Name: Riluzole
Synonyms: Rilutek®, RP 54274
Chemical Name: 6-trifluoromethoxy-2-benzothiazolamine
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline), Other (timeline)
Condition(s): Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2), Parkinson's Disease (Discontinued), Amyotrophic Lateral Sclerosis (Approved), Huntington's Disease (Discontinued)
Company: Sanofi
Approved for: Amyotrophic Lateral Sclerosis in many countries


Riluzole is the first FDA-approved medication for amyotrophic lateral sclerosis. It has been marketed in dozens of countries around the world since the late 1990s, and generic versions became available in the U.S. in 2013. Adverse events include blurred vision, difficulty breathing, weakness, dizziness, gastrointestinal discomfort, and others (see Mayo Clinic Drug Information).

Riluzole's mechanism of action is not fully understood, but it has been shown repeatedly to modulate glutamate neurotransmission by inhibiting both glutamate release and postsynatpic glutamate receptor signaling. It also has been reported to inhibit voltage-gated sodium channels and to be neuroprotective by suppressing astrocytosis (Martin et al., 1993, Hubert et al., 1994, Carbone et al. 2012).


Riluzole was approved for ALS because in several clinical trials it modestly extended survival or time to insertion of a breathing tube. Initial clinical trial reports of a slowing of muscle deterioration or symptomatic benefits were not corroborated in subsequent studies (see Bensimon et al., 1994Lacomblez et al 1996). Pharmacoeconomics research has challenged the cost-effectiveness of riluzole treatment of ALS (Messori et al., 1999).

Riluzole completed Phase 3 clinical trials for the treatment of both Parkinson's and Huntington's diseases. Both programs had negative results and were discontinued (Bensimon et al., 2009Landwehrmeyer et al., 2007).

Because glutamate-mediated excitotoxicity has been implicated in Alzheimer's disease, a rationale is seen to evaluate whether riluzole can slow neuronal loss and cognitive dysfunction in this disease. Starting in April 2013, a Phase 2, six-month, investigator-initated trial at Rockefeller Univeristy started testing riluzole in 48 patients with mild Alzheimer's who were already taking the cholinesterase inhibitor donepezil. Expected to run until 2017, this study will assess changes in cognitive function, changes in brain concentration of the neuronal viability marker N-acetylaspartate (NAA) as measured by magnetic resonance spectroscopy (MRS), and changes in brain glucose metabolism as measured by FDG-PET. Twenty-four patients will receive riluzole, and 24 will receive placebo tablets made at the Rockefeller University pharmacy.

In addition, riluzole has been, or is being, investigated for a variety of neurologic and neuropsychiatric conditions in various investigator-initiated academic trials. These include autism, ataxia, Fragile X, multiple sclerosis, spinal cord injury, depression and bipolar disease, obsessive-compulsive disorder, spinal muscular atrophy, and others. Riluzole is also being tested against melanoma and other forms of cancer.

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031
Rockefeller University NCT01703117


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Paper Citations

  1. . A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994 Mar 3;330(9):585-91. PubMed.
  2. . Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet. 1996 May 25;347(9013):1425-31. PubMed.
  3. . Cost effectiveness of riluzole in amyotrophic lateral sclerosis. Italian Cooperative Group for the Study of Meta-Analysis and the Osservatorio SIFO sui Farmaci. Pharmacoeconomics. 1999 Aug;16(2):153-63. PubMed.
  4. . Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain. 2009 Jan;132(Pt 1):156-71. Epub 2008 Nov 23 PubMed.
  5. . Riluzole in Huntington's disease: a 3-year, randomized controlled study. Ann Neurol. 2007 Sep;62(3):262-72. PubMed.
  6. . The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1. Eur J Pharmacol. 1993 Dec 21;250(3):473-6. PubMed.
  7. . Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat cultured granule cells: evidence for a dual mechanism of action. Br J Pharmacol. 1994 Sep;113(1):261-7. PubMed.
  8. . Riluzole neuroprotection in a Parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation. BMC Neurosci. 2012 Apr 5;13:38. PubMed.

External Citations

  1. Mayo Clinic Drug Information

Further Reading


  1. . An analysis of extended survival in patients with amyotrophic lateral sclerosis treated with riluzole. Arch Neurol. 1998 Apr;55(4):526-8. PubMed.
  2. . Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review. CNS Drug Rev. 2002;8(1):1-30. PubMed.
  3. . Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain. 2009 Jan;132(Pt 1):156-71. Epub 2008 Nov 23 PubMed.
  4. . Double-blind, placebo-controlled study to assess safety and efficacy of riluzole as a neuroprotective drug in patients with early, untreated Parkinson's disease. Neurology. 52 (Suppl. 2): 214-215, 12 Apr 1999. USA