|Trade names||Rilutek, Tiglutik, Exservan, others|
|Main uses||Amyotrophic lateral sclerosis|
|Side effects||Weakness, liver problems|
|Elimination half-life||9–15 hours|
|Chemical and physical data|
|Molar mass||234.20 g·mol−1|
|3D model (JSmol)|
Riluzole, sold under the brand name Rilutek among others, is a medication used to treat amyotrophic lateral sclerosis. It delays the need for a ventilator or tracheostomy and improves survival by two to three months. It is taken by mouth, either as a tablet or liquid.
Common side effects include weakness and liver problems. Other side effects may include anaphylaxis, interstitial lung disease, and low neutrophils. How it works is unclear, but may be due to a decrease in glutamate in the nervous system.
Riluzole was approved for medical use in the United States in 1995 and Europe in 1996. It is available as a generic medication. In the United Kingdom 4 weeks costs the NHS about £23 as of 2021. This amount in the United States is about 33 USD.
Amyotrophic lateral sclerosis
Riluzole was approved in the United States for the treatment of ALS by the U.S. Food and Drug Administration (FDA) in 1995. A Cochrane Library review states a 9% gain in the probability of surviving one year.
It is taken at a dose of 50 mg twice per day.
- Very common (>10% frequency): nausea; weakness; decreased lung function
- Common (1–10% frequency): headache; dizziness; drowsiness; vomiting; abdominal pain; increased aminotransferases
- Uncommon (0.1-1% frequency): pancreatitis; interstitial lung disease
- Rare (<0.1% frequency): neutropenia; allergic reaction (including angiooedema, anaphylactoid reaction)
Symptoms of overdose include: neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma and methemoglobinemia. Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue.
Contraindications for riluzole include: known prior hypersensitivity to riluzole or any of the excipients inside the preparations, liver disease, pregnancy or lactation.
Mechanism of action
Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. Riluzole has also been reported to directly inhibit the kainate and NMDA receptors. The drug has also been shown to postsynaptically potentiate GABAA receptors via an allosteric binding site. However, the action of riluzole on glutamate receptors has been controversial, as no binding of the drug to any known sites has been shown for them. In addition, as its antiglutamatergic action is still detectable in the presence of sodium channel blockers, it is also uncertain whether or not it acts via this way. Rather, its ability to stimulate glutamate uptake seems to mediate many of its effects. In addition to its role in accelerating glutamate clearance from the synapse, riluzole may also prevent glutamate release from presynaptic terminals. Since CK1δ plays a key role in TDP-43 proteinopathy, a pathological hallmark of ALS, this could help to better decipher drug mechanism of action.
Society and culture
Riluzole was approved for medical use in the European Union in October 1996.
A reformulation of riluzole that originated at Yale University and is known by the code name BHV-0223 is under development[when?] for the treatment of generalized anxiety disorder and mood disorders by Biohaven Pharmaceuticals.
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