Riluzole is an FDA approved drug used to slow the progress of Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease). The drug may delay the onset of ventilator-dependence or tracheostomy (breathing tube) in selected patients and may increase survival by approximately 3–5 months, but it is not a cure for ALS. It is marketed by Sanofi-Aventis with the brand name Rilutek.
Riluzole, preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced.
However, the action of riluzole on glutamate receptors has been controversial, as no binding of the molecule has been shown on any known receptor. In addition, as its antiglutamate 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 potent glutamate uptake activator activity seems to mediate many of its effects.
Cochrane Library review states a 9% gain in the probability of surviving one year. In secondary analyses of survival at separate time points, there was a significant survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. There were no data on quality of life, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients.
While riluzole has been proven to slow down ALS, patients do not report any subjective improvement. Approximately 10% of patients experience side effects such as nausea and fatigue which lead them to discontinue treatment. Safety monitoring includes regular liver function tests and people with liver disease such as hepatitis should be monitored especially carefully.
In the UK riluzole has been available through the NHS since 1997 at a standard dosage of 50 mg twice daily. There has been some evidence to show that higher doses might produce more significant improvements in ALS patients but at £5 a tablet it is at risk of being prohibitively expensive given the modest benefit to patients. One study in the Netherlands found that riluzole is metabolised differently by males and females, and its levels in plasma are decreased in patients who smoke cigarettes or take omeprazole.
A number of recent case studies have also indicated that riluzole may have clinical use in mood and anxiety disorders. It has been shown to have antidepressant properties in the treatment of refractory depression and as an anxiolytic in obsessive-compulsive disorder and in GAD.