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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 (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., 1993Hubert et al., 1994Carbone et al., 2012).

Glutamate-mediated toxicity has been implicated in Alzheimer’s disease. In two AD mouse models, riluzole administration, either before or during amyloid accumulation, prevented memory decline (Okamoto et al., 2018; Hascup et al., 2021). Riluzole was reported to reduce tau pathology and improve memory performance in TauP301L-expressing mice (Hunsberger et al., 2015). In rats, riluzole appeared to prevent age-related changes in gene expression similar to those seen in AD (Pereira et al., 2016).


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 (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).

Starting in April 2013, a Phase 2, six-month, investigator-initiated trial at Rockefeller University started testing riluzole in 50 patients with mild Alzheimer's who were already taking the cholinesterase inhibitor donepezil. It assessed 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. According to published results, 26 patients received riluzole 50 mg twice daily, and 24 received placebo tablets made at the Rockefeller University pharmacy; 22 and 20 completed the study. In riluzole-treated patients, glucose metabolism declined significantly less in the posterior cingulate compared to those on placebo. Trends toward less decline were seen in other prespecified brain regions, as well. FDG-PET positively correlated with cognitive performance. No differences were found in NAA levels, but glutamate was increased at three and six months of treatment (Matthews et al., 2021).

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.

For details on clinical trials, see

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 2032 2033 2034
Rockefeller University NCT01703117

Last Updated: 02 Dec 2021


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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. . Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease. Brain. 2021 Jun 18; PubMed.
  7. . 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.
  8. . 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.
  9. . 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.
  10. . Riluzole reduces amyloid beta pathology, improves memory, and restores gene expression changes in a transgenic mouse model of early-onset Alzheimer's disease. Transl Psychiatry. 2018 Aug 14;8(1):153. PubMed.
  11. . Riluzole attenuates glutamatergic tone and cognitive decline in AβPP/PS1 mice. J Neurochem. 2021 Feb;156(4):513-523. Epub 2020 Nov 17 PubMed.
  12. . Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression. J Neurochem. 2015 Oct;135(2):381-94. Epub 2015 Aug 13 PubMed.
  13. . Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole. Mol Psychiatry. 2016 Mar 29; PubMed.

External Citations

  2. 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
  5. . Riluzole therapy in patients with Huntington's disease. Neurology. 50 (Suppl. 4): 72, Apr 1998
  6. . Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18733-8. Epub 2014 Dec 15 PubMed.