Archives of Pharmacal Research

, Volume 33, Issue 10, pp 1567–1574

Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (Fingolimod) in multiple sclerosis



FTY720 (fingolimod, Novartis) is a promising investigational drug for relapsing forms of multiple sclerosis (MS), an autoimmune and neurodegenerative disorder of the central nervous system. It is currently under FDA review in the United States, and could represent the first approved oral treatment for MS. Extensive, ongoing clinical trials in Phase II/III have supported both the efficacy and safety of FTY720. FTY720 itself is not bioactive, but when phosphorylated (FTY720-P) by sphingosine kinase 2, it becomes active through modulation of 4 of the 5 known G protein-coupled sphingosine 1-phosphate (S1P) receptors. The mechanism of action (MOA) is thought to be immunological, where FTY720 alters lymphocyte trafficking via S1P1. However, MOA for FTY720 in MS may also involve a direct, neurological action within the central nervous system in view of documented S1P receptor-mediated signaling influences in the brain, and this review considers observations that support an emerging neurological MOA.

Key words

FTY720 Fingolimod Sphingosine 1-phosphate receptors Multiple sclerosis Central nervous system 


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Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2010

Authors and Affiliations

  1. 1.Department of Molecular Biology, Dorris Neuroscience CenterThe Scripps Research InstituteLa JollaUSA
  2. 2.Department of Pharmacology, Division of Basic Medicine and ScienceGachon University of Medicine and ScienceIncheonKorea

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