Literature DB >> 21180561

Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilepsy revisited.

Rainer Surges1, Kirill E Volynski, Matthew C Walker.   

Abstract

Levetiracetam (LEV) is a new antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes as sole or add-on medication. Nevertheless, its underlying mechanism of action is poorly understood. It has a unique preclinical profile; unlike other antiepileptic drugs (AEDs), it modulates seizure-activity in animal models of chronic epilepsy with no effect in most animal models of acute seizures. Yet it is effective in acute in-vitro 'seizure' models. A possible explanation for these dichotomous findings is that LEV has different mechanisms of actions, whether given acutely or chronically and in 'epileptic' and control tissue. Here we review the general mechanism of action of AEDs, give an updated and critical overview about the experimental findings of LEV's cellular targets (in particular the synaptic vesicular protein SV2A) and ask whether LEV represents a new class of AED.

Entities:  

Keywords:  SV2A; antiepileptic drugs; epilepsy; ion channels; levetiracetam; synaptic transmission

Year:  2008        PMID: 21180561      PMCID: PMC3002539          DOI: 10.1177/1756285608094212

Source DB:  PubMed          Journal:  Ther Adv Neurol Disord        ISSN: 1756-2856            Impact factor:   6.570


  74 in total

Review 1.  Structure and regulation of voltage-gated Ca2+ channels.

Authors:  W A Catterall
Journal:  Annu Rev Cell Dev Biol       Date:  2000       Impact factor: 13.827

Review 2.  Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission.

Authors:  David J Dooley; Charles P Taylor; Sean Donevan; Douglas Feltner
Journal:  Trends Pharmacol Sci       Date:  2007-01-10       Impact factor: 14.819

3.  Anticonvulsant efficacy of gabapentin and levetiracetam in phenytoin-resistant kindled rats.

Authors:  W Löscher; E Reissmüller; U Ebert
Journal:  Epilepsy Res       Date:  2000-06       Impact factor: 3.045

4.  Levetiracetam (ucb LO59) affects in vitro models of epilepsy in CA3 pyramidal neurons without altering normal synaptic transmission.

Authors:  S Birnstiel; E Wülfert; S G Beck
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  1997-11       Impact factor: 3.000

5.  Carbamazepine inhibits L-type Ca2+ channels in cultured rat hippocampal neurons stimulated with glutamate receptor agonists.

Authors:  A F Ambrósio; A P Silva; J O Malva; P Soares-da-Silva; A P Carvalho; C M Carvalho
Journal:  Neuropharmacology       Date:  1999-09       Impact factor: 5.250

6.  The novel antiepileptic drug levetiracetam (ucb L059) induces alterations in GABA metabolism and turnover in discrete areas of rat brain and reduces neuronal activity in substantia nigra pars reticulata.

Authors:  W Löscher; D Hönack; P Bloms-Funke
Journal:  Brain Res       Date:  1996-10-07       Impact factor: 3.252

7.  Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents.

Authors:  S M Todorovic; C J Lingle
Journal:  J Neurophysiol       Date:  1998-01       Impact factor: 2.714

8.  The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels.

Authors:  Adam C Errington; Thomas Stöhr; Cara Heers; George Lees
Journal:  Mol Pharmacol       Date:  2007-10-16       Impact factor: 4.436

9.  Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats.

Authors:  Heidrun Potschka; Steffen Baltes; Wolfgang Löscher
Journal:  Epilepsy Res       Date:  2004-02       Impact factor: 3.045

10.  Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons.

Authors:  Mikael Angehagen; Doru Georg Margineanu; Elinor Ben-Menachem; Lars Rönnbäck; Elisabeth Hansson; Henrik Klitgaard
Journal:  Neuroreport       Date:  2003-03-03       Impact factor: 1.837

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  28 in total

1.  New treatment options in status epilepticus: a critical review on intravenous levetiracetam.

Authors:  Eugen Trinka; Judith Dobesberger
Journal:  Ther Adv Neurol Disord       Date:  2009-03       Impact factor: 6.570

2.  Prediction of off-target drug effects through data fusion.

Authors:  Emmanuel R Yera; Ann E Cleves; Ajay N Jain
Journal:  Pac Symp Biocomput       Date:  2014

3.  Levetiracetam-induced acute psychotic episode.

Authors:  Srinivas Dannaram; Dileep Borra; Madhuri Pulluri; Prachi Jindal; Ashish Sharma
Journal:  Innov Clin Neurosci       Date:  2012-10

4.  Radiosynthesis of (11)C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression.

Authors:  Hancheng Cai; Thomas J Mangner; Otto Muzik; Ming-Wei Wang; Diane C Chugani; Harry T Chugani
Journal:  ACS Med Chem Lett       Date:  2014-08-19       Impact factor: 4.345

Review 5.  Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms.

Authors:  Rainer Surges; Roland D Thijs; Hanno L Tan; Josemir W Sander
Journal:  Nat Rev Neurol       Date:  2009-08-11       Impact factor: 42.937

Review 6.  Molecular aspects of age-related cognitive decline: the role of GABA signaling.

Authors:  Joseph A McQuail; Charles J Frazier; Jennifer L Bizon
Journal:  Trends Mol Med       Date:  2015-06-09       Impact factor: 11.951

Review 7.  Do antiepileptic drugs increase the risk of infectious diseases? A meta-analysis of placebo-controlled studies.

Authors:  Gaetano Zaccara; Fabio Giovannelli; Filippo Sean Giorgi; Valentina Franco; Sara Gasparini; Francesco Mandò Tacconi
Journal:  Br J Clin Pharmacol       Date:  2017-05-07       Impact factor: 4.335

8.  Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme.

Authors:  Melissa Kerkhof; Janneke C M Dielemans; Melanie S van Breemen; Hanneke Zwinkels; Robert Walchenbach; Martin J Taphoorn; Charles J Vecht
Journal:  Neuro Oncol       Date:  2013-05-16       Impact factor: 12.300

Review 9.  Seizure prognosis in brain tumors: new insights and evidence-based management.

Authors:  Charles J Vecht; Melissa Kerkhof; Alberto Duran-Pena
Journal:  Oncologist       Date:  2014-06-04

10.  Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions.

Authors:  William R Garnett; Erik K St Louis; Thomas R Henry; Thomas Bramley
Journal:  Curr Neuropharmacol       Date:  2009-06       Impact factor: 7.363

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