Preview

Epilepsy and paroxysmal conditions

Advanced search

Research and development of 2-ethyl-6-methyl-3-oxypyridine succinate nano-form for the treatment of epilepsy

https://doi.org/10.17749/2077-8333.2018.10.4.026-038

Full Text:

Abstract

The aim is to develop an antiepileptic drug based on polymer nanoparticles with 2-ethyl-6-methyl-3-oxypyridine succinate to facilitate the drug transport through the blood-brain barrier.

Materials and methods. The nano-drug was created using the biologically active substance 2-ethyl-6-methyl-3-hydroxypyridine succinate and polybutyl cyanoacrylate (PBCA) nanoparticles. The advantages of this nano-form over the active ingredient of the same drug were studied using experimental models: the maximum electroshock test (MES), the antagonism test with corazol, models with a cobaltinduced epileptic focus and secondary generalized convulsions, and models of status epilepticus.

Results. The antiseizure effects of the nanoform on the experimental models of epilepsy are identified.

Conclusion. The nano-drug reduces the number of secondary generalized clonic-tonic seizures by 7.8 times; it also reduces 10-fold the animal mortality and diminishes the seizure manifestations that occur in the interictal period of the epileptic status.

About the Authors

G. G. Avakyan
Pirogov Russian National Research Medical University.
Russian Federation

Avakyan Georgii Gagikovich – MD, PhD, Department of Neurology, Neurosurgery and Medical Genetics.

1 Ostrovityanova Str., Moscow 117997.



T. A. Voronina
Zakusov Institute of Pharmacology.
Russian Federation

Voronina Tatyana Aleksandrovna – MD, Professor & Head, Laboratory of Psychopharmacology.

8 Baltijskaja Str., Moscow 125315.



L. N. Nerobkova
Zakusov Institute of Pharmacology.
Russian Federation

Nerobkova Lyubov Nikolaevna – PhD, Senior Research Fellow.

8 Baltijskaja Str., Moscow 125315.



G. N. Avakyan
Pirogov Russian National Research Medical University.
Russian Federation

Avakyan Gagik Norairovich – MD, PhD, Honored Scientist of Russia, Professor at the Department of Neurology, Neurosurgery and Medical Genetics.

1 Ostrovityanova Str., Moscow 117997.


References

1. Kwan P., Brodie M. J. Refractory epilepsy: mechanisms and solutions. Expert Rev Neureuther. 2006; 6 (3): 397-406.

2. Rukosueva N. V. Preparations on the basis of nano particles in clinical practice: achievements and prospects. Voprosy biologicheskoj, medicinskoj i farmacevticheskoj himii. 2014; 2 (4): 19-22 (in Russian).

3. Wagner V., Dullaart A., Bock A. K., Zweck A. The emerging nanomedicine landscape. Nat Biotechnol. 2006; 24 (10): 1211-1217.

4. Voronina T. A. Mexidol: main neuropsychotropic effects and mechanism of action. Farmateka. 2009; 180 (6): 1-4 (in Russian).

5. Voronina T. A., Smirnov L. D., Aliev A. N. et al. The relationship between the chemical structure and the anticonvulsant activity of 3-hydroxypyridine derivatives. Farmakologiya i toksikologiya. 1987; 1: 27-30 (in Russian).

6. Avakyan G. N., Burd S. G., Val’dman E.A., Badalyan O. L., Voronina T. A. Experimental and clinical epileptology: Chapter 8. Epilepsy. S-Pb. 2010; 215-243 (in Russian).

7. Bashkatova V., Narkevich V., Vitskova G. et al. The influence of anticonvulsant and antioxidant drugs on nitric oxide level and lipid peroxidation in the rat brain during penthylenetetrazole-induced epileptiform model seizures. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2003; 27: 487-492.

8. Voronina T. A., Nerobkova L. N. Guidelines for the study of anticonvulsant activity of pharmacological substances. Manual on experimental (preclinical) study of new pharmacological substances. Moscow. 2005; 277-294 (in Russian).

9. Löscher W., Fassbender C. P., Nolting B. The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res. 1991; 8 (2): 79-94.

10. Litchfield J. T., Wilcoxon F. A simplified method of evaluating dose-effect experiments, J. Pharmacol. exp. Ther. 1949; 96: 99; Waud D. R. Analysis of dose-response curves, Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak.P Bd 308, Suppl., S. 1, 1979.

11. Walton N.Y, Jaing Q., Hyun B., Treiman D. M. Lamotrigine vs. phenytoin for treatment of status epilepticus: comparison in an experimental model. Epilepsy Res. 1996; 24 (1): 19-28.

12. Alyautdin R. N., Dzhindzhihashvili I. A., Kurahmaeva K. B., Balabanyan V. Yu., Petrov V. E., Voronina T. A. Directed transport of drugs to the brain with nanotransport system. Molekulyarnayamedicina. 2008; 3: 17-24.

13. Gulyaev A. E., Gelperina S. E., Skidan I. N., Antropov A. S., Kivman G. Y., Kreuter J. Significant trапsроrt of doxorubicin into the brаiп with polysorbate 80-coated nanoparticles, Рhаrm. Res. 1999; 16: 15б4-15б9.

14. Behan N., Birkinshaw С., Clarke N. Poly n-butyl cyanoacrylate nanoparticles: а mechanistic: study of polymerisation and particle formаtiоn. Biomaterials. 2001 Jun; 22 (11): 1335-44.

15. Vаuthiеr С., Dubernet С., Fattal E., Pinto-Аlрhапdаrу Н., Couvreur Р. Poly.(alkylcyanoacrylates) as biodegradable materials for biomedical applications. Adv Drug Deliv Rev. 2003 Арr 25; 55(а): 519-48.

16. Voronina T. A., Kurahmaeva K. B., Razzhivina V. A., Dzhindzhihashvili I. A., Balabanyan V. Yu., Nerobkova L. N., Avakyan G. G. Perspectives of creation neuropsychotropic drags with nanotechnology. Materialy IV sezda-farmakologov Rossii. 18-21 sentyabrya 2012 g. Kazan. Rossia. 2012. s. 40.


Review

For citations:


Avakyan G.G., Voronina T.A., Nerobkova L.N., Avakyan G.N. Research and development of 2-ethyl-6-methyl-3-oxypyridine succinate nano-form for the treatment of epilepsy. Epilepsy and paroxysmal conditions. 2018;10(4):26-38. (In Russ.) https://doi.org/10.17749/2077-8333.2018.10.4.026-038

Views: 640


ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)