Riluzole


Riluzole is a medication used to treat amyotrophic lateral sclerosis. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is available in tablet and liquid form.

Medical use

Amyotrophic lateral sclerosis

Riluzole was approved in the United States for the treatment of ALS by the FDA in 1995. A Cochrane Library review states a 9% gain in the probability of surviving one year.

Adverse effects

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

Contraindications for riluzole include: known prior hypersensitivity to riluzole or any of the excipients inside the preparations, liver disease, pregnancy or lactation.

Interactions

substrates, inhibitors and inducers would probably interact with riluzole, due its dependency on this cytochrome for metabolism.

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.

Synthesis

Riluzole can be prepared beginning with the reaction of 4-aniline with potassium thiocyanate followed by reaction with bromine, forming the thiazole ring.

Research

A number of recent case studies have indicated that riluzole may have use in mood and anxiety disorders.
A reformulation of riluzole that originated at Yale University and is known by the code name BHV-0223 is under development for the treatment of generalized anxiety disorder and mood disorders by Biohaven Pharmaceuticals.
Riluzole, which is neuroprotective and glutamate modulator could be used for psychiatric problems though it failed in trials of Huntington's disease and Parkinson's disease.