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 ability to stimulate glutamate uptake seems to mediate many of its effects.
In vitro, riluzole protects cultured neurons from anoxic damage, from the toxic effects of glutamic-acid-uptake inhibitors, and from the toxic factor in the CSF of patients with amyotrophic lateral sclerosis.
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 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.
^Miller RG, Mitchell JD, Lyon M, Moore DH (2007). "Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)". In Miller, Robert G. Cochrane Database Syst Rev (1): CD001447. doi:10.1002/14651858.CD001447.pub2. PMID17253460.
^Coric V, Taskiran S, Pittenger C, et al. currently a study is underway at the NIH in Bethesda using riluzol for the treatment of OCD by Dr Grant (September 2005). "Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial". Biol Psychiatry58 (5): 424–8. doi:10.1016/j.biopsych.2005.04.043. PMID15993857.
^Mathew SJ, Amiel JM, Coplan JD, Fitterling HA, Sackeim HA, Gorman JM (December 2005). "Open-label trial of riluzole in generalized anxiety disorder". Am J Psychiatry162 (12): 2379–81. doi:10.1176/appi.ajp.162.12.2379. PMID16330605.