Skip to main content

Advertisement

Log in

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

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bering, B. and Müller, W. E., “Interaction of piracetam with several neurotransmitter receptors in the central nervous system,” Drug Res., 35, 1350–1352 (1985).

    CAS  Google Scholar 

  • 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 

  • 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).

  • 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: https://doi.org/10.1177/0960327112455069.

    Article  CAS  Google Scholar 

  • Collerton, F., “Cholinergic function and intellectual decline in Alzheimer’s disease,” Neuroscience, 19, l–28 (1986).

    Article  CAS  Google Scholar 

  • Everitt, B. J. and Robbins, T. W., “Central cholinergic systems and cognition,” Annu. Rev. Psychol., 48, 649–684 (1997).

    Article  CAS  Google Scholar 

  • 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: https://doi.org/10.3233/JAD-2012-121186.

    Article  CAS  PubMed  Google Scholar 

  • Gudasheva, T. A. and Skoldinov, A. P., “A strategy for creating dipeptide neuropsychotropic drugs,” Eksperim. Klin. Farmakol., 66, No. 2, 15–19 (2003).

    CAS  Google Scholar 

  • Gudasheva, T. A., “A strategy for the creation of dipeptide drugs,” Vestn. Ross. Akad. Med. Nauk., 7, 8–16 (2011).

    Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • 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.

  • 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 https://doi.org/10.1016/j.neuropharm.

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  Google Scholar 

  • Murzina, G. B., “The effects of lateral diffusion of receptors on depression of neuron cholinosensitivity,” Biofizika, 58, No. 3, 516–523 (2013).

  • 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 

  • 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).

    CAS  Google Scholar 

  • 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 

  • 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).

    Article  Google Scholar 

  • 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.

  • 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).

    Article  CAS  Google Scholar 

  • Pepeu, G. and Spignoli, G., “Nootropic drugs and brain cholinergic mechanisms,” Prog. Neuropsychopharmacol. Biol. Psychiatry, 13, Supplement, S77–S88 (1989).

  • 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).

    Article  CAS  Google Scholar 

  • 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).

  • 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).

  • 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).

    CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • 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).

    Article  Google Scholar 

  • 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 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • Winblad, B., “Piracetam: a review of pharmacological properties and clinical uses,” CNS Drug Rev., 11, No. 2, 169–182 (2005).

    Article  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. S. Pivovarov.

Additional information

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 68, No. 4, pp. 537–548, July–August, 2018.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Razumovskaya, M.A., Murzina, G.B., Ostrovksaya, R.U. et al. Modulation of Nicotinic Receptors in Neurons in the Common Snail by Noopept and Piracetam. Neurosci Behav Physi 49, 1127–1134 (2019). https://doi.org/10.1007/s11055-019-00849-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-019-00849-2

Keywords

Navigation