Epilepsy and paroxysmal conditions

Advanced search

Study on the antiepyleptic activity of the new amide derivative of valproic acid and 1,3,4-thiadiazole

Full Text:


Aim – experimental evaluation of the antiepileptic activity of a new amide derivative of valproic acid and 1,3,4-thiadiazole.

Materials and Methods: The antiepileptic activity of valprazolamide (N- (5-ethyl-1,3,4-thiadiazol-2-yl) -2-propylpentanamide) was tested in mice using the model of maximal electroshock and also the antagonism model with pentylenetetrazole. Neurotoxicity was assessed with the rotating rod test and the probit analysis. The therapeutic and protective index and the ED50 values were calculated for each experimental model of epilepsy.

Results: The ED50 values of valprazolamide (intraperitoneally) in mice with seizures induced by pentylenetetrazole or maximal electroshock were 74.5 (46.8-106.4) mg/kg or 138.4 (97.2-197.2) mg/kg, respectively.

Conclusion: The new amide derivative of valproic acid and 1,3,4-thiadiazole (valprazolamide) has an antiepileptic activity.

The author declares no financial support or conflict of interest with respect to this publication.

About the Author

A. S. Malygin
Tver State Medical University
Russian Federation
Alexander S. Malygin – MD, Resident-in-Training, Department of Pharmacology & Clinical Pharmacology


1. Freidkova N.V., Pylaeva O.V., Mukhin K.Yu. Valparin XP in the treatment of epilepsy (literature review and description of clinical cases). Russkii zhurnal detskoi nevrologii (in Russ.). 2015; 10 (3): 37-42.

2. Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs. 2012; 16 (10): 695-714.

3. Shnaider N.A., Dmitrenko D.V. Chronic intoxication with valproic acid in epileptology: diagnosis and treatment. Nevrologiya, neiropsikhiatriya, psikhosomatika (in Russ.). 2016; 8 (2): 94-99.

4. Sztajnkrycer M.D. Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol. 2002; 40 (6): 789-801.

5. Jorge Diaz R.A., Enrique Cami Gerardo. Salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole, a structural and analog of acetazolamide, show interesting carbonic anhydrase inhibitory properties, diuretic, and anticonvulsant action. Journal of Enzyme Inhibition and Medicinal Chemistry. 2016; 12 (6): 1102-1111.

6. Trojnar M.K., Wierzchowska-Cioch E., Krzyzanowski M., Jargiełło M., Czuczwar S.J. New generation of valproic acid. Pol J Pharmacol. 2004 May-Jun; 56 (3): 283-8.

7. Patent 2651572 Russian Federation, IPC A 61 K 31/433 N- (5-Ethyl1,3,4-thiadiazol-2-yl) -2-propylpentanamide with antiepileptic and analgesic activities / S.Ya. Skachilova, A.S. Malygin, N.S. Popov et al .; Applicant and patent holder of JSC VSC BAV. No. 267288; declared 03/13/2018; publ. 11/20/2018, Bull. No. 32. 1 p. (in Russ.).

8. Order of the Ministry of Health of the Russian Federation dated 01.04.2016 No. 199n “Rules of Good Laboratory Practice” (in Russ.).

9. Mironov A.N. Guidelines for preclinical studies of drugs. Moscow. 2012; 944 s. (in Russ.).

10. European Convention for the Protection of Vertebrate Animals Used for Experiments or for Other Scientific Purposes (Directive 2010/63 / EU) (in Russ.).

11. Castel-Branco M.M., Alves G.L., Figueiredo I.V., Falcgo A.C.,Caramona M.M. The maximal electroshock seizure (MES) model in the preclinical assessment of potential new antiepileptic drugs. Methods Find Exp Clin Pharmacol. 2009; 31 (2): 101-106.

12. Kandratavicius L., Balista P., Lopes-Aguiar C. et al. Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat. 2014; 10: 1693-1705.

13. Sarma Ph., Bhattacharyya A. Models of epilepsy used in antiepileptic drug discovery: a review. Int J Pharm Pharm Sci. 2014; 6 (11): 1-7.

14. Steven L. Peterson, Timothy E. Albertson. Neuropharmacology methods in epilepsy research. CRC press. 1998; 304 p.

15. Prozorovskii V.B. Statistical processing of the results of pharmacological studies. Psikhofarmakologiya i biologicheskaya narkologiya (in Russ.). 2007; 7 (3-4): 2090-2120.

16. Berezovskaya I.V. Prediction of drug safety in preclinical toxicological studies. Toksikologicheskii vestnik (in Russ.). 2010; 5: 17-22.

17. Dzhagatspanyan I.A., Paronikyan R.G., Nazaryan I.M. Experimental characteristics of the neurotropic spectrum of some antiepileptic drugs. Eksperimental’naya i klinicheskaya farmakologiya (in Russ.). 2003; 66 (6): 20-23.

18. Bertelsen F., Landau A.M., Vase K.H., Jacobsen J. et al. Acute in vivo effect of valproic acid on the GABAergic system in rat brain: A [11C] Ro15-4513 microPET study. Brain Res. 2018 Feb 1; 1680: 110-114.

19. Piplani S., Verma P.K., Kumar A. Neuroinformatics analyses reveal GABAt and SSADH as major proteins involved in anticonvulsant activity of valproic acid. Biomed Pharmacother. 2016; 81: 402-410.

20. Malygin A.S., Popov N.S., Demidova M.A. et al. The effect of valprazolamide on the content of neuroactive amino acids in the brain of rats. Meditsina (in Russ.). 2019; 1: 99-108.


For citations:

Malygin A.S. Study on the antiepyleptic activity of the new amide derivative of valproic acid and 1,3,4-thiadiazole. Epilepsy and paroxysmal conditions. 2019;11(4):357-363. (In Russ.)

Views: 603

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