015).

    Article  CAS  Google Scholar 

  38. B. G. Mohamed, M. Abdel-Alim, and M. Hussein, “Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal, anti-inflammatory and analgesic effects,” Acta Pharmacol., 56, No. 1, 31–48 (2006).

    CAS  Google Scholar 

  39. A. A. Spasov, I. N. Ijozhitsa, L. I. Bugaeva, and V. A. Anisimova, “Benzimidazole derivatives: spectrum of pharmacological activity and toxicological properties (a review),” Pharmac. Chem. J., 33, No. 5, 232–243 (1999).

    Article  CAS  Google Scholar 

  40. S. Surech, P. K. Blessi, P. Maharaj, et al., “Synthesis of benzimidazole- isatin derivatives for analgesic activity,” Asian Pharmac. Clin. Res., 6, No. 1, 65–67 (2013).

    Google Scholar 

  41. H. Zarrinmayeh, A. M. Nunes, P. L. Ornstein, et al., “Synthesis and evaluation of a series of novel 2-(4-chlorophenoxy)methyl]benzimidazoles as selective neuropeptide YY1 receptor antagonists,” J. Med. Chem., 41, 2709–2719 (1998).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Vernadskii Crimean Federal University, Simferopol, Russia

    I. V. Cheretaev & I. I. Korenyuk

  2. St. Petersburg Sate University, St. Petersburg, Russia

    A. D. Nozdrachev

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  1. I. V. Cheretaev
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  2. I. I. Korenyuk
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  3. A. D. Nozdrachev
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Correspondence to I. V. Cheretaev.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 103, No. 4, pp. 381–390, April, 2017.

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Cheretaev, I.V., Korenyuk, I.I. & Nozdrachev, A.D. Neurotropic, Psychoactive, and Analgesic Properties of Benzimidazole and Its Derivatives: Physiological Mechanisms. Neurosci Behav Physi 48, 848–853 (2018). https://doi.org/10.1007/s11055-018-0639-8

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