Fingolimod was first synthesized in the early 1990s as part of an extensive program of chemical derivatization of myriocin, with the goal of creating a novel immunosuppressant that would be more potent and less toxic in vivo. Fingolimod's mechanism of action in multiple sclerosis (MS) is not known with certainty. Fingolimod was initially developed to prevent allograt rejection after demonstration that it was effective in a variety of animal transplantation models, including kidney, heart, pancreatic islet cells and skin. Fingolimod was approved by the Food and Drug Administration (FDA) to reduce relapses and disability progression in relapsing forms of MS. Fingolimod's generally good safety profile and tolerability, including oral route of administration, make fingolimod an attractive treatment option for patients with relapsing forms of MS. Better delineation of the mechanisms leading to both the beneficial and adverse effects of fingolimod is necessary to develop more effective and better-tolerated compounds.

Cyclophosphamide is employed in autoimmune neuropathies, and vasculidities such as Wegener's granulomatosis and polyarteritis nodosa. Mycophenolate mofetil (Cellcept) is a potent immunosuppressant and has been used increasingly in post-transplant patients because it is considered less toxic than azathioprine and cyclophosphamide. Methotrexate is a general immunosuppressant that acts primarily by inhibition of dihydrofolate reductase. Azathioprine (Imuran) is a purine analog that is metabolized to 6-mercaptopurine and thioinosine acid, which compete with DNA nucleotides, causing immunosuppression. This chapter lists randomized trials of immunosuppressives in multiple sclerosis (MS). In the right patient, cyclophosphamide has been demonstrated effective, while work with methotrexate and mycophenolate mofetil has been less conclusive. Azathioprine also is likely to have a favorable effect on MS, and is relatively safe. Recent novel uses of immunosuppressives in active patients, or new disease populations have broadened the possible uses of these drugs.