riluzole indications/contra

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

Drug dosage:

DoseUnitRoute
0.10 g O

Approvals:

DateAgencyCompanyOrphan
Dec. 12, 1995 FDA COVIS PHARMA SARL

FDA Adverse Event Reporting System

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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
Disease progression 96.68 40.45 29 257 32230 3353343
Amyotrophic lateral sclerosis 78.97 40.45 12 274 485 3385088
Death 73.63 40.45 36 250 152288 3233285
Pyrexia 50.53 40.45 23 263 81092 3304481

Pharmacologic Action:

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SourceCodeDescription
ATC N07XX02 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
OTHER NERVOUS SYSTEM DRUGS
Other nervous system drugs
MeSH PA D000927 Anticonvulsants
MeSH PA D002491 Central Nervous System Agents
MeSH PA D018683 Excitatory Amino Acid Agents
MeSH PA D018691 Excitatory Amino Acid Antagonists
MeSH PA D018696 Neuroprotective Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D020011 Protective Agents
FDA EPC N0000175740 Benzothiazole
FDA Chemical/Ingredient N0000167094 Benzothiazoles

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Amyotrophic lateral sclerosis indication 86044005 DOID:332
Alcoholism contraindication 7200002
Hyperbilirubinemia contraindication 14783006 DOID:2741
Jaundice contraindication 18165001
Interstitial pneumonia contraindication 64667001 DOID:3082
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

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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:

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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:

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IDSource
2326 IUPHAR_LIGAND_ID
4020941 VUID
N0000148421 NUI
C0073379 UMLSCUI
D00775 KEGG_DRUG
7LJ087RS6F UNII
5912 INN_ID
DB00740 DRUGBANK_ID
CHEMBL744 ChEMBL_ID
5070 PUBCHEM_CID
4020941 VANDF
N0000006860 NDFRT
N0000148421 NDFRT
005183 NDDF
35623 RXNORM
109141001 SNOMEDCT_US
386980005 SNOMEDCT_US
5425 MMSL
d03869 MMSL
162294 MMSL
CHEBI:8863 CHEBI
D019782 MESH_DESCRIPTOR_UI
657 PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Rilutek HUMAN PRESCRIPTION DRUG LABEL 1 0075-7700 TABLET, FILM COATED 50 mg ORAL NDA 12 sections
Rilutek HUMAN PRESCRIPTION DRUG LABEL 1 0179-0143 TABLET 50 mg ORAL NDA 11 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 0179-0150 TABLET, FILM COATED 50 mg ORAL ANDA 11 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 0179-0217 TABLET 50 mg ORAL ANDA 16 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 0378-4145 TABLET, FILM COATED 50 mg ORAL ANDA 16 sections
RILUZOLE HUMAN PRESCRIPTION DRUG LABEL 1 60505-3285 TABLET, FILM COATED 50 mg ORAL ANDA 16 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 62756-538 TABLET, FILM COATED 50 mg ORAL ANDA 16 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 64980-191 TABLET, FILM COATED 50 mg ORAL NDA authorized generic 16 sections
Riluzole HUMAN PRESCRIPTION DRUG LABEL 1 67877-286 TABLET 50 mg ORAL ANDA 16 sections
RILUZOLE HUMAN PRESCRIPTION DRUG LABEL 1 68084-908 TABLET, FILM COATED 50 mg ORAL ANDA 17 sections
riluzole HUMAN PRESCRIPTION DRUG LABEL 1 68462-381 TABLET, FILM COATED 50 mg ORAL ANDA 16 sections
Rilutek HUMAN PRESCRIPTION DRUG LABEL 1 70515-700 TABLET 50 mg ORAL NDA 16 sections