COMPARATIVE ANTICONVULSANT AND ANTIHYPOXIC EFFECTS OF ASTROKS AND MEXIDOL IN INJECTABLE FORM AND 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE SUCCINATE SUBSTANCE
Abstract
The purpose of this study was to examine in experiment anticonvulsant and antihypoxic action of 2-ethyl-6-methyl-3-hydroxypyridine succinate medications — Astroks in injectable form (vial of 100 mg in 2 ml) compared with Mexidol injectable form (vial of 100 mg in 2 ml) and the substance 2-ethyl-6- methyl-3-hydroxypyridine succinate (EMHPS).
Materials and methods. Simulation of primary generalized eizures was performed using the maximal electroshock (MES) and pentylenetetrazole injection. Antihypoxic effects of drugs was studied on the model of normobaric hypoxia with hypercapnia.
Results: it was found that astroks injection at a dose of 200 mg/kg has a similar antihypoxic and anticonvulsant efficacy with EMHPS substance. Compared to injectable form of Meksidol astroks has similar efficacy in the test of antagonism with MES. Astroks exceeds the effect of Mexidol in the test of antagonism with pentylenetetrazole and has more severe antihypoxic action.
Conclusion. Аstroks injectable has pronounced antihypoxic and anticonvulsant action in the experiment which have some advantages over injectable Meksidol.
About the Authors
T. A. Voronina
Institute of Pharmacology named V. V. Zakusov, Moscow
Russian Federation
Russian Federation
professor, MD, head of the Laboratory of Psychopharmacology Institute of Pharmacology named V. V. Zakusov RAS. Address: ul. Baltiiskaya, 8, 125315, Moscow, Russia. Tel.: +7(495)6012414
S. A. Litvinova
Institute of Pharmacology named V. V. Zakusov, Moscow
Russian Federation
Russian Federation
Ph.D., Leading Research Fellow, Institute of Pharmacology named V. V. Zakusov RAS. Address: ul. Baltiiskaya, 8, Moscow, Russia, 125315. Tel.: +7(495)6012414
L. N. Nerobkova
Institute of Pharmacology named V. V. Zakusov, Moscow
Russian Federation
Russian Federation
Ph.D., Senior Research Fellow, Institute of Pharmacology named V. V. Zakusov RAS. Address: ul. Baltiiskaya, 8, Moscow, Russia, 125315. Tel.: +7(495)6012414
G. G. Avakyan
The Russian National Research Medical University named after N. I. Pirogov of the Ministry of Health of the Russian Federation, Moscow
Russian Federation
Russian Federation
MD, PhD, Department of Neurology, Neurosurgery and Medical Genetics, Medical University RNIMU them NI Pirogov. Address: ul. Ostrovityanova, 1, Moscow, Russia, 117997. Tel.: 79151879506.
I. O. Gaidukov
Institute of Pharmacology named V. V. Zakusov, Moscow
Russian Federation
Russian Federation
Junior Research Fellow, Institute of Pharmacology named V. V. Zakusov RAS. Address: ul. Baltiiskaya, 8, Moscow, Russia, 125315. Tel.: +7(495)6012414
G. N. Avakyan
The Russian National Research Medical University named after N. I. Pirogov of the Ministry of Health of the Russian Federation, Moscow
Russian Federation
Russian Federation
MD, Honored Scientist of Russia, Professor of Neurology and Neurosurgery, Medical University RNIMU them NI Pirogov. Address: ul. Ostrovityanova, 1, Moscow, Russia, 117997
References
1. Avakian G. G., Nerobkova L. N., Oleynikov O. M., Voronina T. A., Avakian G. N.,
2. Gusev E. I. Possible applications of valproate and antioxidant with secondary generalized seizures (clinical and experimental study) (in Russian). Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions. 2011; 3: 2: 34-44.
3. Aliyev A. N. Characteristics of anticonvulsant activity in a series of 3-hydroxypyridine (head — T. A. Voronina) (in Russian): Abstract. Dis. Ph.D. Baku. 1987; 21.
4. Badalyan O. L., Avakian G. N., Voronina T. A., Nerobkova L. N. The possibility of using a combination of carbamazepine and mexidolum adolescents. Proceedings of the II East European Conference Epilepsy and Clinical Neurophysiology (in Russian). Gurzuf 2000; 260-262.
5. Voronina T. A., Smirnov L. D., Aliyev A. N., Kuzmin E. I., Tilekeeva U.M, Ahmedov E. F., Dumas K. M. The relationship between the chemical structure and anticonvulsant activity of 3-hydroxypyridine (in Russian). Pharmacol and Toxicology. 1987; 1: 27-30.
6. Voronina T. A., Nerobkova L. N., Markina N. V., Taranov N. P., Aliyev A. L., Sokolov N. E., Nilov N. S. Possible mechanisms of action of membrane-active substances with antioxidant properties in extreme situations. Cellular mechanisms of
7. implementation pharmacological effect (in Russian). Moscow. 1990; 54-77.
8. Voronina T. A. Mexidol. Main neuropsychotropic effects and mechanism of action (in Russian). Pharmateka. 2009; 180: 6: 1-4.
9. Voronina T. A., Nerobkova L. N. Methodological recommendations for Preclinical Study of the anticonvulsant activity of the drugs. Guidelines for conducting pre-clinical trials of medicinal products (in Russian) Part 1, Chapter 14. FGBU “NCESMP “ Health Ministry of Russia. Moscow. 2012; 235-250.
10. Voronina T. A., Ostrovskaya R. U., Garibov T. L. Guidelines for pre-clinical study of drugs with neuroprotective action type. Guidelines for conducting pre-clinical trials of medicinal products (in Russian). Part 1. Chapter 17. Edition: FGBU “NCESMP” Health Ministry of Russia. Moscow. 2012; 276-296.
11. Voronina T. A. Mexidol: spectrum of pharmacological effects (in Russian). Journal neur and psych. 2012; 12: 86-90.
12. Gaeva M. D., Pogorelyi V. E., Arlt A. V. Anti-ischemic protection of the brain antioxidant group 3-hydroxypyridine. New trends of drug development (in Russian). Congress Man and Medicine. 1997; 52.
13. Dumas K. M., Voronina T. A., Smirnov L. D. Patent. Nootropics (in Russian). №1761146, 1985.
14. Dumas K. M., Voronina T. A., Smirnov L. D. Antioxidants in prophylaxis and therapy of CNS pathologies (in Russian). Moscow. 1995; 271.
15. Eremenko A. V. Role membranotropic properties of 3-hydroxypyridine in the pharmacological effect (in Russian). Abstract. diss. Ph.D. Moscow. 1988; 22.
16. Lukyanova L. D., Atabaeva R. E., Shepeleva S. Y. Bioenergy mechanisms antihypoxic action succinate containing a 3-hydroxypyridine (in Russian). Bull Experiment biol and med. 1993; 3: 259-260.
17. Nerobkova L. N., Voronina T. A., Aliyev A. N., Smirnov L. D., Kryzhanovsky G. N., Braslavsky V. E., Nikushkin E. V. On the electrophysiological and biochemical mechanisms of anticonvulsant action of antioxidant from the class of 3-hydroxypyridine (in Russian). Bull Experiment biol and med. 1986; 12: 663-665.
18. Novikov V. E., Kulagin K. N., Kovaleva L. A. Activity of lipid peroxidation in the dynamics of traumatic brain injury and its correction meksidolum. Proceedings of
19. he 4th scientific-practical conference with international participation. Reactive oxygen species, nitric oxide, antioxidants and human health (in Russian). Smolensk, 2005; 283-284.
20. Seredenin S. B., Blednov Y. A., Gordey M. L., Voronina T. A., Smirnov L. D. Influence membrane — modulatory 3-hydroxypyridine in the emotional stress response and linking H3- diazepam in the brain of inbred mice (in Russian). Chemical and pharmaceutical J. 1987; 2: 134-137.
21. Smirnov L. D., Voronina T. A., Dumas K. M., Rudenko G. M., Morozov G. V. Patent. Anti-alcohol agent (in Russian). №1777878.1984.
22. Smirnov L. D., Voronina T. A. Patent. The medicament for the treatment of drug
23. addiction (in Russian). №2159615. 1999.
24. Smirnov L. D., Voronina T. A. Patent. Cerebroprotective medicament (in Russian). № 2145855, 1989.
25. Stojko M. I. Explore the possibility of the use of sodium valproate, and their antioxidant mexidolum and combinations thereof for the treatment and prevention of secondary generalized seizures in epilepsy (head — T. A. Voronina) (in Russian): Abstract. Dis. Ph.D. Moscow. 2002; 23.
26. Tilekeeva U. M. The psychotropic properties of 3-hydroxypyridine (head — TA Voronina) (in Russian): Abstract. Dis. Ph.D. Moscow. 1986; 20.
27. Shulkina A. V. Mexidol Influence on the development of the phenomenon of excitotoxicity in vitro neurons (in Russian). Journal Neurology and Psychiatry. 2012; 2: 35-39.
28. Yasnetsov V. V. Influence of some neurotropic substances on mitochondrial respiration of brain cells in rats (in Russian). Bulletin VolGMU. 2009; 2: 72-73.
29. Yasnetsov V. V., Voronina T. A. Action semax and mexidol model of cerebral ischemia in rats (in Russian). Experiment and wedge Pharmacology. 2009; 22: 1: 68-70.
30. Bashkatova V., Narkevich V., Vitskova G., Vanin A. The influence of anticonvulsant and antioxidant drugs on nitric oxide level and lipid peroxidation in the rat brain during penthylenetetrazole-induced epileptiform model seizures (in Russian). Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27: 487-492.
31. European Medicines Agency (EMEA), Committee for Proprietary Medicinal Products (CPMP), Note for guidance on the investigation of bioavailability and bioequivalence. CPMP/EWP/QWP/1401/98, 2001 July.
32. Food and Drug Administration (FDA), U. S. Center for Drug Evaluation and Research (CDER), Guidance for industry: Bioavailability and bioequivalence studies for orally administered drug products — general considerations. Washington. 2003.
33. Pitkдnen А., Schwartzkroin P. A., Moshй S. L. Models of Seizures and Epilepsy, Academic Press. 2005; 712.
34. Voronina T. A., Seredenin S. B. Analysis of the mechanism of psychotropic action of 3-hydroxypyridine derivative. Ann Ist Super Sanita. 1988; 24: 461-466.
35. Voronina T. A. Present-day problems in experimental psychopharmacology of nootropic drugs. Neuropharmacology. Harwood Academic Publishers GmbH U.K. 1992; 2: 51-108.
36. Voronina T. A. Nootropic drugs in Alzheimer disease treatment. New Pharmacological Strategies. In book: Alzheimer disease: therapeutic strategies. Birkhauser. Boston. 1994; 265-269.
For citation:
Voronina T.A., Litvinova S.A., Nerobkova L.N., Avakyan G.G., Gaidukov I.O., Avakyan G.N. COMPARATIVE ANTICONVULSANT AND ANTIHYPOXIC EFFECTS OF ASTROKS AND MEXIDOL IN INJECTABLE FORM AND 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE SUCCINATE SUBSTANCE. Epilepsia and paroxysmal conditions. 2016;8(1):75-82. (In Russ.) https://doi.org/10.17749/2077-8333.2016.8.1.075-082
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