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

Stem definition	Drug id	CAS RN
	2382	1744-22-5

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
0.10	g	O

ADMET properties:

Property	Value	Reference
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:

Date	Agency	Company	Orphan
Dec. 12, 1995	FDA	COVIS PHARMA SARL

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (acidic/basic)
pKa1	3.47	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Sodium channel protein type 5 subunit alpha	Ion channel	Q14524	SCN5A_HUMAN	BLOCKER			WOMBAT-PK	CHEMBL
Small conductance calcium-activated potassium channel protein 3	Ion channel	Q9UGI6	KCNN3_HUMAN	ACTIVATOR	EC50	4.90	IUPHAR
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN		Ki	5.76	DRUG MATRIX
Glutamate receptor ionotropic, NMDA 3A	Ion channel	Q8TCU5	NMD3A_HUMAN				WOMBAT-PK
Intermediate conductance calcium-activated potassium channel protein 4	Ion channel	O15554	KCNN4_HUMAN	ACTIVATOR	IC50	5.70	IUPHAR
Small conductance calcium-activated potassium channel protein 1	Ion channel	Q92952	KCNN1_HUMAN	ACTIVATOR	EC50	4.68	IUPHAR
Pteridine reductase 1	Enzyme		PTR1_LEIMA		Ki	5.40	CHEMBL
Small conductance calcium-activated potassium channel protein 2	Unclassified		KCNN2_RAT	ACTIVATOR	EC50	4.89	IUPHAR

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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