CAS 1744-22-5|riluzole|6-(trifluoromethoxy)-1,3-benzothiazol-2-amine|Rilutek|Riluzole HCl|riluzole|Riluzole|PK-26124|Rilutek|RP-54274|Riluzole(Rilutek)|2-Amino-6-trifluoro-methoxybenzothiazole|6-(Tr...

General Information

Structure

Molecular Formula

C₈H₅F₃N₂OS

Molecular Mass

234.1983096

Exact Mass

234.00746845

Charge

InChI

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)

InChIKey

FTALBRSUTCGOEG-UHFFFAOYSA-N

Canonic Smiles

Nc1nc2c(s1)cc(cc2)OC(F)(F)F

Isomeric Smiles

s1c2c(nc1N)ccc(OC(F)(F)F)c2

Calculated Properties

JChem

Acid pKa

16.440592

H Acceptors

H Donor

LogD (pH = 5.5)

3.353241

LogD (pH = 7.4)

3.3992848

Log P

3.3999074

Molar Refractivity

44.3727

Polarizability

18.69663

Polar Surface Area

48.14

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

2.83

LOG S

-3.77

Solubility (Water)

3.95e-02 g/l

Data Source

Names and Identifiers

IUPAC Traditional name

riluzole 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

IUPAC name

6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

Brand Name

RilutekRiluzole HCl

Synonyms

riluzoleRiluzolePK-26124RilutekRP-54274Riluzole(Rilutek)2-Amino-6-trifluoro-methoxybenzothiazole6-(Trifluoromethoxy)-1,3-benzothiazol-2-amine2-Amino-6-(trifluoromethoxy)-1,3-benzothiazole 97%6-(trifluoromethoxy)benzo[d]thiazol-2-amineRiluzole2-Amino-6-(trifluoromethoxy)benzothiazole6-(Trifluoromethoxy)-2-aminobenzothiazole6-(Trifluoromethoxy)-2-benzothiazolamine2-Amino-6-(trifluoromethoxy)benzothiazole6-Trifluoromethoxy-benzothiazol-2-ylamine6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

Names and Identifiers

Registration numbers

CAS Number

1744-22-5

PubChem SID

4650809424278006160964083

PubChem CID

5070

MDL Number

MFCD00210213

Registration numbers

Properties

Pharmacology Properties

Gene Information

rat ... Scnn1g(24768)

Mechanism of Action

High-voltage calcium channel blockade

Glutamate transporter activation

N-methyl-D-aspartate (NMDA)/glutamate receptor antagonism

Sodium channel blockade

Properties

Related Proteins

No Data Available

Click here to submit data

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00740

Drug Groups

approved; investigational

Description

A glutamate antagonist (receptors, glutamate) used as an anticonvulsant (anticonvulsants) and to prolong the survival of patients with amyotrophic lateral sclerosis. [PubChem]

Indication

For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease)

Pharmacology

Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. 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.

Affected Organisms

Humans and other mammals

Biotransformation

Riluzole is extensively metabolized to six major and a number of minor metabolites, which have not all been identified to date. Metabolism is mostly hepatic, consisting of cytochrome P450–dependent hydroxylation and glucuronidation. CYP1A2 is the primary isozyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to contribute significantly to riluzole metabolism in humans.

Absorption

Riluzole is well-absorbed (approximately 90%), with average absolute oral bioavailability of about 60% (CV=30%). A high fat meal decreases absorption, reducing AUC by about 20% and peak blood levels by about 45%.

Half Life

The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.

Protein Binding

96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range.

References

• 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]

• 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]

• 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]

• 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]

• Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. [Pubmed]

• 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. Epub 2008 Apr 26. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1614

Research Area: Neurological Disease
Biological Activity:
Riluzole(Rilutek) is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase the survival approximately 3–5 months. [1] Its pharmacological activities in motor neurons include the following: 1) an inhibitory effect on glutamate release 2) inactivation of voltage-dependent sodium channels 3) interference with intracellular events that follow transmitter binding at excitatory amino acid receptors. In animal models, this agent has been shown to exhibit myorelaxant and sedative activities, apparently due to the blockade of glutamatergic neurotransmission. [1]

MP Biomedicals

02193713

A glutamate release inhibitor which also blocks voltage-dependent Na⁺ channels and inhibits GABA uptake.

Sigma Aldrich

R3772

Biochem/physiol Actions
Glutamate release inhibitor

R116

Biochem/physiol Actions
Glutamate release inhibitor; anticonvulsant

TRC

R510000

A neuroprotective agent. Modulates glutamatergic transmission. A glutamate release inhibitor. An anticonvulsant.

Molecule Details

References

PubChem Literature

From Data Sources

• Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. Pubmed

• http://en.wikipedia.org/wiki/Riluzole

• Mantz, et al., Eur. J. Pharmacol. , 257 : R7, (1994).

• Mizoule, J., et al.: Neuropharmacology, 24, 767 (1985)

• Wahl, F., et al.: Eur. J. Pharmacol., 230, 209 (1993) Bensimon, G., et al.: N. Engl. J. Med., 330, 585 (1994)

• Eur. Pat., 1982, Pharmindustrie, 50 551; CA, 97, 44352, (pharmacol)

• Rowland, L.P., N. Engl. J. Med., 1994, 330, 636

• Yagupol'skii, L.M. et al., Zh. Obshch. Khim., 1963, 33, 2301, (synth)

• Mizoule, J. et al., Neuropharmacology, 1985, 24, 767, (pharmacol)

• Mantz, J., CNS Drug Rev., 1996, 2, 40, (rev)

• Bensimon, G. et al., N. Engl. J. Med., 1994, 330, 585, (clin trial)

• Tsai, C. et al., Neurol. Neurobiol., 1987, 24, 79, (pharmacol)

• Mantz, J. et al., Eur. J. Pharmacol., 1994, 257, R7, (pharmacol)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

IUPAC Traditional name

riluzole 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

IUPAC name

6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

Brand Name

RilutekRiluzole HCl

Synonyms

Registration numbers

CAS Number

1744-22-5

PubChem SID

4650809424278006160964083

PubChem CID

5070

MDL Number

MFCD00210213

Molecule Details

DrugBank

DB00740

Drug Groups

approved; investigational

Description

A glutamate antagonist (receptors, glutamate) used as an anticonvulsant (anticonvulsants) and to prolong the survival of patients with amyotrophic lateral sclerosis. [PubChem]

Indication

For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease)

Pharmacology

Affected Organisms

Humans and other mammals

Biotransformation

Absorption

Half Life

The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.

Protein Binding

96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range.

References

• Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1614

MP Biomedicals

02193713

A glutamate release inhibitor which also blocks voltage-dependent Na⁺ channels and inhibits GABA uptake.

Sigma Aldrich

R3772

Biochem/physiol Actions
Glutamate release inhibitor

R116

Biochem/physiol Actions
Glutamate release inhibitor; anticonvulsant

TRC

R510000

A neuroprotective agent. Modulates glutamatergic transmission. A glutamate release inhibitor. An anticonvulsant.

References

PubChem Literature

From Data Sources

• Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. Pubmed

• http://en.wikipedia.org/wiki/Riluzole

• Mantz, et al., Eur. J. Pharmacol. , 257 : R7, (1994).

• Mizoule, J., et al.: Neuropharmacology, 24, 767 (1985)

• Wahl, F., et al.: Eur. J. Pharmacol., 230, 209 (1993) Bensimon, G., et al.: N. Engl. J. Med., 330, 585 (1994)

• Eur. Pat., 1982, Pharmindustrie, 50 551; CA, 97, 44352, (pharmacol)

• Rowland, L.P., N. Engl. J. Med., 1994, 330, 636

• Yagupol'skii, L.M. et al., Zh. Obshch. Khim., 1963, 33, 2301, (synth)

• Mizoule, J. et al., Neuropharmacology, 1985, 24, 767, (pharmacol)

• Mantz, J., CNS Drug Rev., 1996, 2, 40, (rev)

• Bensimon, G. et al., N. Engl. J. Med., 1994, 330, 585, (clin trial)

• Tsai, C. et al., Neurol. Neurobiol., 1987, 24, 79, (pharmacol)

• Mantz, J. et al., Eur. J. Pharmacol., 1994, 257, R7, (pharmacol)

Bioactivity

PubChem BioAssay

Properties

Pharmacology Properties

Gene Information

rat ... Scnn1g(24768)

Mechanism of Action

High-voltage calcium channel blockade

Glutamate transporter activation

N-methyl-D-aspartate (NMDA)/glutamate receptor antagonism

Sodium channel blockade

Molecule

ID:620