Riluzole

Overview

Riluzole is a medication used to treat amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is available in tablet and liquid form. A thin film version of riluzole which dissolves on the tongue (commercially known as Exservan or Emylif) is available in the United States and United Kingdom.[1][2] WP

Uses, dosage and effects

Amyotrophic lateral sclerosis

Riluzole was approved in the United States for the treatment of ALS by the US Food and Drug Administration (FDA) in 1995. In 1996, riluzole was approved for use in treating ALS by the European Medicines Agency (EMA). A Cochrane Library review states a 9% gain in the probability of surviving one year.[1][2][3] WP

Risks and side effects

Contraindications

Contraindications for riluzole include: known prior hypersensitivity to riluzole or any of the excipients inside the preparations, liver disease, pregnancy or lactation.[4] WP

Adverse effects

• Very common (>10% frequency): nausea; weakness; decreased lung function[5] WP
• Common (1–10% frequency): headache; dizziness; drowsiness; vomiting; abdominal pain; increased aminotransferases[6] WP
• Uncommon (0.1–1% frequency): pancreatitis; interstitial lung disease[6] WP
• Rare (<0.1% frequency): neutropenia; allergic reaction (including angiooedema, anaphylactoid reaction)[6] WP

Overdose

Symptoms of overdose include: neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma and methemoglobinemia. Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue.[4] WP

Interactions

Interactions

CYP1A2 substrates, inhibitors and inducers would probably interact with riluzole, due to its dependency on this cytochrome for metabolism.[4] WP

Pharmacology

Mechanism of action

Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. Riluzole has also been reported to directly inhibit the kainate and NMDA receptors. The drug has also been shown to postsynaptically potentiate GABAA receptors via an allosteric binding site. However, the action of riluzole on glutamate receptors has been controversial, as no binding of the drug to any known sites has been shown for them. In addition, as its antiglutamatergic 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.[7–15] WP

Research

Research

A number of case studies and randomized controlled trials have indicated that riluzole, which is neuroprotective and a glutamate modulator, may have use in mood and anxiety disorders. Riluzole is thought to have "neuroprotective" properties mainly owing to its ability to modulate glutamate release. However, it failed in trials of Huntington's disease and Parkinson's disease. A 2024 study comparing the effects of riluzole in patients with traumatic spinal cord injury to a control group found riluzole treated patients had higher American Spinal Injury Association (ASIA) motor scores and lower mortality rates at 3 months, though the scores were not statistically significant.[16–20] WP

Riluzole has been investigated in rodent models for its potential ability to protect against noise-induced hearing loss (NIHL) and cisplatin-induced ototoxicity. These protective effects are believed to be caused by riluzole's antioxidant and anti-apoptotic properties, but other mechanisms, including modulation of glutamate signaling, are also being investigated. However, further research, especially in human trials, is necessary to confirm these findings and establish riluzole's clinical efficacy for treating hearing loss.[21][22] WP

A sublingual reformulation of riluzole that originated at Yale University and is known by the code name BHV-0223 is under development for the treatment of generalized anxiety disorder and mood disorders by Biohaven Pharmaceuticals. A prodrug formulation of riluzole, troriluzole, has been researched as a potential treatment for several different conditions.[23–27] WP⚠ Wikipedia itself has flagged this text: when?.

Legal status

Legal status

Riluzole was approved for medical use in the European Union in October 1996.[28] WP

Chemistry

Formula

C8H5F3N2OS PC

CAS number

1744-22-5 PC

Molar mass (g/mol)

234.20 PC

IUPAC name (computed by PubChem)

6-(trifluoromethoxy)-1,3-benzothiazol-2-amine PC

SMILES

C1=CC2=C(C=C1OC(F)(F)F)SC(=N2)N PC

InChIKey

FTALBRSUTCGOEG-UHFFFAOYSA-N PC

PubChem CID

5070

IUPAC name

6-(trifluoromethoxy)benzothiazol-2-amine WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). The Cochrane Database of Systematic Reviews. March 2012. doi:10.1002/14651858.CD001447.pub3 · PMID 22419278 · PMC7055506
2. Other Riluzole/Tiglutik
3. Journal / agency LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. May 2018. PMID 31644225
4. Other PRODUCT INFORMATION RILUTEK® (riluzole) Tablets. January 6, 2009
5. Other Rilutek (riluzole) dosing, indications, interactions, adverse effects, and more
6. Other Australian Medicines Handbook. 2013
7. Journal / agency Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T. Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. The Journal of Pharmacology and Experimental Therapeutics. August 1997. doi:10.1016/S0022-3565(24)36856-9 · PMID 9262334
8. Journal / agency Bellingham MC. 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 & Therapeutics. February 2011. doi:10.1111/j.1755-5949.2009.00116.x · PMID 20236142 · PMC6493865
9. Journal / agency Debono MW, Le Guern J, Canton T, Doble A, Pradier L. Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes. European Journal of Pharmacology. April 1993. doi:10.1016/0014-2999(93)90147-a · PMID 7685290
10. Journal / agency He Y, Benz A, Fu T, Wang M, Covey DF, Zorumski CF, Mennerick S. Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function. Neuropharmacology. February 2002. doi:10.1016/s0028-3908(01)00175-7 · PMID 11804616
11. Journal / agency Wokke J. Riluzole. Lancet. September 1996. doi:10.1016/S0140-6736(96)03181-9 · PMID 8813989
12. Journal / agency Kretschmer BD, Kratzer U, Schmidt WJ. Riluzole, a glutamate release inhibitor, and motor behavior. Naunyn-Schmiedeberg's Archives of Pharmacology. August 1998. doi:10.1007/pl00005241 · PMID 9750003
13. Journal / agency Azbill RD, Mu X, Springer JE. Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Research. July 2000. doi:10.1016/S0006-8993(00)02430-6 · PMID 10899284
14. Journal / agency Dunlop J, Beal McIlvain H, She Y, Howland DS. Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis. The Journal of Neuroscience. March 2003. doi:10.1523/JNEUROSCI.23-05-01688.2003 · PMID 12629173 · PMC6741992
15. Journal / agency Wang SJ, Wang KY, Wang WC. Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Neuroscience. January 2004. doi:10.1016/j.neuroscience.2004.01.019 · PMID 15051158
16. Journal / agency Kawashima Y, Yamada M, Furuie H, Kuniishi H, Akagi K, Kawashima T, Noda T, Yamada M. Effects of riluzole on psychiatric disorders with anxiety or fear as primary symptoms: A systematic review. Neuropsychopharmacology Reports. September 2023. doi:10.1002/npr2.12364 · PMID 37463744 · PMC10496048
17. Journal / agency Grant P, Song JY, Swedo SE. Review of the use of the glutamate antagonist riluzole in psychiatric disorders and a description of recent use in childhood obsessive-compulsive disorder. Journal of Child and Adolescent Psychopharmacology. August 2010. doi:10.1089/cap.2010.0009 · PMID 20807069 · PMC2958461
18. Journal / agency Zarate CA, Manji HK. Riluzole in psychiatry: a systematic review of the literature. Expert Opinion on Drug Metabolism & Toxicology. September 2008. doi:10.1517/17425255.4.9.1223 · PMID 18721116 · PMC2587133
19. Journal / agency Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs. 2008. doi:10.2165/00023210-200822090-00004 · PMID 18698875
20. Journal / agency Weisbrod LJ, Nilles-Melchert TT, Bergjord JR, Surdell DL. Safety and Efficacy of Riluzole in Traumatic Spinal Cord Injury: A Systematic Review With Meta-Analyses. Neurotrauma Reports. November 2024. doi:10.1089/neur.2023.0114 · PMID 38414779 · PMC10898229
21. Journal / agency Üstün Bezgin S, Uygur KK, Gökdoğan Ç, Elmas Ç, Göktaş G. The Effects of Riluzole on Cisplatin-induced Ototoxicity. International Archives of Otorhinolaryngology. July 2019. doi:10.1055/s-0038-1676654 · PMID 31360245 · PMC6660296
22. Journal / agency Ruel J, Wang J, Pujol R, Hameg A, Dib M, Puel JL. Neuroprotective effect of riluzole in acute noise-induced hearing loss. NeuroReport. July 2005. doi:10.1097/00001756-200507130-00011 · PMID 15973153
23. Journal / agency BHV 0223 – AdisInsight
24. Journal / agency Harris E. Industry update: the latest developments in therapeutic delivery. Therapeutic Delivery. 2015. doi:10.4155/tde.15.44
25. Other Terry M. Biohaven Reports Positive Early Clinical Trial Results for Anxiety Drug. August 16, 2018
26. Journal / agency van Roessel PJ, Grassi G, Aboujaoude EN, Menchón JM, Van Ameringen M, Rodríguez CI. Treatment-resistant OCD: Pharmacotherapies in adults. Comprehensive Psychiatry. January 2023. doi:10.1016/j.comppsych.2022.152352 · PMID 36368186
27. Journal / agency Silk AW, Saraiya B, Groisberg R, Chan N, Spencer K, Girda E, Shih W, Palmeri M, Saunders T, Berman RM, Coric V, Chen S, Zloza A, Vieth J, Mehnert JM, Malhotra J. A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors. European Journal of Medical Research. July 2022. doi:10.1186/s40001-022-00732-w · PMID 35780243 · PMC9250196
28. Journal / agency Rilutek EPAR. April 16, 2007

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