riluzole Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
2382 1744-22-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • riluzole
  • rilutek
  • rilutor
  • 6-Trifluoromethoxybenzothiazol-2-ylamine
  • riluzole hydrochloride
  • riluzole HCl
  • RP54274
  • RP-54274
The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective. The mode of action of riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release, 2) inactivation of voltage-dependent sodium channels, and 3) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors. Riluzole has also been shown, in a single study, to delay median time to death in a transgenic mouse model of ALS. These mice express human superoxide dismutase bearing one of the mutations found in one of the familial forms of human ALS. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. In in vitro tests, riluzole protected cultured rat motor neurons from the excitotoxic effects of glutamic acid and prevented the death of cortical neurons induced by anoxia. Due to its blockade of glutamatergic neurotransmission, riluzole also exhibits myorelaxant, sedative, and anticonvulsant properties.
  • Molecular weight: 234.20
  • Formula: C8H5F3N2OS
  • CLOGP: 3.23
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 48.14
  • ALOGS: -3.77
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability) 64 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 3.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 11.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.04 % Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 12, 1995 FDA COVIS PHARMA SARL

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Amyotrophic lateral sclerosis 104.90 37.31 17 566 1046 46684433
Death 72.43 37.31 47 536 335501 46349978

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Amyotrophic lateral sclerosis 133.24 32.90 23 750 993 29950712
Death 63.32 32.90 60 713 357223 29594482
Portal vein thrombosis 56.97 32.90 14 759 3450 29948255
Pancreatitis relapsing 37.16 32.90 7 766 490 29951215

Pharmacologic Action:

SourceCodeDescription
ATC N07XX02 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
OTHER NERVOUS SYSTEM DRUGS
Other nervous system drugs
FDA CS M0483511 Benzothiazoles
FDA EPC N0000175740 Benzothiazole
MeSH PA D000927 Anticonvulsants
MeSH PA D002491 Central Nervous System Agents
MeSH PA D018691 Excitatory Amino Acid Antagonists
MeSH PA D018696 Neuroprotective Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D020011 Protective Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Amyotrophic lateral sclerosis indication 86044005 DOID:332
Alcoholism contraindication 7200002
Hyperbilirubinemia contraindication 14783006 DOID:2741
Jaundice contraindication 18165001
Interstitial pneumonia contraindication 64667001
Liver function tests abnormal contraindication 166603001
Drug-induced hepatitis contraindication 235876009
Neutropenic disorder contraindication 303011007 DOID:1227
Fever greater than 100.4 Fahrenheit contraindication 426000000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.47 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium channel protein type 5 subunit alpha Ion channel BLOCKER WOMBAT-PK CHEMBL
Small conductance calcium-activated potassium channel protein 3 Ion channel ACTIVATOR EC50 4.90 IUPHAR
Sodium-dependent noradrenaline transporter Transporter Ki 5.76 DRUG MATRIX
Glutamate receptor ionotropic, NMDA 3A Ion channel WOMBAT-PK
Intermediate conductance calcium-activated potassium channel protein 4 Ion channel ACTIVATOR IC50 5.70 IUPHAR
Small conductance calcium-activated potassium channel protein 1 Ion channel ACTIVATOR EC50 4.68 IUPHAR
Pteridine reductase 1 Enzyme Ki 5.40 CHEMBL
Small conductance calcium-activated potassium channel protein 2 Unclassified ACTIVATOR EC50 4.89 IUPHAR

External reference:

IDSource
4020941 VUID
N0000148421 NUI
D00775 KEGG_DRUG
4020941 VANDF
C0678179 UMLSCUI
CHEBI:8863 CHEBI
657 PDB_CHEM_ID
CHEMBL744 ChEMBL_ID
D019782 MESH_DESCRIPTOR_UI
DB00740 DRUGBANK_ID
2326 IUPHAR_LIGAND_ID
5912 INN_ID
7LJ087RS6F UNII
5070 PUBCHEM_CID
196501 RXNORM
162294 MMSL
5067 MMSL
5425 MMSL
d03869 MMSL
005183 NDDF
109141001 SNOMEDCT_US
386980005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 0378-4145 TABLET, FILM COATED 50 mg ORAL ANDA 27 sections
EXSERVAN HUMAN PRESCRIPTION DRUG LABEL 1 10094-350 FILM 50 mg ORAL NDA 29 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 42291-775 TABLET, FILM COATED 50 mg ORAL ANDA 26 sections
RILUZOLE HUMAN PRESCRIPTION DRUG LABEL 1 60505-3285 TABLET, FILM COATED 50 mg ORAL ANDA 17 sections
Riluzole Human Prescription Drug Label 1 62756-538 TABLET, FILM COATED 50 mg ORAL ANDA 26 sections
Riluzole Human Prescription Drug Label 1 64980-191 TABLET, FILM COATED 50 mg ORAL NDA AUTHORIZED GENERIC 17 sections
Riluzole Human Prescription Drug Label 1 67877-286 TABLET 50 mg ORAL ANDA 26 sections
riluzole HUMAN PRESCRIPTION DRUG LABEL 1 68462-381 TABLET, FILM COATED 50 mg ORAL ANDA 26 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 69076-200 TABLET, FILM COATED 50 mg ORAL ANDA 26 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 69076-611 TABLET 50 mg ORAL ANDA 27 sections
Exservan HUMAN PRESCRIPTION DRUG LABEL 1 70510-2201 FILM 50 mg ORAL NDA 30 sections
Rilutek HUMAN PRESCRIPTION DRUG LABEL 1 70515-700 TABLET 50 mg ORAL NDA 27 sections
TIGLUTIK HUMAN PRESCRIPTION DRUG LABEL 1 70726-0303 LIQUID 50 mg ORAL NDA 31 sections