There has been some evidence to show that higher doses might produce more significant improvements in ALS patients but at almost £6 (US$10) per tablet it is at risk of being prohibitively expensive given the modest benefit to patients. One study in the Netherlands found that riluzole is metabolized 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.
Contraindications for riluzole include: known prior hypersensitivity to riluzole or any of the excipients inside the preparations, hepatic disease and pregnancy or lactation.
CYP1A2 substrates, inhibitors and inducers would probably interact with riluzole, due its dependency on this cytochrome for metabolism.
Symptoms of overdose include: neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma and methaemoglobinaemia. Severe methaemoglobinaemia may be rapidly reversible after treatment with methylene blue.
Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. 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 addition to its role in accelerating glutamate clearance from the synapse, Riluzole may also prevent glutamate release from presynaptic terminals. These effects combined could significantly reduce glutamate signaling and cause indirect antagonism without acting at glutamate receptors themselves.
^Zarate CA, Jr; Payne, JL; Quiroz, J; Sporn, J; Denicoff, KK; Luckenbaugh, D; Charney, DS; Manji, HK (January 2004). "An open-label trial of riluzole in patients with treatment-resistant major depression.". The American Journal of Psychiatry161 (1): 171–4. doi:10.1176/appi.ajp.161.1.171. PMID14702270.Cite uses deprecated parameters (help)
^Bellingham, MC (February 2011). "A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade?". CNS Neuroscience & Therapeutics17 (1): 4–31. doi:10.1111/j.1755-5949.2009.00116.x. PMID20236142.