Epilepsy Research
Volume 83, Issue 1 , Pages 66-72 , January 2009

Carisbamate, a novel neuromodulator, inhibits voltage-gated sodium channels and action potential firing of rat hippocampal neurons

  • Yi Liu

      Affiliations

    • Analgesics Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States
    • Corresponding Author InformationCorresponding author. Tel.: +1 215 628 5427; fax: +1 215 628 3297.
    • ,
  • George J. Yohrling

      Affiliations

    • CNS Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States
    • ,
  • Yan Wang

      Affiliations

    • Analgesics Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States
    • ,
  • Tasha L. Hutchinson

      Affiliations

    • Analgesics Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States
    • ,
  • Douglas E. Brenneman

      Affiliations

    • CNS Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States
    • ,
  • Christopher M. Flores

      Affiliations

    • Analgesics Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States
    • ,
  • Boyu Zhao

      Affiliations

    • CNS Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA 19477-0776, United States

Received 28 April 2008 ,Revised 18 September 2008 ,Accepted 23 September 2008.

References 

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  2. Costa PF. The kinetic parameters of sodium currents in maturing acutely isolated rat hippocampal CA1 neurones. Brain Res. Dev. 1996;91:29–40
  3. Deshpande LS, Nagarkatti N, Sombati S, Delorenzo RJ. The novel antiepileptic drug carisbamate (RWJ 333369) is effective in inhibiting spontaneous recurrent seizure discharges and blocking sustained repetitive firing in cultured hippocampal neurons. Epilepsy Res. 2008;79:158–165
  4. Deshpande, L.S., Nagarkatti, N., Ziobro, J.M., Sombati, S., Delorenzo, R.J., in press. Carisbamate prevents the development and expression of spontaneous recurrent epileptiform discharges and is neuroprotective in cultured hippocampal neurons. Epilepsia.
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  6. Gordon D, Merrick D, Auld V, Dunn R, Goldin AL, Davidson N, et al. Tissue-specific expression of the RI and RII sodium channel subtypes. Proc. Natl. Acad. Sci. U.S.A. 1987;84:8682–8686
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  9. Köhling R. Voltage-gated sodium channels in epilepsy. Epilepsia. 2002;43:1278–1295
  10. Liu Y, Qin N, Reitz T, Wang Y, Flores CM. Inhibition of the rat brain sodium channel Nav1, 2 after prolonged exposure to gabapentin. Epilepsy Res. 2006;70:263–268
  11. Maletic-Savatic M, Lenn NJ, Trimmer JS. Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. J. Neurosci. 1995;15:3840–3851
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  15. Rogawski MA. Diverse mechanisms of antiepileptic drugs in the development pipeline. Epilepsy Res. 2006;69:273–294
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  17. White HS, Srivastava A, Klein B, Zhao B, Choi YM, Gordon R, et al. The novel investigational neuromodulator RWJ 333369 displays a broad-spectrum anticonvulsant profile in rodent seizure and epilepsy models. Epilepsia. 2006;47(Suppl. 4):200
  18. Yao C, Doose DR, Novak G, Bialer M. Pharmacokinetics of the new antiepileptic and CNS drug RWJ-333369 following single and multiple dosing to humans. Epilepsia. 2006;47:1822–1829

PII: S0920-1211(08)00277-5

doi: 10.1016/j.eplepsyres.2008.09.006

Epilepsy Research
Volume 83, Issue 1 , Pages 66-72 , January 2009

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