Advertisement

Molecular Neurobiology

, Volume 51, Issue 2, pp 599–609 | Cite as

Specific Binding of Lacosamide to Collapsin Response Mediator Protein 2 (CRMP2) and Direct Impairment of its Canonical Function: Implications for the Therapeutic Potential of Lacosamide

  • Sarah M. Wilson
  • Rajesh Khanna
Article

Abstract

The novel antiepileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide’s ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e., seizures). While the role of CRMP2 in epilepsy has not been well studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease modifying. Recently, however, the validity of lacosamide’s interaction with CRMP2 has come under scrutiny. In this review, we address the contradictory reports concerning the binding of lacosamide to CRMP2 as well as the ability of lacosamide to directly impact CRMP2 function. Additionally, we address similarly the contradicting reports regarding the potential disease-modifying effect of lacosamide on the development and progression of epilepsy. As the vast majority of antiepileptic drugs influences only the symptoms of epilepsy, the ability to hinder disease progression would be a major breakthrough in efforts to cure or prevent this debilitating syndrome.

Keywords

Lacosamide CRMP2 Sodium channels Slow inactivation Epileptogenesis 

References

  1. 1.
    Biton V (2012) Lacosamide for the treatment of partial-onset seizures. Expert Rev Neurother 12(6):645–655. doi: 10.1586/ern.12.50 PubMedCrossRefGoogle Scholar
  2. 2.
    Cortes S, Liao ZK, Watson D, Kohn H (1985) Effect of structural modification of the hydantoin ring on anticonvulsant activity. J Med Chem 28(5):601–606PubMedCrossRefGoogle Scholar
  3. 3.
    Choi D, Stables JP, Kohn H (1996) The anticonvulsant activities of functionalized N-benzyl 2-acetamidoacetamides. The importance of the 2-acetamido substituent. Bioorg Med Chem 4(12):2105–2114PubMedCrossRefGoogle Scholar
  4. 4.
    Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Loiseau P, Perucca E (2001) Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V). Epilepsy Res 43(1):11–58PubMedCrossRefGoogle Scholar
  5. 5.
    Duncan GE, Kohn H (2005) The novel antiepileptic drug lacosamide blocks behavioral and brain metabolic manifestations of seizure activity in the 6 Hz psychomotor seizure model. Epilepsy Res 67(1–2):81–87. doi: 10.1016/j.eplepsyres.2005.08.009 PubMedCrossRefGoogle Scholar
  6. 6.
    Stöhr T, Kupferberg HJ, Stables JP, Choi D, Harris RH, Kohn H, Walton N, White HS (2007) Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy. Epilepsy Res 74(2–3):147–154. doi: 10.1016/j.eplepsyres.2007.03.004 PubMedCrossRefGoogle Scholar
  7. 7.
    Perucca E, Yasothan U, Clincke G, Kirkpatrick P (2008) Lacosamide. Nat Rev Drug Discov 7(12):973–974PubMedCrossRefGoogle Scholar
  8. 8.
  9. 9.
    Markoula S, Teotonio R, Ratnaraj N, Duncan JS, Sander JW, Patsalos PN (2014) Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs. Ther Drug Monit. doi: 10.1097/FTD.0000000000000051 PubMedGoogle Scholar
  10. 10.
    Chung S, Ben-Menachem E, Sperling MR, Rosenfeld W, Fountain NB, Benbadis S, Hebert D, Isojarvi J, Doty P (2010) Examining the clinical utility of lacosamide: Pooled analyses of three phase II/III clinical trials. CNS Drugs 24(12):1041–1054. doi: 10.2165/11586830-000000000-00000 PubMedCrossRefGoogle Scholar
  11. 11.
    Beydoun A, D’Souza J, Hebert D, Doty P (2009) Lacosamide: Pharmacology, mechanisms of action and pooled efficacy and safety data in partial-onset seizures. Expert Rev Neurother 9(1):33–42. doi: 10.1586/14737175.9.1.33 PubMedCrossRefGoogle Scholar
  12. 12.
    Errington AC, Coyne L, Stohr T, Selve N, Lees G (2006) Seeking a mechanism of action for the novel anticonvulsant lacosamide. Neuropharmacology 50(8):1016–1029. doi: 10.1016/j.neuropharm.2006.02.002 PubMedCrossRefGoogle Scholar
  13. 13.
    Errington AC, Stohr T, Heers C, Lees G (2008) The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Mol Pharmacol 73(1):157–169PubMedCrossRefGoogle Scholar
  14. 14.
    Beyreuther BK, Freitag J, Heers C, Krebsfanger N, Scharfenecker U, Stohr T (2007) Lacosamide: a review of preclinical properties. CNS Drug Rev 13(1):21–42PubMedCrossRefGoogle Scholar
  15. 15.
    Park KD, Morieux P, Salome C, Cotten SW, Reamtong O, Eyers C, Gaskell SJ, Stables JP, Liu R, Kohn H (2009) Lacosamide isothiocyanate-based agents: novel agents to target and identify lacosamide receptors. J Med Chem 52(21):6897–6911PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Park KD, Stables JP, Liu R, Kohn H (2010) Proteomic searches comparing two (R)-lacosamide affinity baits: an electrophilic arylisothiocyanate and a photoactivated arylazide group. Org Biomol Chem 8(12):2803–2813. doi: 10.1039/c000987c PubMedCrossRefGoogle Scholar
  17. 17.
    Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16(19):6197–6207PubMedGoogle Scholar
  18. 18.
    Schmidt EF, Strittmatter SM (2007) The CRMP family of proteins and their role in Sema3A signaling. Adv Exp Med Biol 600:1–11PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Charrier E, Reibel S, Rogemond V, Aguera M, Thomasset N, Honnorat J (2003) Collapsin response mediator proteins (CRMPs): Involvement in nervous system development and adult neurodegenerative disorders. Mol Neurobiol 28(1):51–64PubMedCrossRefGoogle Scholar
  20. 20.
    Hensley K, Venkova K, Christov A, Gunning W, Park J (2011) Collapsin response mediator protein-2: an emerging pathologic feature and therapeutic target for neurodisease indications. Molecular Neurobiology 43(3):180–91PubMedCrossRefGoogle Scholar
  21. 21.
    Fukata Y, Itoh TJ, Kimura T, Menager C, Nishimura T, Shiromizu T, Watanabe H, Inagaki N, Iwamatsu A, Hotani H, Kaibuchi K (2002) CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat Cell Biol 4(8):583–591PubMedGoogle Scholar
  22. 22.
    Chae YC, Lee S, Heo K, Ha SH, Jung Y, Kim JH, Ihara Y, Suh PG, Ryu SH (2009) Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity. Cell Signal 21(12):1818–1826. doi: 10.1016/j.cellsig.2009.07.017 PubMedCrossRefGoogle Scholar
  23. 23.
    Arimura N, Inagaki N, Chihara K, Menager C, Nakamura N, Amano M, Iwamatsu A, Goshima Y, Kaibuchi K (2000) Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse. J Biol Chem 275(31):23973–23980PubMedCrossRefGoogle Scholar
  24. 24.
    Brown M, Jacobs T, Eickholt B, Ferrari G, Teo M, Monfries C, Qi RZ, Leung T, Lim L, Hall C (2004) Alpha2-chimaerin, cyclin-dependent Kinase 5/p35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse. J Neurosci: Off J Soc Neurosci 24(41):8994–9004. doi: 10.1523/jneurosci.3184-04.2004 CrossRefGoogle Scholar
  25. 25.
    Cole AR, Knebel A, Morrice NA, Robertson LA, Irving AJ, Connolly CN, Sutherland C (2004) GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons. J Biol Chem 279(48):50176–50180. doi: 10.1074/jbc.C400412200 PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Arimura N, Menager C, Kawano Y, Yoshimura T, Kawabata S, Hattori A, Fukata Y, Amano M, Goshima Y, Inagaki M, Morone N, Usukura J, Kaibuchi K (2005) Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones. Mol Cell Biol 25(22):9973–9984PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Uchida Y, Ohshima T, Yamashita N, Ogawara M, Sasaki Y, Nakamura F, Goshima Y (2009) Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32. J Biol Chem 284(40):27393–27401. doi: 10.1074/jbc.M109.000240 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, Nakamura F, Takei K, Ihara Y, Mikoshiba K, Kolattukudy P, Honnorat J, Goshima Y (2005) Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: Implication of common phosphorylating mechanism underlying axon guidance and Alzheimer’s disease. Genes Cells 10(2):165–179PubMedCrossRefGoogle Scholar
  29. 29.
    Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K (2005) GSK-3[beta] regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120(1):137–149. doi: 10.1016/j.cell.2004.11.012 PubMedCrossRefGoogle Scholar
  30. 30.
    Cole AR, Causeret F, Yadirgi G, Hastie CJ, McLauchlan H, McManus EJ, Hernandez F, Eickholt BJ, Nikolic M, Sutherland C (2006) Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo. J Biol Chem 281(24):16591–16598. doi: 10.1074/jbc.M513344200 PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Hou ST, Jiang SX, Aylsworth A, Ferguson G, Slinn J, Hu H, Leung T, Kappler J, Kaibuchi K (2009) CaMKII phosphorylates collapsin response mediator protein 2 and modulates axonal damage during glutamate excitotoxicity. J Neurochem 111(3):870–881PubMedCrossRefGoogle Scholar
  32. 32.
    Brittain JM, Chen L, Wilson SM, Brustovetsky T, Gao X, Ashpole NM, Molosh AI, You H, Hudmon A, Shekhar A, White FA, Zamponi GW, Brustovetsky N, Chen J, Khanna R (2011) Neuroprotection against traumatic brain injury by a peptide derived from the collapsin response mediator protein 2 (CRMP2). J Biol Chem 286(43):37778–37792. doi: 10.1074/jbc.M111.255455 PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Brittain JM, Pan R, You H, Brustovetsky T, Brustovetsky N, Zamponi GW, Lee WH, Khanna R (2012) Disruption of NMDAR-CRMP-2 signaling protects against focal cerebral ischemic damage in the rat middle cerebral artery occlusion model. Channels (Austin) 6(1):52–9CrossRefGoogle Scholar
  34. 34.
    Nishimura T, Fukata Y, Kato K, Yamaguchi T, Matsuura Y, Kamiguchi H, Kaibuchi K (2003) CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nat Cell Biol 5(9):819–826PubMedCrossRefGoogle Scholar
  35. 35.
    Kawano Y, Yoshimura T, Tsuboi D, Kawabata S, Kaneko-Kawano T, Shirataki H, Takenawa T, Kaibuchi K (2005) CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Mol Cell Biol 25(22):9920–9935. doi: 10.1128/MCB.25.22.9920-9935.2005 PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Kimura T, Watanabe H, Iwamatsu A, Kaibuchi K (2005) Tubulin and CRMP-2 complex is transported via Kinesin-1. J Neurochem 93(6):1371–1382PubMedCrossRefGoogle Scholar
  37. 37.
    Lykissas MG, Batistatou AK, Charalabopoulos KA, Beris AE (2007) The role of neurotrophins in axonal growth, guidance, and regeneration. Curr Neurovasc Res 4(2):143–151PubMedCrossRefGoogle Scholar
  38. 38.
    Arimura N, Kimura T, Nakamuta S, Taya S, Funahashi Y, Hattori A, Shimada A, Ménager C, Kawabata S, Fujii K, Iwamatsu A, Segal RA, Fukuda M, Kaibuchi K (2009) Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell 16(5):675–686. doi: 10.1016/j.devcel.2009.03.005 PubMedCrossRefGoogle Scholar
  39. 39.
    Rahajeng J, Giridharan SS, Naslavsky N, Caplan S (2010) Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory proteins to dynein motors. J Biol Chem 85(42):31918–22CrossRefGoogle Scholar
  40. 40.
    Khanna R, Wilson SM, Brittain JM, Weimer J, Sultana R, Butterfield A, Hensley K (2012) Opening Pandora’s jar: a primer on the putative roles of CRMP2 in a panoply of neurodegenerative, sensory and motor neuron, and central disorders. Future Neurol 7(6):749–771. doi: 10.2217/fnl.12.68 PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Beyreuther B, Stohr T, Freitag J (2009) Method for identifying crmp modulators. Google PatentsGoogle Scholar
  42. 42.
    Park KD, Kim D, Reamtong O, Eyers C, Gaskell SJ, Liu R, Kohn H (2011) Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 zeta. J Am Chem Soc 133(29):11320–11330. doi: 10.1021/ja2034156 PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Wang Y, Brittain JM, Jarecki BW, Park KD, Wilson SM, Wang B, Hale R, Meroueh SO, Cummins TR, Khanna R (2010) In silico docking and electrophysiological characterization of lacosamide binding sites on collapsin response mediator protein 2 (CRMP-2) identifies a pocket important in modulating sodium channel slow inactivation. J Biol Chem 285(33):25296–307PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Sousa SF, Fernandes PA, Ramos MJ (2006) Protein-ligand docking: Current status and future challenges. Proteins 65(1):15–26. doi: 10.1002/prot.21082 PubMedCrossRefGoogle Scholar
  45. 45.
    Delorenzo RJ, Sun DA, Deshpande LS (2005) Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy. Pharmacol Ther 105(3):229–266. doi: 10.1016/j.pharmthera.2004.10.004 PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Wang Y, Khanna R (2011) Calcium channels are not affected by the anti-epileptic drug lacosamide. Transl Neurosci 2(1):13–22PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Zhang JF, Randall AD, Ellinor PT, Horne WA, Sather WA, Tanabe T, Schwarz TL, Tsien RW (1993) Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacology 32(11):1075–1088PubMedCrossRefGoogle Scholar
  48. 48.
    Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87(4):387–406PubMedCentralPubMedGoogle Scholar
  49. 49.
    Wilson SM, Xiong W, Wang Y, Ping X, Head JD, Brittain JM, Gagare PD, Ramachandran PV, Jin X, Khanna R (2012) Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization. Neuroscience 210:451–466. doi: 10.1016/j.neuroscience.2012.02.038 PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Wolff C, Carrington B, Varrin-Doyer M, Vandendriessche A, Van der Perren C, Famelart M, Gillard M, Foerch P, Rogemond V, Honnorat J, Lawson A, Miller K (2012) Drug binding assays do not reveal specific binding of lacosamide to collapsin response mediator protein 2 (CRMP-2). CNS Neurosci Ther 18(6):493–500. doi: 10.1111/j.1755-5949.2012.00313.x PubMedCrossRefGoogle Scholar
  51. 51.
    Johnsson B, Lofas S, Lindquist G (1991) Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors. Anal Biochem 198(2):268–277PubMedCrossRefGoogle Scholar
  52. 52.
    Phizicky EM, Fields S (1995) Protein-protein interactions: Methods for detection and analysis. Microbiol Rev 59(1):94–123PubMedCentralPubMedGoogle Scholar
  53. 53.
    Wienken CJ, Baaske P, Rothbauer U, Braun D, Duhr S (2010) Protein-binding assays in biological liquids using microscale thermophoresis. Nat Commun 1:100. doi: 10.1038/ncomms1093 PubMedCrossRefGoogle Scholar
  54. 54.
    Chang BS, Lowenstein DH (2003) Epilepsy. N Engl J Med 349(13):1257–1266. doi: 10.1056/NEJMra022308 PubMedCrossRefGoogle Scholar
  55. 55.
    Salin P, Tseng GF, Hoffman S, Parada I, Prince DA (1995) Axonal sprouting in layer V pyramidal neurons of chronically injured cerebral cortex. J Neurosci: Off J Soc Neurosci 15(12):8234–8245Google Scholar
  56. 56.
    Golarai G, Greenwood AC, Feeney DM, Connor JA (2001) Physiological and structural evidence for hippocampal involvement in persistent seizure susceptibility after traumatic brain injury. J Neurosci: Off J Soc Neurosci 21(21):8523–8537Google Scholar
  57. 57.
    Kharatishvili I, Nissinen JP, McIntosh TK, Pitkanen A (2006) A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats. Neuroscience 140(2):685–697. doi: 10.1016/j.neuroscience.2006.03.012 PubMedCrossRefGoogle Scholar
  58. 58.
    Jin X, Prince DA, Huguenard JR (2006) Enhanced excitatory synaptic connectivity in layer v pyramidal neurons of chronically injured epileptogenic neocortex in rats. J Neurosci 26(18):4891–4900PubMedCrossRefGoogle Scholar
  59. 59.
    Graber KD, Prince DA (2004) A critical period for prevention of posttraumatic neocortical hyperexcitability in rats. Ann Neurol 55(6):860–870. doi: 10.1002/ana.20124 PubMedCrossRefGoogle Scholar
  60. 60.
    Prince DA, Parada I, Scalise K, Graber K, Jin X, Shen F (2009) Epilepsy following cortical injury: Cellular and molecular mechanisms as targets for potential prophylaxis. Epilepsia 50:30–40. doi: 10.1111/j.1528-1167.2008.02008.x PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    McKinney RA, Debanne D, Gahwiler BH, Thompson SM (1997) Lesion-induced axonal sprouting and hyperexcitability in the hippocampus in vitro: Implications for the genesis of posttraumatic epilepsy. Nat Med 3(9):990–996PubMedCrossRefGoogle Scholar
  62. 62.
    Czech T, Yang JW, Csaszar E, Kappler J, Baumgartner C, Lubec G (2004) Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy. Neurochem Res 29(12):2189–2196PubMedCrossRefGoogle Scholar
  63. 63.
    Bretin S, Reibel S, Charrier E, Maus-Moatti M, Auvergnon N, Thevenoux A, Glowinski J, Rogemond V, Premont J, Honnorat J, Gauchy C (2005) Differential expression of CRMP1, CRMP2A, CRMP2B, and CRMP5 in axons or dendrites of distinct neurons in the mouse brain. J Comp Neurol 486(1):1–17. doi: 10.1002/cne.20465 PubMedCrossRefGoogle Scholar
  64. 64.
    Zhang Z, Ottens AK, Sadasivan S, Kobeissy FH, Fang T, Hayes RL, Wang KK (2007) Calpain-mediated collapsin response mediator protein-1, -2, and -4 proteolysis after neurotoxic and traumatic brain injury. J Neurotrauma 24(3):460–472. doi: 10.1089/neu.2006.0078 PubMedCrossRefGoogle Scholar
  65. 65.
    Brown M, Jacobs T, Eickholt B, Ferrari G, Teo M, Monfries C, Qi RZ, Leung T, Lim L, Hall C (2004) Alpha2-chimaerin, cyclin-dependent Kinase 5/p35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse. J Neurosci 24(41):8994–9004PubMedCrossRefGoogle Scholar
  66. 66.
    Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, Nakamura F, Takei K, Ihara Y, Mikoshiba K, Kolattukudy P, Honnorat J, Goshima Y (2005) Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: Implication of common phosphorylating mechanism underlying axon guidance and Alzheimer’s disease. Genes Cells: Devoted Mol Cell Mech 10(2):165–179. doi: 10.1111/j.1365-2443.2005.00827.x CrossRefGoogle Scholar
  67. 67.
    Sato Y, Ishida-Nakajima W, Kawamura M, Miura S, Oguma R, Arai H, Takahashi T (2011) Hypoxia-ischemia induces hypo-phosphorylation of collapsin response mediator protein 2 in a neonatal rat model of periventricular leukomalacia. Brain Res 1386:165–174. doi: 10.1016/j.brainres.2011.02.027 PubMedCrossRefGoogle Scholar
  68. 68.
    Wilson SM, Yeon SK, Yang XF, Park KD, Khanna R (2014) Differential regulation of collapsin response mediator protein 2 (CRMP2) phosphorylation by GSK3ß and CDK5 following traumatic brain injury. Front Cell Neurosci 8:14. doi: 10.3389/fncel.2014.00135 Google Scholar
  69. 69.
    Lee C-Y, Jaw T, Tseng H-C, Chen IC, Liou H-H (2012) Lovastatin modulates glycogen synthase kinase-3β pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus. PLoS One 7(6):e38789. doi: 10.1371/journal.pone.0038789 PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Brandt C, Heile A, Potschka H, Stoehr T, Löscher W (2006) Effects of the novel antiepileptic drug lacosamide on the development of amygdala kindling in rats. Epilepsia 47(11):1803–1809. doi: 10.1111/j.1528-1167.2006.00818.x PubMedCrossRefGoogle Scholar
  71. 71.
    Loscher W, Brandt C (2010) Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacol Rev 62(4):668–700. doi: 10.1124/pr.110.003046 PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Loscher W (2002) Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res 50(1–2):105–123PubMedCrossRefGoogle Scholar
  73. 73.
    Loscher W, Honack D, Rundfeldt C (1998) Antiepileptogenic effects of the novel anticonvulsant levetiracetam (ucb L059) in the kindling model of temporal lobe epilepsy. J Pharmacol Exp Ther 284(2):474–479PubMedGoogle Scholar
  74. 74.
    Wasterlain CG, Stohr T, Matagne A (2011) The acute and chronic effects of the novel anticonvulsant lacosamide in an experimental model of status epilepticus. Epilepsy Res 94(1–2):10–17. doi: 10.1016/j.eplepsyres.2010.12.014 PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Wang B, Dawson H, Wang H, Kernagis D, Kolls BJ, Yao L, Laskowitz DT (2012) Lacosamide improves outcome in a murine model of traumatic brain injury. Neurocrit Care. doi: 10.1007/s12028-012-9808-8 Google Scholar
  76. 76.
    Pitkanen A, Immonen R, Ndode-Ekane X, Grohn O, Stohr T, Nissinen J (2014) Effect of lacosamide on structural damage and functional recovery after traumatic brain injury in rats. Epilepsy Res 108(4):653–665. doi: 10.1016/j.eplepsyres.2014.02.001 PubMedCrossRefGoogle Scholar
  77. 77.
    Licko T, Seeger N, Zellinger C, Russmann V, Matagne A, Potschka H (2013) Lacosamide treatment following status epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical status epilepticus model. Epilepsia. doi: 10.1111/epi.12196 PubMedGoogle Scholar
  78. 78.
    Santhakumar V, Aradi I, Soltesz I (2005) Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography. J Neurophysiol 93(1):437–453. doi: 10.1152/jn.00777.2004 PubMedCrossRefGoogle Scholar
  79. 79.
    Heng K, Haney MM, Buckmaster PS (2013) High-dose rapamycin blocks mossy fiber sprouting but not seizures in a mouse model of temporal lobe epilepsy. Epilepsia 54(9):1535–1541. doi: 10.1111/epi.12246 PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Verrotti A, Loiacono G, Pizzolorusso A, Parisi P, Bruni O, Luchetti A, Zamponi N, Cappanera S, Grosso S, Kluger G, Janello C, Franzoni E, Elia M, Spalice A, Coppola G, Striano P, Pavone P, Savasta S, Viri M, Romeo A, Aloisi P, Gobbi G, Ferretti A, Cusmai R, Curatolo P (2013) Lacosamide in pediatric and adult patients: comparison of efficacy and safety. Seizure: J Br Epilepsy Assoc 22(3):210–216. doi: 10.1016/j.seizure.2012.12.009 CrossRefGoogle Scholar
  81. 81.
    Kim JS, Kim H, Lim BC, Chae JH, Choi J, Kim KJ, Hwang YS, Hwang H (2013) Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy. Brain Dev. doi: 10.1016/j.braindev.2013.07.003 Google Scholar
  82. 82.
    Grosso S, Parisi P, Spalice A, Verrotti A, Balestri P (2014) Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy. Eur J Paediatr Neurol: EJPN: Off J Eur Paediatr Neurol Soc 18(1):55–59. doi: 10.1016/j.ejpn.2013.08.006 CrossRefGoogle Scholar
  83. 83.
    Tomson T, Landmark CJ, Battino D (2013) Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications. Epilepsia 54(3):405–414. doi: 10.1111/epi.12109 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Paul and Carole Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Pharmacology and Neuroscience Graduate Interdisciplinary Program, College of MedicineUniversity of ArizonaTucsonUSA

Personalised recommendations