U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C8H5F3N2OS
Molecular Weight 234.1997
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RILUZOLE

SMILES

c1cc2c(cc1OC(F)(F)F)sc(=N)[nH]2

InChI

InChIKey=FTALBRSUTCGOEG-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including: https://www.drugs.com/mtm/riluzole.html http://www.rxlist.com/rilutek-drug.htm https://www.ncbi.nlm.nih.gov/pubmed/8813989

Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis. Its pharmacological properties include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release (activation of glutamate reuptake), 2) inactivation of voltage-dependent sodium channels, and 3) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors. Common adverse reactions include headache, abdominal pain, back pain, vomiting, dyspepsia, diarrhea, dizziness. Riluzole-treated patients that take other hepatotoxic drugs may be at increased risk for hepatotoxicity.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q12791|||Q5SQR9
Gene ID: 3778.0
Gene Symbol: KCNMA1
Target Organism: Homo sapiens (Human)
2.3 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RILUTEK

Approved Use

RILUTEK is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy.

Launch Date

8.1872637E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
359 ng/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RILUZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2257 ng × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RILUZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.8 h
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RILUZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4%
RILUZOLE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Disc. AE: Lung function decreased...
Other AEs: AST increased, Vomiting...
AEs leading to
discontinuation/dose reduction:
Lung function decreased (4%)
Other AEs:
AST increased (11.9%)
Vomiting (1%)
Abdominal pain (3%)
Dizziness (1%)
Asthenia (4%)
Malaise (2%)
Nausea (5%)
Sources: Page: p.1429
AEs

AEs

AESignificanceDosePopulation
Dizziness 1%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Vomiting 1%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
AST increased 11.9%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Malaise 2%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Abdominal pain 3%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Asthenia 4%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Lung function decreased 4%
Disc. AE
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
Nausea 5%
100 mg 2 times / day multiple, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.1429
unhealthy, ADULT
n = 244
Health Status: unhealthy
Condition: amyotrophic lateral sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 244
Sources: Page: p.1429
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
unlikely
unlikely
unlikely
unlikely
yes
yes
yes
likely (co-administration study)
Comment: Potential inhibitors of CYP1A2 (e.g. caffeine, phenacetin, theophylline, amitriphtyline, and quinolones) could decrease the rate of riluzole elimination, while inducers of CYP1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin, and omeprazole) could increase rate of riluzole elimination
Page: 8.0
yes
no (pharmacogenomic study)
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Acute hepatitis after riluzole administration.
1999 Mar
Riluzole for levodopa-induced dyskinesias in advanced Parkinson's disease.
1999 May 22
The clinical effectiveness and cost-effectiveness of riluzole for motor neurone disease: a rapid and systematic review.
2001
[Symptomatic treatment and palliative care of ALS].
2001
The pathogenesis of ALS: implications for treatment strategies.
2001
The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus-pituitary-adrenocortical system in elderly subjects.
2001
Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole.
2001 Apr
Amyotrophic lateral sclerosis associated with pregnancy.
2001 Dec
Differential cortico-motoneuron vulnerability after chronic mitochondrial inhibition in vitro and the role of glutamate receptors.
2001 Dec 20
Riluzole-induced acute pancreatitis.
2001 Jul
[Amyotrophic lateral sclerosis].
2001 Jul 27
Effect of the neuroprotective agent riluzole on intracellular Ca2+ levels in IMR32 neuroblastoma cells.
2001 Jun
Clinical trials in ALS: an overview.
2001 Jun
Pharmacological modulation of SK3 channels.
2001 Jun
A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group.
2001 Mar
Examining the evidence about treatment in ALS/MND.
2001 Mar
Slowing down ALS--is this good or bad?
2001 Mar
Clinical trials: the past, a lesson for the future.
2001 Mar
Interaction of the neuroprotective drug riluzole with GABA(A) and glycine receptor channels.
2001 Mar
Riluzole for motor neurone disease. Ambiguous diagnostic criteria mean that wide variations in elgibility may still persist.
2001 May 26
Riluzole reduces hyperactivity of subthalamic neurons induced by unilateral 6-OHDA lesion in the rat brain.
2001 Nov
Inter- and intraindividual variability of riluzole serum concentrations in patients with ALS.
2001 Oct 15
The cost utility analysis of riluzole for the treatment of amyotrophic lateral sclerosis in the UK.
2001 Oct 15
The Rilutek (riluzole) Global Early Access Programme: an open-label safety evaluation in the treatment of amyotrophic lateral sclerosis.
2001 Sep
Prognostic value of decremental responses to repetitive nerve stimulation in ALS patients.
2001 Sep 11
Any placebo controlled trial of riluzole would surely be unethical now.
2001 Sep 8
Riluzole for motor neurone disease. Reply from chairman of appraisal committee at NICE.
2001 Sep 8
Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).
2002
A fair innings for NICE?
2002
Workshop on primary progressive multiple sclerosis: meeting summary.
2002 Apr
Emerging strategies for drug development in motor neuron disease.
2002 Apr
Contribution of presynaptic Na(+) channel inactivation to paired-pulse synaptic depression in cultured hippocampal neurons.
2002 Feb
Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function.
2002 Feb
Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons.
2002 Jul 2
Early symptom progression rate is related to ALS outcome: a prospective population-based study.
2002 Jul 9
A comparison of the anti-nociceptive effects of voltage-activated Na+ channel blockers in the formalin test.
2002 Jun 12
Long-term safety of riluzole in amyotrophic lateral sclerosis.
2002 Mar
How useful are retrospective studies in evaluating therapeutic interventions?
2002 Mar
A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson's disease.
2002 Mar
Is glutamate involved in transient lower esophageal sphincter relaxations?
2002 Mar
Riluzole and olanzapine in Huntington's disease.
2002 Mar
Interaction between vanilloid and glutamate receptors in the central modulation of nociception.
2002 Mar 29
Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity.
2002 Sep 15
Adjunctive modafinil in ALS.
2002 Spring
Patents

Sample Use Guides

50 mg twice daily, taken at least 1 hour before or 2 hours after a meal
Route of Administration: Oral
In Vitro Use Guide
In vitro incubation of [14C]riluzole (15 microM) with human hepatic microsomes and NADPH or UDPGA cofactors resulted in formation of N-hydroxyriluzole (K(m) = 30 microM) or an unidentified glucuroconjugate (K(m) = 118 microM). Human microsomal riluzole N-hydroxylation was most strongly inhibited by the CYP1A2 inhibitor alpha-naphthoflavone (IC50 = 0.42 microM). Thus, riluzole is predominantly metabolized by CYP1A2 in human hepatic microsomes to N-hydroxyriluzole.
Name Type Language
RILUZOLE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
RILUZOLE [USP-RS]
Common Name English
RILUZOLE [ORANGE BOOK]
Common Name English
RILUZOLE [INN]
Common Name English
RP 54274
Code English
NSC-753433
Code English
RILUZOLE [EMA EPAR]
Common Name English
EXSERVAN
Brand Name English
RILUZOLE [USP]
Common Name English
2-BENZOTHIAZOLAMINE, 6-(TRIFLUOROMETHOXY)-
Systematic Name English
RP-54274
Code English
TIGLUTIK
Brand Name English
RILUZOLE [USAN]
Common Name English
RILUZOLE [MI]
Common Name English
RILUZOLE [MART.]
Common Name English
NSC-759823
Code English
RILUZOLE [JAN]
Common Name English
2-AMINO-6-(TRIFLUOROMETHOXY)BENZOTHIAZOLE
Systematic Name English
RILUZOLE [USP MONOGRAPH]
Common Name English
RILUZOLE [WHO-DD]
Common Name English
RILUTEK
Brand Name English
BHV-0223
Code English
Classification Tree Code System Code
WHO-ATC N07XX02
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
LIVERTOX 849
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
NDF-RT N0000167094
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
FDA ORPHAN DRUG 509415
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
NDF-RT N0000167094
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
FDA ORPHAN DRUG 510015
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
NDF-RT N0000167094
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
EMA ASSESSMENT REPORTS RILUZOLE ZENTIVA (AUTHORIZED: AMYOTROPHIC LATERAL SCLEROSIS)
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
FDA ORPHAN DRUG 72792
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
NDF-RT N0000167094
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
NDF-RT N0000175740
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
FDA ORPHAN DRUG 508715
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
FDA ORPHAN DRUG 100796
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
WHO-VATC QN07XX02
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
EMA ASSESSMENT REPORTS RILUTEK (AUTHORIZED: AMYOTROPHIC LATERAL SCLEROSIS)
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
EU-Orphan Drug EU/3/14/1401
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
FDA ORPHAN DRUG 563216
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
NCI_THESAURUS C264
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
Code System Code Type Description
IUPHAR
2326
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
MESH
D019782
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
CAS
1744-22-5
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
LACTMED
Riluzole
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
DRUG BANK
DB00740
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
FDA UNII
7LJ087RS6F
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
PUBCHEM
5070
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
RXCUI
35623
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY RxNorm
INN
5912
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
EVMPD
SUB10319MIG
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
WIKIPEDIA
RILUZOLE
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
DRUG CENTRAL
2382
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
EPA CompTox
1744-22-5
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
MERCK INDEX
M9620
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL744
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
NCI_THESAURUS
C47704
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY
USP_CATALOG
1604337
Created by admin on Fri Jun 25 20:36:50 UTC 2021 , Edited by admin on Fri Jun 25 20:36:50 UTC 2021
PRIMARY USP-RS