Use of SV2A antagonist for the epilepsy treatment

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Tipada Samseethong


          Epilepsy is the third of the common neurological condition affecting individuals of all ages. Pharmacotherapy is the first line and is the primary treatment for providing to control epilepsy and seizure that antiepileptic drugs were developed ongoing. The US Food Drug Administration (FDA) and European approved brivaracetam as adjunctive therapy for treatment partial-onset seizure in patients with epilepsy. Brivaracetam, a selective synaptic vesicle protein 2A inhibitor as same as levetiracetam, has a high specificity target SV2A about 10-30 times than levetiracetam. The pharmacokinetic profiles of these drugs present a rapid and complete absorption, low molecular with low binding plasma protein. However, brivaracetam has a more lipophilicity than levetiracetam. In animal study, lipophilicity is a key for drug penetration in to the brain thus brivaracetam has a faster entry to the brain than levetiracetam. The onset of brivaracetam is approximately 1 hr while levetiracetam is 2 hr from complete absorption. Moreover, brivaracetam is metabolized primarily via liver (major CYP 2C8 and CYP 2C19) while levetiracetam does not undergo extensive metabolism but it is excreted unchanged by renal. The direct efficacy assessment between these two drugs has not been studies yet. Other studies showed that 50 milligram brivaracetam and 1000 milligram levetiracetam can reduced seizure frequency more than placebo. Untorelate side effects has found in brivaracetam 100 milligram/day and levetiracetam 2000 milligram/day. The serious adverse of psychological conditions has 93.4% reduction when switching leveteracetam to brivaracetam.


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Review Article


Abraham S, Shaju M. Innovations in epilepsy management - an overview. J Pharm Pharm Sci. 2013; 16: 564-76.
Ben-Menachem E and Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levitiracetam Study Group. Epilepsia. 2000; 41: 1276-83.
Biton V, Berkovic SF, Abou-Khalil B, et al. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized,double-blind, placebo-controlled trial. Epilepsia 2014; 55: 57–66.
Bona JR. Treatment of neuroleptic-induced tardive dyskinesia with levetiracetam: a case series. J clin psychopharmacol. 2006; 26: 215-6.
Brighina F, Palermo A, Aloisio A, Francolini M, Giglia G, Fierro B. Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label study. Clinical neuropharmacol. 2006; 29: 338-42.
Brodie MJ, Perucca E, Ryvlin P, et al. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology. 2007; 68: 402-8.
Cereghino JJ, Biton V, Abou-Khalil B, et al. 2000. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000; 55: 236–42.
Drug@FDA:FDA Approved Drug Products [online]. 2009 [cited by April 20, 2018]. Available from:,021505s021s024lbl.pdf.
Drug@FDA:FDA Approved Drug Products [online]. 2017 [cited by Sep 20, 2017]. Available from:,021505s021s024lbl.pdf.
Drug@FDA:FDA Approved Drug Products [online]. 2017 [cited by Sep 20, 2017]. Available from:
Elberry AA, Felemban RK, Hareeri RH, et al. Efficacy and safety of levetiracetam in pediatric epilepsy. Saudi Pharm J. 2012; 1: 81-4.
European medicines agency Science medicines health [online]. 2013 [cited by sep 20, 2017]. Available from:
European medicines agency Science medicines health [online]. 2015 [cited by sep 20, 2017]. Available from:
Feys P, D'Hooghe M B, Nagels G, Helsen WF. The effect of levetiracetam on tremor severity and functionality in patients with multiple sclerosis. Mult Scler. 2009; 15: 371-8.
Gillard M, Fuks B, Leclercq K, Matagne. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain:relationship to anti-convulsantproperties. Eur J Pharmacol. 2011; 664: 36–44.
Hawker K, Frohman E, Racke M. Levetiracetam for phasic spasticity in multiple sclerosis. Arch neurol. 2003; 60: 1772-4.
Klein P, Schiemann J, Sperling MR, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015; 56: 1890–1898.
Klitgaard H, Matagne A, Nicolas JM, et al. Brivaracetam: Rationale for discove and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016; 57: 538-48.
Konitsiotis S, Pappa S, Mantas C, Mavreas V. Levetiracetam in tardive dyskinesia: an open label study. Mov Disord. 2006; 21: 1219-21.
Lynch BA, Lambeng N, Nocka K, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004; 101: 9861-6.
Mbizvo GK, Dixon P, Hutton JL, et al. Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane Review. Cochrane Database Syst Rev. 2012 ;12: 1-78.
Mirza UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus: a randomized, open labelled pilot study. J Neurol. 2012; 259: 645-8.
Nau R, Sörgel F and Eiffert H. Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections. Clin Microbiol Rev. 2010; 23: 858–83.
Nicolas JM, Hannestad J, Holden D, et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016; 57: 201–9.
Noachtar S, Andermann E, Meyvisch P, et al. Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. Neurology. 2008; 70: 607–16.
Price MJ. Levetiracetam in the treatment of neuropathic pain: three case studies. Clin J Pain. 2004; 20: 33-6.
Rogawski MA. A New SV2A Ligand for Epilepsy. Cell. 2016; 167: 587.
Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, et al. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014; 55: 47–56.
Sargentini-Maier ML, Rolan P, Connell J, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol. 2007; 63: 680-8.
Shorvon SD, Lowenthal A, Janz D, et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam study Group. Epilepsia. 2000; 41: 1179-86.
Stockis A, Sargentini-Maier ML, Horsmans Y. Brivaracetam disposition in mild to severe hepatic impairment. J Clin Pharmacol. 2013; 53: 633-41.
World Health Organization. Epilepsy Fact sheet [online]. 2017 [cited by Sep 20, 2017]. Available from: en/.
Xu T, Bajjalieh SM. SV2 modulates the size of the readily releasable pool of secretory vesicles. Nature Cell Biol. 2001; 3: 691–8.
Yates SL, Fakhoury T, Liang W, et al. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015; 52: 165-8.
Zesiewicz TA, Sullivan KL, Maldonado JL, Tatum WO, Hauser RA. Open-label pilot study of levetiracetam (Keppra) for the treatment of levodopa-induced dyskinesias in Parkinson's disease. Mov Disord. 2005; 20: 1205-9.
Zhang L, Li S, Li H, ZOU X. Levetiracetam vs. brivaracetam for adults with refractory focal seizures: A meta-analysis and indirect comparison. Seizure. 2016; 39: 28-33.