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Riluzole is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase survival by approximately two months.
It is marketed by Aventis Pharmaceuticals Inc with the brand name Rilutek.
Mechanism of action
Riluzole has several actions:
Riluzole preferentially blocks TTX-S sodium channels, which are associated with damaged neurons (Song et al 1997). 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.
Studies of efficacy
A 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 (Miller RG et al 2005). 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 50mg 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 (van Kan et al 2005).
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 (Zarate et al 2004) and as an anxiolytic in Obsessive-compulsive disorder (Coric et al 2005) and in GAD (Mathew et al 2005).
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Riluzole". A list of authors is available in Wikipedia.|