Skip to main content
Log in

Stimulation of Gastric Mucosal Afferents with Mesaton Potentiates the Anticonvulsant and Eliminates the Sedative Actions of Sodium Valproate in Rats with Corasol Kindling

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

Chronic oral sodium valproate given at high doses (100–200 mg/kg) suppressed the development of generalized clonic-tonic corasol (pentylenetetrazole) kindled convulsions in 100% of rats but prevented local clonic kindled convulsions in only 33–57%. At these doses, sodium valproate induced strong sedation. Combined chronic oral administration of Mesaton at the threshold dose of 0.2 mg/kg, inactive when give alone, and sodium valproate at the high doses of 100 and 200 mg/kg potentiated the anticonvulsant action of sodium valproate and prevented not only clonic-tonic kindled convulsions in 100% of rats, but also clonic kindled convulsions in 86–100% of rats, and also increased the anticonvulsant activity of valproate by factors of 1.7–1.9. These combinations of sodium valproate with Mesaton did not induce any sedative side effect. The mechanism of potentiation of the anticonvulsant effect and elimination of the sedative side effect of high-dose sodium valproate is based on stimulation of gastric mucosal afferents by Mesaton.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

  1. S. E. Serdyuk and V. E. Gmiro, “Stimulation of gastric mucosal afferents by adrenaline potentiates the anticonvulsant but not the sedative action of diazepam in rats,” Ross. Fiziol. Zh., Vol. 98, No. 2, 236–241 (2012).

    CAS  Google Scholar 

  2. C. L. Deckers, Y. A. Hekster, A. Keyser, et al., “Adverse effects in epilepsy therapy. Wait and see or go for it?” Acta Neurol. Scand., 95, No. 4, 248–252 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. W. Fischer and H. Kittner, “Influence of ethanol on the pentylenetetrazol-induced kindling in rats,” Neural Transm., 105, No. 10–12, 1129–1142 (1998).

    Article  CAS  Google Scholar 

  4. R. N. Hughes, “Effects on open-field behavior of diazepam and buspirone alone and in combination with chronic caffeine,” Life Sci., 53, No. 15, 1217–1225 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. G. M. Kennedy and S. D. Lhatoo, “CNS adverse events associated with antiepileptic drugs,” CNS Drugs, 22, No. 9, 739–760 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. W. Loscher, “Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action,” Progr. Neurobiol., 58, No. 1, 31–59 (1999).

    Article  CAS  Google Scholar 

  7. W. Loscher and I.E. Leppik, “Critical re-evaluation of previous preclinical strategies for the discovery and the development of new antiepileptic drugs,” Epilepsy Res., 50, No. 1–2, 17–20 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. J. Mehla, K. H. Reeta, P. Gupta, and Y. K. Gupta, “Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model,” Life Sci., 87, No. 19–22, 596–603 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. K. Morimoto, M. Fahnestock, and R. J. Racine, “Kindling and status epilepticus models of epilepsy: rewiring the brain,” Progr. Neurobiol., 73, No. 1, 1–60 (2004).

    Article  CAS  Google Scholar 

  10. O. Miyamoto, J. Pang, K. Sumitani, et al., “Mechanisms of the anti-ischemic effect of vagus nerve stimulation in the gerbil hippocampus,” Neuroreport, 14, No. 15, 1971–1974 (2003).

    Article  PubMed  Google Scholar 

  11. Y. Ohno, S. Ishihara, R. Terada, et al., “Anti-epileptogenic and anticonvulsant actions of levetiracetam in a pentylenetetrazole kindling model,” Epilepsy Res., 89, No. 2–3, 360–364 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. K. Otsuki, K. Morimoto, K. Sato, et al., “Effects of lamotrigine and conventional antiepileptic drugs on amygdala- and hippocampal-kindled seizures in rats,” Epilepsy Res., 31, No. 2, 101–112 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. E. Perucca, A. Aldenkamp, R. Tanis, and G. Krämer, “Role of valproate across the ages. Treatment of epilepsy in the elderly,” Acta. Neurol. Scand., Supplement, 184, 28–37 (2006).

  14. S. Rao, K. R. Rajesh, and T. Joseph, “Effect of antiepileptic drugs valproic acid carbamazepine and ethosuccimide on exploratory behaviour in mice,” Indian Exp. Biol., 29, No. 2, 127–130 (1991).

    CAS  Google Scholar 

  15. G. Roks, C. L. Deckers, H. Meinardi, et al., “Effects of polytherapy compared with monotherapy in antiepileptic drugs: an animal study,” Pharmacol. Exp. Ther., 288, No. 2, 472–477 (1999).

    CAS  Google Scholar 

  16. P. A. Rutecki and B. E. Gidal, “Antiepileptic drug treatment in the developmentally disabled: treatment considerations with the newer antiepileptic drugs,” Epilepsy Behav., 3, No. 6S1, 24–31 (2002).

    Article  PubMed  Google Scholar 

  17. R. Talati, J. M. Scholle, O. P., Phung, et al., “Efficacy and safety of innovator versus generic drugs in patients with epilepsy: a systematic review,” Pharmacotherapy, 32, No. 4, 314–322 (2012).

    Article  CAS  PubMed  Google Scholar 

  18. P. Tirassa, N. Costa, and L. Aloe, “CCK-8 prevents the development of kindling and regulates the GABA and NPY expression in the hippocampus of pentylenetetrazole (PTZ)-treated adult rats,” Neuropharmacology, 48, No. 5, 732–742 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. H. C. Tomasiewicz, S. D. Mague, B. M. Cohen, and W. A. Carlezon, “Behavioral effects of short-term administration of lithium and valproic acid in rats,” Brain. Res., 1093, No. 1, 83–94 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. R. D. Whitlow, A. Sacher, D. D. Loo, et al., “The anticonvulsant valproate increases the turnover rate of gamma-aminobutyric acid transporters,” J. Biol. Chem., 278, No. 20, 17,716–17,726 (2003).

    Article  CAS  Google Scholar 

  21. X. H. Wu, M. P. Ding, Z. Zhu-Ge, et al., “Carnosine, a precursor of histidine ameliorates pentylenetetrazole-induced kindled seizures in rat,” Neurosci. Lett., 400, No. 1–2, 146–149 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. E. Gmiro.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 100, No. 1, pp. 96–104, January, 2014.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Serdyuk, S.E., Gmiro, V.E. & Veselkina, O.S. Stimulation of Gastric Mucosal Afferents with Mesaton Potentiates the Anticonvulsant and Eliminates the Sedative Actions of Sodium Valproate in Rats with Corasol Kindling. Neurosci Behav Physi 45, 795–799 (2015). https://doi.org/10.1007/s11055-015-0146-0

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-015-0146-0

Keywords

Navigation