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Riluzole
Systematic (IUPAC) name
6-(trifluoromethoxy)benzothiazol-2-amine
Identifiers
CAS number 1744-22-5
ATC code N07XX02
PubChem 5070
DrugBank APRD00145
Chemical data
Formula C 8H5F3N2OS 
Mol. mass 234.199 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes  ?
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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 3–5 months.

It is marketed by sanofi-aventis with the brand name Rilutek.

Riluzole preferentially blocks TTX sensitive sodium channels, which are associated with damaged neurons.[1] 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.[2] 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.[3] [4]

Contents

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.[5] 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.

Clinical use

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.[6]

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[7] and as an anxiolytic in Obsessive-compulsive disorder[8] and in GAD.[9]

References

  1. ^ Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T (1 August 1997). "Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels". J Pharmacol Exp Ther. 282 (2): 707–14. PMID 9262334. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9262334.  
  2. ^ Wokke J (September 1996). "Riluzole". Lancet 348 (9030): 795–9. doi:10.1016/S0140-6736(96)03181-9. PMID 8813989.  
  3. ^ Azbill RD, Mu X, Springer JE (July 2000). "Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes". Brain Res. 871 (2): 175–80. doi:10.1016/S0006-8993(00)02430-6. PMID 10899284. http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(00)02430-6.  
  4. ^ Dunlop J, Beal McIlvain H, She Y, Howland DS (1 March 2003). "Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis". J Neurosci. 23 (5): 1688–96. PMID 12629173. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=12629173.  
  5. ^ Miller RG, Mitchell JD, Lyon M, Moore DH (2007). "Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)". Cochrane Database Syst Rev (1): CD001447. doi:10.1002/14651858.CD001447.pub2. PMID 17253460.  
  6. ^ van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ (March 2005). "Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis". Br J Clin Pharmacol 59 (3): 310–3. doi:10.1111/j.1365-2125.2004.02233.x. PMID 15752377.  
  7. ^ Zarate CA, Payne JL, Quiroz J, et al. (January 2004). "An open-label trial of riluzole in patients with treatment-resistant major depression". Am J Psychiatry 161 (1): 171–4. doi:10.1176/appi.ajp.161.1.171. PMID 14702270. http://ajp.psychiatryonline.org/cgi/content/full/161/1/171.  
  8. ^ 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 Psychiatry 58 (5): 424–8. doi:10.1016/j.biopsych.2005.04.043. PMID 15993857.  
  9. ^ 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 Psychiatry 162 (12): 2379–81. doi:10.1176/appi.ajp.162.12.2379. PMID 16330605.  

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