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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2020-02-26 21:40:31 UTC
HMDB IDHMDB0014878
Secondary Accession Numbers
  • HMDB14878
Metabolite Identification
Common NameRiluzole
DescriptionRiluzole, also known as rilutek, belongs to the class of organic compounds known as benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-membered ring with four carbon atoms, one nitrogen atom and one sulfur atom). Riluzole is a medication used to treat amyotrophic lateral sclerosis. 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. Riluzole is a drug which is used for the treatment of amyotrophic lateral sclerosis (als, lou gehrig's disease). A 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 now by Biohaven Pharmaceuticals. Riluzole is a strong basic compound (based on its pKa). CYP1A2 substrates, inhibitors and inducers would probably interact with riluzole, due its dependency on this cytochrome for metabolism. Riluzole is a potentially toxic compound. Very common (>10% frequency): nausea; weakness; decreased lung functionCommon (1–10% frequency): headache; dizziness; drowsiness; vomiting; abdominal pain; increased aminotransferasesUncommon (0.1-1% frequency): pancreatitis; interstitial lung diseaseRare (<0.1% frequency): neutropenia; allergic reaction (including angiooedema, anaphylactoid reaction)Symptoms of overdose include: neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma and methemoglobinemia. A Cochrane Library review states a 9% gain in the probability of surviving one year. 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.
Structure
Data?1582753231
Synonyms
ValueSource
RilutekKegg
Riluzole impax brandHMDB
2 Amino 6 trifluoromethoxybenzothiazoleHMDB
2-Amino-6-trifluoromethoxybenzothiazoleHMDB
Aventis brand OF riluzoleHMDB
Riluzole aventis brandHMDB
Impax brand OF riluzoleHMDB
Rhone-poulenc rorer brand OF riluzoleHMDB
Aventis behring brand OF riluzoleHMDB
Rhone poulenc rorer brand OF riluzoleHMDB
Chemical FormulaC8H5F3N2OS
Average Molecular Weight234.198
Monoisotopic Molecular Weight234.007468097
IUPAC Name6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
Traditional Nameriluzole
CAS Registry Number1744-22-5
SMILES
NC1=NC2=C(S1)C=C(OC(F)(F)F)C=C2
InChI Identifier
InChI=1S/C8H5F3N2OS/c9-8(10,11)14-4-1-2-5-6(3-4)15-7(12)13-5/h1-3H,(H2,12,13)
InChI KeyFTALBRSUTCGOEG-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-membered ring with four carbon atoms, one nitrogen atom and one sulfur atom).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazoles
Sub ClassNot Available
Direct ParentBenzothiazoles
Alternative Parents
Substituents
  • 1,3-benzothiazole
  • Benzenoid
  • 1,3-thiazol-2-amine
  • Azole
  • Thiazole
  • Heteroaromatic compound
  • Trihalomethane
  • Azacycle
  • Amine
  • Organopnictogen compound
  • Organic oxygen compound
  • Alkyl halide
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organic nitrogen compound
  • Alkyl fluoride
  • Hydrocarbon derivative
  • Halomethane
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Source

Route of exposure

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point119 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.04 g/LNot Available
LogP2.3Not Available
Experimental Spectral PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.04 g/LALOGPS
logP10(2.83) g/LALOGPS
logP10(3.4) g/LChemAxon
logS10(-3.8) g/LALOGPS
pKa (Strongest Acidic)16.44ChemAxon
pKa (Strongest Basic)4.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area48.14 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity44.37 m³·mol⁻¹ChemAxon
Polarizability18.59 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Predicted Kovats Retention Indices

Not Available
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Riluzole GC-MS (Non-derivatized) - 70eV, Positivesplash10-00li-2940000000-00c484cbc92e6a94bae02017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Riluzole GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Riluzole GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Riluzole , positive-QTOFsplash10-000i-2590000000-5a9d0f7cdad7e4f2ec6b2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Riluzole , positive-QTOFsplash10-000i-0390000000-4bd44ae3d25f047943e82017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Riluzole , positive-QTOFsplash10-000i-3940000000-1da38288b84e863a64e52017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Riluzole 35V, Positive-QTOFsplash10-000i-0590000000-79d300cfd2b43692d9632021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Riluzole 35V, Negative-QTOFsplash10-001i-0190000000-63069bec4e00478eb3802021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 10V, Positive-QTOFsplash10-000i-0190000000-f0b481a2910122ad9bdc2016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 20V, Positive-QTOFsplash10-000i-0090000000-d6a855ead1f5f5fe1a372016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 40V, Positive-QTOFsplash10-014i-0900000000-b797bc65c275796519492016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 10V, Negative-QTOFsplash10-001i-0090000000-4caa5c429c103b56c1512016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 20V, Negative-QTOFsplash10-001i-0090000000-78bd33541d87ef6453032016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 40V, Negative-QTOFsplash10-03di-0900000000-6f96de4ddfa58b872d2e2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 10V, Positive-QTOFsplash10-000i-0090000000-77cd58803ff632c890022021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 20V, Positive-QTOFsplash10-000i-0090000000-77cd58803ff632c890022021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 40V, Positive-QTOFsplash10-0a4r-0490000000-ab117c07a1f16bb2d5f82021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 10V, Negative-QTOFsplash10-001i-0090000000-9f868134c3a763fd526e2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 20V, Negative-QTOFsplash10-001i-0090000000-9f868134c3a763fd526e2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Riluzole 40V, Negative-QTOFsplash10-0a4i-9320000000-2312256d22d9ca57d0142021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00740 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00740 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00740
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4892
KEGG Compound IDC07937
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRiluzole
METLIN IDNot Available
PubChem Compound5070
PDB IDNot Available
ChEBI ID138898
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T: Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. 1997 Aug;282(2):707-14. [PubMed:9262334 ]
  2. Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK: An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. [PubMed:14702270 ]
  3. van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ: Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol. 2005 Mar;59(3):310-3. [PubMed:15752377 ]
  4. Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH: Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. [PubMed:15993857 ]
  5. Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. doi: 10.1038/sj.npp.1301652. Epub 2008 Jan 2. [PubMed:18172433 ]
  6. Lamanauskas N, Nistri A: Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro. Eur J Neurosci. 2008 May;27(10):2501-14. doi: 10.1111/j.1460-9568.2008.06211.x. Epub 2008 Apr 26. [PubMed:18445055 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular weight:
58164.815
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in transport
Specific function:
Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate.
Gene Name:
SLC7A11
Uniprot ID:
Q9UPY5
Molecular weight:
55422.44
References
  1. Wokke J: Riluzole. Lancet. 1996 Sep 21;348(9030):795-9. [PubMed:8813989 ]
  2. Azbill RD, Mu X, Springer JE: Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res. 2000 Jul 21;871(2):175-80. [PubMed:10899284 ]
  3. 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. J Neurosci. 2003 Mar 1;23(5):1688-96. [PubMed:12629173 ]
  4. Gosselin RD, O'Connor RM, Tramullas M, Julio-Pieper M, Dinan TG, Cryan JF: Riluzole normalizes early-life stress-induced visceral hypersensitivity in rats: role of spinal glutamate reuptake mechanisms. Gastroenterology. 2010 Jun;138(7):2418-25. doi: 10.1053/j.gastro.2010.03.003. Epub 2010 Mar 10. [PubMed:20226190 ]
  5. Hayashida K, Parker RA, Eisenach JC: Activation of glutamate transporters in the locus coeruleus paradoxically activates descending inhibition in rats. Brain Res. 2010 Mar 4;1317:80-6. doi: 10.1016/j.brainres.2009.12.086. Epub 2010 Jan 6. [PubMed:20059984 ]
General function:
Involved in ion channel activity
Specific function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular weight:
226937.5
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Schwartz G, Fehlings MG: Secondary injury mechanisms of spinal cord trauma: a novel therapeutic approach for the management of secondary pathophysiology with the sodium channel blocker riluzole. Prog Brain Res. 2002;137:177-90. [PubMed:12440368 ]
  4. Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T: Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. 1997 Aug;282(2):707-14. [PubMed:9262334 ]
  5. Weiss S, Benoist D, White E, Teng W, Saint DA: Riluzole protects against cardiac ischaemia and reperfusion damage via block of the persistent sodium current. Br J Pharmacol. 2010 Jul;160(5):1072-82. doi: 10.1111/j.1476-5381.2010.00766.x. [PubMed:20590601 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular weight:
72313.5
References
  1. Milane A, Vautier S, Chacun H, Meininger V, Bensimon G, Farinotti R, Fernandez C: Interactions between riluzole and ABCG2/BCRP transporter. Neurosci Lett. 2009 Mar 6;452(1):12-6. doi: 10.1016/j.neulet.2008.12.061. Epub 2009 Jan 6. [PubMed:19146924 ]