Antiepileptic drugs: newer targets and new drugs

Vihang S. Chawan, Abhishek M. Phatak, Kalpesh V. Gawand, Sagar V. Badwane, Sagar S. Panchal


Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs), but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and drug administration (USFDA) has approved eslicarbazepine acetate, ezogabine, perampanel and brivaracetam which have shown a promising future as better AEDs and drugs like ganaxolone, intranasal diazepam, ICA- 105665, valnoctamide, VX-765, naluzotan are in the pipeline.


Epilepsy, Newer antiepileptic drugs, Eslicarbazepine Acetate, Ezogabine (Retigabine), Perampanel, Brivaracetam, Naluzotan

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Mcnamara JO. Pharmacotherapy of the epilepsies. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gillman’s The Pharmacological Basis of Therapeutics. 12th edition. New York, NY, McGraw Hill;2011:583-607.

Indian Epilepsy Association-18th International epilepsy congress trust. 2008. Available at Accessed on 3 March 2016.

Chung SS, Kelly K, Schusse C. New and emerging treatments for epilepsy: review of clinical studies of lacosamide, eslicarbazepine acetate, ezogabine, rufinamide, perampanel, and electrical stimulation therapy. Journal of Epilepsy Research. 2011;1(2):35-46.

Lee SK. Old versus new: why do we need new antiepileptic drugs? Journal of Epilepsy Research. 2014;4(2):39-44.

Chu SCJ, Thiele EA. New drugs for pediatric epilepsy. Semin Pediatr Neurol. 2010;7(4):214-23.

Fattore C, Perucca E. Novel medications for epilepsy. Drugs. 2011;71(16):2151-78.

Verrotti A, Loiacono G, Rossi A, Zaccara G. Eslicarbazepine acetate: an update on efficacy and safety in epilepsy. Epilepsy Res. 2014;108(1):1-10.

Almeida L, Silva SP. Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics. 2007;4:88-96.

Bonifacio MJ, Sheridan RD, Parada A, Cunha RA, Patmore L, Silva SP. Interaction of the novel anticonvulsant, BIA 2-093, with voltage-gated sodium channels: comparison with carbamazepine. Epilepsia. 2001;42:600-8.

Zaccara G, Giovannelli F, Cincotta M, Carelli A, Verrotti A. Clinical utility of eslicarbazepine: current evidence. Drug Des Devel Ther. 2015;9:781-9.

Riss J, Cloyd J, Gates J, Collins S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008;118(2):69-86.

Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G. In-vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004;32(11):1279-86.

Contin M, Sangiorgi S, Riva R, Parmeggiani A, Abani F, Baruzzi A. Evidence of polymorphic CYP2C19 involvement in the human metabolism of n-desmethylclobazam. Ther Drug Monit. 2002;24(6):737-41.

Silveira MR, Mentenegro MA, Franzon RC, Guerreiro CA, Geurreiro MM. Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy. Arq Neuropsiquiatr. 2006;64(3B):705-10.

Chiron C, Dulac O. The pharmacologic treatment of Dravet syndrome. Epilepsia. 2011;52(2):72-5.

Johannessen SI, Landmark CJ. antiepileptic drug interactions - principles and clinical implications. Current Neuropharmacology. 2010;8(3):254-67.

Aneja S, Sharma S. Newer Antiepileptics. Indian Pediatr. 2013;50:1033-40.

Willmore LJ. Losigamone. Dr Willmar Schwabe. Curr Opin Investig Drugs. 2001;2(12):1763-6.

Xiao Y, Luo M, Wang J, Luo H. Losigamone add-on therapy for partial epilepsy. Cochrane Database Syst Rev. 2015;12:CD009324.

Reddy DS, Rogawski MA. Neurosteroids endogenous regulators of seizure susceptibility and role in the treatment of epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV. Editors. Jasper's Basic Mechanisms of the Epilepsies. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.

Epilepsy foundation. Available at http:// etp/pipeline_new_therapies. Accessed on 3 March 2016.

Weisenberg JLZ, Wong M. Profile of ezogabine (retigabine) and its potential as an adjunctive treatment for patients with partial-onset seizures. Neuropsychiatr Dis Treat. 2011;7:409-14.

Hempel R, Schupke H, McNelly PJ, Hei-necke K, Kronbach C, Grunwald C, et al. Metabolism of Retigabine (D-23129), A novel anticonvulsant. Drug Metab Dis. 1999;27:613-22.

Rundfeldt C, Netzer R. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transfected with human KCNQ2/3 subunits. Neurosci Lett. 2000;282(1-2):73-6.

Harris JA, Murphy JA. Retigabine (ezogabine) as add-on therapy for partial-onset seizures: an update for clinicians. Therapeutic Advances in Chronic Disease. 2011;2(6):371-6.

Hempel R, Schupke H, McNeilly PJ, Heinecke K, Kronbach C, Grunwald C, et al. Metabolism of retigabine (D-23129), a novel anticonvulsant. Drug Metab Dispos. 1999;27(5):613-22.

Tikoo D, Gupta M. Retigabine (Ezogabine) for management of partial onset seizures: A mini review. Int J Pharmacol and Clin Sci. 2012;1:85-90.

Bialer M, Johannessenb SI, Levyc RH, Peruccad E, Tomsone T, Whitef HS. Progress report on new antiepileptic drugs: a summary of the eleventh eilat conference (EILAT XI). Epilepsy Research. 2013;103:2-30.

Shih JJ, Tatum WO, Rudzinski LA. New drug classes for the treatment of partial onset epilepsy: focus on perampanel. Therapeutics and Clinical Risk Management. 2013;9:285-93.

Franco V, Crema F, Iudice A, Zaccara G, Grillo E. Novel treatment options for epilepsy: focus on perampanel. Pharmacol Res. 2013;70(1):35-40.

Biton V, Berkovic SF, Abou KB, Sperling MR, Johnson ME, Brivaracetam LS. As adjunctive treatment for uncontrolled partial epilepsy in adults: a phase iii randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55:57-66.

Shekh AT, Hen N, McDonough JH, Yagen B, Bialer M. Valnoctamide and sec-butyl-propylacetamide (SPD) for acute seizures and status epilepticus. Epilepsia. 2013;54(l6):99-102.