Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis

J Neurol. 2009 Jan;256(1):89-103. doi: 10.1007/s00415-009-0075-3. Epub 2009 Jan 24.


Teriflunomide is an orally available anti-inflammatory drug that prevents T and B cell proliferation and function by inhibition of dihydroorotate dehydrogenase. It is currently being developed for the treatment of multiple sclerosis (MS). We report here for the first time the anti-inflammatory effects of teriflunomide in the Dark Agouti rat model of experimental autoimmune encephalomyelitis (EAE). Neurological evaluation demonstrated that prophylactic dosing of teriflunomide at 3 and 10 mg/kg delayed disease onset and reduced maximal and cumulative scores. Therapeutic administration of teriflunomide at doses of 3 or 10 mg/kg at disease onset significantly reduced maximal and cumulative disease scores as compared to vehicle treated rats. Dosing teriflunomide at disease remission, at 3 and 10 mg/kg, reduced the cumulative scores for the remaining course of the disease. Teriflunomide at 10 mg/kg significantly reduced inflammation, demyelination, and axonal loss when dosed prophylactically or therapeutically. In electrophysiological somatosensory evoked potential studies, therapeutic administration of teriflunomide, at the onset of disease, prevented both a decrease in waveform amplitude and an increase in the latency to waveform initiation in EAE animals compared to vehicle. Therapeutic dosing with teriflunomide at disease remission prevented a decrease in evoked potential amplitude, prevented an increase in latency, and enhanced recovery time within the CNS.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Axons / drug effects*
  • Axons / pathology
  • Behavior, Animal*
  • Central Nervous System Agents / administration & dosage
  • Central Nervous System Agents / pharmacology*
  • Crotonates / administration & dosage
  • Crotonates / pharmacology*
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / etiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / psychology
  • Evoked Potentials, Somatosensory / drug effects*
  • Hydroxybutyrates
  • Male
  • Nitriles
  • Rats
  • Toluidines / administration & dosage
  • Toluidines / pharmacology*
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Central Nervous System Agents
  • Crotonates
  • Hydroxybutyrates
  • Nitriles
  • Toluidines
  • teriflunomide