Neuroscience and Behavioral Physiology

, Volume 49, Issue 9, pp 1127–1134 | Cite as

Modulation of Nicotinic Receptors in Neurons in the Common Snail by Noopept and Piracetam

  • M. A. Razumovskaya
  • G. B. Murzina
  • R. U. Ostrovksaya
  • A. S. PivovarovEmail author

The nootropic agents noopept and piracetam alter the amplitudes of acetylcholine-induced influx currents (ACh currents) in command neurons in the common snail. Both compounds have cholinopositive activity. The dose curve of the actions of noopept is bell-shaped, while the piracetam dose-response curve in the range of physiological concentrations shows a monotonous rise. Noopept increases the ACh current at low concentrations (10–10–10–8 M), while piracetam acts at significantly higher concentrations (starting from 10–4 M). The magnitudes of the maximal cholinopositive effects of noopept and piracetam (in the range of physiological concentrations) were identical, while the concentrations of nootropic drugs at which they were reached differed by seven orders of magnitude. The half-maximal concentration (EC50) of noopept was 10–10 M and that of piracetam was 10–3 M. The mechanisms of the cholinopositive actions of these drugs are discussed.


acetylcholine noopept piracetam dose–effect relationships 


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  1. Bering, B. and Müller, W. E., “Interaction of piracetam with several neurotransmitter receptors in the central nervous system,” Drug Res., 35, 1350–1352 (1985).Google Scholar
  2. Boiko, S. S., Korotkov, S. A., Zherdev, V. P., et al., “Pharmacokinetics and BBB permeability of a novel acylprolinedipeptide with nootropic properties after oral administration,” Byull. Eksperim. Biol. Med., 129, No. 4, 426–429 (2000).Google Scholar
  3. Bulatov, V. V., Khokhoev, T. Kh., Dikii, V. V., et al., “The problems of small and supersmall doses in toxicology. Basic and applied aspects,” Ros Khim. Zh., XLVI, No. 6, 58–62 (2002).Google Scholar
  4. Calabrese, E. J., Iavicoli, I., and Calabrese, V., “Hormesis: its impact on medicine and health,” Hum. Exp. Toxicol., 32, No. 2, 120–52 (2013), doi: Scholar
  5. Collerton, F., “Cholinergic function and intellectual decline in Alzheimer’s disease,” Neuroscience, 19, l–28 (1986).CrossRefGoogle Scholar
  6. Everitt, B. J. and Robbins, T. W., “Central cholinergic systems and cognition,” Annu. Rev. Psychol., 48, 649–684 (1997).CrossRefGoogle Scholar
  7. Froestl, W., Muhs, A., and Pfeifer, A., “Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors,” J. Alzheimers Dis., 32, No. 4, 793–887 (2012), doi: Scholar
  8. Gudasheva, T. A. and Skoldinov, A. P., “A strategy for creating dipeptide neuropsychotropic drugs,” Eksperim. Klin. Farmakol., 66, No. 2, 15–19 (2003).Google Scholar
  9. Gudasheva, T. A., “A strategy for the creation of dipeptide drugs,” Vestn. Ross. Akad. Med. Nauk., 7, 8–16 (2011).Google Scholar
  10. Gudasheva, T. A., Voronina, T. A., Ostrovskaya, R. U., et al., “Synthesisand antiamnestic activity of a series of N-acylprolyl-containing dipeptides,” Eur. J. Med. Chem., 31, No. 2, 151–157 (1996).CrossRefGoogle Scholar
  11. Hernandez, C. M. and Dineley, K. T., “α7 Nicotinic acetylcholine receptors in Alzheimer’s disease: neuroprotective, neurotrophic or both?” Curr. Drug Targ., 13, No. 5, 613–622 (2012).CrossRefGoogle Scholar
  12. Ierusalimskii, V. N., Zakharov, I. S., Palikhova, T. A., and Balaban, P. M., “The nervous system and neuron mapping in the gastropod mollusk Helix lucorum, L.,” Zh. Vyssh. Nerv. Deyat., 42, No. 6, 1075–1089 (1992).Google Scholar
  13. Leuner, K., Kurz, Ch., Guidetti, G., et al., “Improved mitochondrial function in brain aging and Alzheimer disease -the new mechanism of action of the old metabolic enhancer piracetam,” Front. Neurosci., 4, Art. 44 (2010), doi 10.3389/fnins.2010.00044.Google Scholar
  14. Lombardo, S. and Maskos, U., “Role of the nicotinic acetylcholine receptor in Alzheimer’s disease pathology and treatment,” Neuropharmacology, 96, part B, 255–262 (2015), doi
  15. Malykh, A. G. and Reza Sadaie, M., “Piracetam and piracetam-like drugs. From basic science to novel clinical applications to CNS disorders,” Drugs, 70, No. 3, 287–312 (2010).CrossRefGoogle Scholar
  16. Müller, W. E., Koch, S., Scheuer, K., et al., “Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain,” Biochem. Pharmacol., 53, No. 2, 135–140 (1997).CrossRefGoogle Scholar
  17. Murzina, G. B., “The effects of lateral diffusion of receptors on depression of neuron cholinosensitivity,” Biofizika, 58, No. 3, 516–523 (2013).Google Scholar
  18. Ostrovskaya, R. U., Gudasheva, T. A., Voronina, T. A., and Seredenin, S. B., “The original nootropic and neuroprotective drug noopept (GVS-111),” Eksp. Farm. Toksikol., 5, 66–73 (2002).Google Scholar
  19. Ostrovskaya, R. U., Mirzoev, T. Kh., Firova, F. A., et al., “Behavioral and electrophysiological analysis of the cholinopositive action of the nootropic acylproline dipeptide GVS-111,” Eksp. Klinich. Farmakol., 64, No. 2, 11–14 (2001).Google Scholar
  20. Ostrovskaya, R. U., Tsaplina, A. P., Vakhitova, Yu. V., et al., “Efficacy of the nootropic and neuroprotective dipeptide noopept in a streptozotocin model of Alzheimer’s disease in rats,” Eksp. Klinich. Farmakol., 73, No. 12, 2–5 (2010).Google Scholar
  21. Ostrovskaya, R. U., Vahitova, J. V., Salimgareeva, M. H., et al., “Noopept stimulates the expression of NGF and BDNF in rat hippocampus,” Bull. Exp. Biol. Med., 14, No. 2, 334–337 (2008).CrossRefGoogle Scholar
  22. Ostrovskaya, R. U., Vakhitova, Y. V., Kuzmina, U. Sh., et al., “Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation,” J. Biomed. Sci., 6, No. 21, 74 (2014), doi: 10.1186/s12929-014-0074-2.Google Scholar
  23. Pelsman, A., Hoyo-Vadillo, C., Gudasheva, T. A., et al., “GVS-111 prevents oxidative damage and apoptosis in normal and Down’s syndrome human cortical neurons,” Int. J. Dev. Neurosci., 21, No. 3, 117–124 (2003).CrossRefGoogle Scholar
  24. Pepeu, G. and Spignoli, G., “Nootropic drugs and brain cholinergic mechanisms,” Prog. Neuropsychopharmacol. Biol. Psychiatry, 13, Supplement, S77–S88 (1989).Google Scholar
  25. Peuvot, J., Schanck, A., Deleers, M., and Brasseur, R., “Piracetam-induced changes to membrane physical properties. A combined approach by 31P nuclear magnetic resonance and conformational analysis,” Biochem. Pharmacol., 50, No. 8, 1129–1134 (1995).CrossRefGoogle Scholar
  26. Pilch, H. and Müller, W. E., “Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice,” Psychopharmacology, 9, No. 4, 74–78 (1988).Google Scholar
  27. Pivovarov, A. S. and Drozdova, E. I., “Identification of cholinoreceptors on the bodies of RPa3 and LPa3 neurons in the common snail,” Neirofiziologiya, 24, No. 1, 77–86 (1992).Google Scholar
  28. Pivovarov, A. S., “Cholinoreceptors of neurons in the common snail: identification, plasticity, and its regulation by opioids and second messengers,” Zh. Vyssh. Nerv. Deyat., 42, No. 6, 1271–1286 (1992).Google Scholar
  29. Pivovarov, A. S., Ostrovskaya, R. U., Drozdova, E. I., and Saakyan, S. A., “The effects of piracetam on acclimation of the cholinoreceptor membrane in the common snail,” Byull. Eksperim. Biol. Med., 104, No. 7, 51–53 (1987).Google Scholar
  30. Pugsley, T. A., Shih, Y. H., Coughenoor, L., and Stewart, S. F., “Some neurochemical properties of pramiracetam (CI-879), a new cognition enhancing agent,” Drug Dev. Res., 2, 407–420 (1983).CrossRefGoogle Scholar
  31. Radionova, K. S., Bel’nik, A. P., and Ostrovskaya, R. U., “The original nootropic drug ‘Noopept’ eliminates memory defects induced by blockade of muscarinic and nicotinic cholinoreceptors in rats,” Byull. Eksperim. Biol. Med., 146, No. 7, 65–68 (2008).Google Scholar
  32. Sakurai, T., Kato, T., Mori, K., et al., “Nefiracetam elevates extracellular acetylcholine level in the frontal cortex of rats with cerebral cholinergic dysfunctions: an in vivo microdialysis study,” Neurosci. Lett., 246, No. 2, 69–72 (1998).CrossRefGoogle Scholar
  33. Scheuer, K., Rostock, A., Bartsch, R., and Müller, W. E., “Piracetam improves cognitive performance by restoring neurochemical deficits of the aged rat brain,” Pharmacopsychiatry, 32, Suppl. 1, 10–16 (1999).CrossRefGoogle Scholar
  34. Solntseva, E. I., Bukanova, J. V., Ostrovskaya, R. U., et al., “The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels,” Gen. Pharmacol., 29, No. 1, 85–89 (1997).CrossRefGoogle Scholar
  35. Winblad, B., “Piracetam: a review of pharmacological properties and clinical uses,” CNS Drug Rev., 11, No. 2, 169–182 (2005).CrossRefGoogle Scholar
  36. Zhao, X., Kuryatov, A., Lindstrom, J. M., et al., “Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons,” Mol. Pharmacol., 59, No. 4, 674–683 (2001).CrossRefGoogle Scholar
  37. Zherdev, V. P., Boiko, S. S., Neznamov, G. G., et al., “Clinical pharmacokinetics of noopept in patients with intellectual-mnestic disorders,” Klinich. Farmakokin., 2, No. 2, 49–52 (2005).Google Scholar

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Authors and Affiliations

  • M. A. Razumovskaya
    • 1
  • G. B. Murzina
    • 2
  • R. U. Ostrovksaya
    • 3
  • A. S. Pivovarov
    • 1
    Email author
  1. 1.Department of Higher Nervous ActivityLomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute of Higher Nervous Activity and NeurophysiologyRussian Academy of SciencesMoscowRussia
  3. 3.Zakusov Research Institute of PharmacologyMoscowRussia

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