• BIPUL RAY Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysore, Karnataka, India.
  • KAMSAGARA LINGANNA KRISHNA Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysore, Karnataka, India.


Objectives: The objectives of the present investigation were to evaluate the memory impairment (MI) activity of eslicarbazepine (ESL) in temporal lobe epilepsy (TLE) at a normal and reduced dose, to evaluate the possible protective effect of nefiracetam (NEF) on MI induced by ESL at a normal and reduced dose, and to evaluate the antiepileptic activity of ESL on TLE in the presence and absence of NEF.

Methods: MI activity was evaluated by Barnes maze (BM) on lithium-pilocarpine-induced TLE in Wistar albino rats. Rats were trained by releasing from the portable start-up box after keeping sometimes inside, to find the fixed dark escape hole of BM. Mild aversive light overhead was used to motivate the finding. Animals failed to do so were guided manually. Trained animals were taken for the study and checked the escape latency time (ELT) and the error scores (error entry). The treatment was given for 1 month and MI activity was measured on every 7th day and antiepileptic activity on every 8th day. Phenytoin was used as standard antiepileptic drug (AED) to compare the MI extent of ESL.

Results: ESL-treated group animals had shown increased ELT and error scores, on comparison with control group, implying the MI as a result treatment of the AED ESL. MI was dose dependent and shown decreased MI in animals treated with half dose of ESL. When NEF was administered with the ESL significantly decreased the MI as well as showed potent anticonvulsant activity when compared to control and ESL alone treated group. The levels of acetylcholinesterase (AChE) in ESL group were observed to be increased against control group. Cotreatment of NEF results in decreased levels of AChE on comparison with control and the group treated with ESL.

Conclusion: The reduced dose of ESL and NEF combination was found to have synergized the protecting effect against MI compared to normal ESL and NEF group without altering anticonvulsant activity. However, further studies are required to elicit detailed protective activity of NEF on MI induced by ESL.

Keywords: Eslicarbazepine, Temporal lobe epilepsy, Memory impairment, Lithium-pilocarpine model, Nefiracetam

Author Biography

BIPUL RAY, Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysore, Karnataka, India.

Department of Pharmacology


1. Chizhov AV, Amakhin DV, Zaitsev AV. Computational model of interictal discharges triggered by interneurons. PLoS One 2017;12:e0185752.
2. Lee HF, Chi CS. Febrile infection-related epilepsy syndrome (FIRES): Therapeutic complications, long-term neurological and neuroimaging follow-up. Seizure 2018;56:53-9.
3. Tara E, Vitenzon A, Hess E, Khodakhah K. Aberrant cerebellar Purkinje cell activity as the cause of motor attacks in a mouse model of episodic ataxia Type 2. Dis Model Mech 2018;11:dmm034181.
4. Budikayanti A, Chaliana C, Louisa M, Setiabudy R. Development and validation of carbamazepine plasma concentrations measurement and its application on epilepsy patients. Int J Pharm Pharm Sci 2017;9:87-91.
5. VijayakumarAE,Vinay M, Seethalakshmi.Methanolic extract ofBacopa Monniera reduce developmen of tolerance to antiepileptic effect of phenobarbitone in mice. Int J Pharm Pharm Sci 2015;7:256-9
6. Herzog AG. Catamenial epilepsy: Update on prevalence, pathophysiology and treatment from the findings of the NIH progesterone treatment trial. Seizure 2015;28:18-25.
7. Audrain S, Barnett AJ, McAndrews MP. Language network measures at rest indicate individual differences in naming decline after anterior temporal lobe resection. Hum Brain Mapp 2018;39:4404-19.
8. Stevenson RF, Zheng J, Mnatsakanyan L, Vadera S, Knight RT, Lin JJ, et al. Hippocampal CA1 gamma power predicts the precision of spatial memory judgments. Proc Natl Acad Sci U S A 2018;115:10148-53.
9. Tramoni-Negre E, Lambert I, Bartolomei F, Felician O. Long-term memory deficits in temporal lobe epilepsy. Rev Neurol (Paris) 2017;173:490-7.
10. de Kinderen RJ, Evers SM, Rinkens R, Postulart D, Vader CI, Majoie MH, et al. Side-effects of antiepileptic drugs: The economic burden. Seizure 2014;23:184-90.
11. Curia G, Longo D, Biagini G, Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods 2008;172:143-57.
12. Brandt C, Bankstahl M, Töllner K, Klee R, Löscher W. The pilocarpine model of temporal lobe epilepsy: Marked intrastrain differences in female sprague-Dawley rats and the effect of estrous cycle. Epilepsy Behav 2016;61:141-52.
13. García-García L, Shiha AA, de la Rosa RF, Delgado M, Silván Á, Bascuñana P, et al. Metyrapone prevents brain damage induced by status epilepticus in the rat lithium-pilocarpine model. Neuropharmacology 2017;123:261-73.
14. Lévesque M, Avoli M, Bernard C. Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration. J Neurosci Methods 2016;260:45-52.
15. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 1972;32:281-94.
16. Derera ID, Delisle BP, Smith BN. Functional neuroplasticity in the nucleus tractus solitarius and increased risk of sudden death in mice with acquired temporal lobe epilepsy. eNeuro 2017;4:ENEURO.0319-17.2017.
17. Rosenfeld CS, Ferguson SA. Barnes maze testing strategies with small and large rodent models. J Vis Exp 2014;84:e51194.
18. O’Leary TP, Brown RE. Optimization of apparatus design and behavioral measures for the assessment of visuo-spatial learning and memory of mice on the Barnes maze. Learn Mem 2013;20:85-96.
19. Attar A, Liu T, Chan WT, Hayes J, Nejad M, Lei K, et al. A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer’s disease. PLoS One 2013;8:e80355.
20. Ellman GL, Courtney KD, Andres V Jr., Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-95.
21. Zhao F, Kang H, You L, Rastogi P, Venkatesh D, Chandra M. Neuropsychological deficits in temporal lobe epilepsy: Acomprehensive review. Ann Indian Acad Neurol 2014;17:374-82.
22. Mohan AJ, Krishna KL. Memory impairment allied to temporal lobe epilepsy and its deterioration by phenytoin: Ahighlight on ameliorative effects of levetiracetam in mouse model. Int J Epilepsy 2018;5:19-27.
23. Mula M, Trimble MR. Antiepileptic drug-induced cognitive adverse effects: Potential mechanisms and contributing factors. CNS Drugs 2009;23:121-37.
24. Gawel K, Gibula E, Marszalek-Grabska M, Filarowska J, Kotlinska JH. Assessment of spatial learning and memory in the Barnes maze task in rodents-methodological consideration. Naunyn Schmiedebergs Arch Pharmacol 2019;392:1-18.
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How to Cite
RAY, B., and K. LINGANNA KRISHNA. “ESLICARBAZEPINE AND MEMORY IMPAIRMENT IN TEMPORAL LOBE EPILEPSY: A STUDY ON THE ATTENUATING EFFECT OF NEFIRACETAM”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 2, Dec. 2019, pp. 63-67, doi:10.22159/ajpcr.2020.v13i2.35511.
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