Axonal protection achieved in a model of multiple sclerosis using lamotrigine

J Neurol. 2006 Dec;253(12):1542-51. doi: 10.1007/s00415-006-0204-1.


Axonal degeneration is a major cause of permanent disability in multiple sclerosis (MS). Recent observations from our and other laboratories suggest that sodium accumulation within compromised axons is a key, early step in the degenerative process, and hence that limiting axonal sodium influx may represent a mechanism for axonal protection in MS. Here we assess whether lamotrigine, a sodium channel-blocking agent, is effective in preventing axonal degeneration in an animal model of MS, namely chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE). When administered from 7 days post-inoculation, lamotrigine provided a small but significant reduction in the neurological deficit present at the termination of the experiments (averaged over three independent experiments; vehicle: 3.5+/-2.7; lamotrigine: 2.6+/-2.0, P<0.05) and preserved more functional axons in the spinal cord (measured as mean compound action potential area; vehicle: 31.7; lamotrigine: 42.9+/-27.4, P<0.05). Histological examination of the thoracic spinal cord (n=71) revealed that lamotrigine treatment also provided significant protection against axonal degeneration (percentage degeneration in dorsal column; vehicle: 33.5 %+/-38.5; lamotrigine: 10.4 %+/-12.5, P<0.01). The findings suggest that lamotrigine may provide a novel avenue for axonal protection in MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Lamotrigine
  • Male
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / drug therapy
  • Nerve Degeneration / etiology*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control*
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology
  • Statistics, Nonparametric
  • Time Factors
  • Triazines / therapeutic use*


  • Neuroprotective Agents
  • Triazines
  • Lamotrigine