Pharmaceuticals -> Nervous system -> Other nervous system drugs
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals
LogP2.3
Solubility · 2 items
3.95e-02 g/L
22.1 [ug/mL] (The mean of the results at pH 7.4)
Human Drugs · 5 items
Breast Feeding; Lactation; Excitatory Amino Acid Antagonists; Neuroprotective Agents
FDA approved drugs -> Active ingredient
EMA approved medicines: Human medicine
EMA approved medicines: Human medicine
FDA approved drugs -> Active ingredient
Melting Point119 °C
Physical DescriptionSolid
Physicochemical properties
Melting point
116 · 116-118°C
Boiling point
296.3 · 296.3±50.0 °C(Predicted)
Density
Safety & regulation
GHS classification
GHS Classification · 4 items
Danger
H301 (91.9%): Toxic if swallowed [Danger Acute toxicity, oral]
P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 74 reports by companies from 6 notifications to the ECHA C&L Inventory.
Hazard information
Hazard Classes and CategoriesAcute Tox. 3 (91.9%)
Toxicology
TreatmentTreatment should be supportive and directed toward alleviating symptoms. Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue. (L1712)
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
Hepatotoxicity · 1 item
Serum aminotransferase elevations occur in approximately up to 12% of patients on long term riluzole therapy, but elevations above 3 times the upper limit of normal (ULN) occur in less than 3% of patients. These elevations are usually mild-to-moderate in severity and are rarely associated with symptoms. Most elevations resolve spontaneously, but persistent or marked elevations require drug discontinuation or dose modification. Routine monitoring of serum aminotransferase levels is recommended for the first 6 months of therapy. Clinically apparent liver injury due to riluzole is rare, but several cases have been reported, arising after 1 to 12 months of therapy and characterized by a hepatocellular or mixed pattern of serum enzyme elevations. Immunoallergic and autoimmune features were uncommon. Most cases were mild to moderate in severity and recovery was rapid upon drug discontinuation, but evidently fatal cases have been reported to the sponsor.
Exposure Routes
Chemistry & industry
Pharmacology
ATC Code · 3 items
N07XX02
N - Nervous system
QN - Nervous system
Protein Binding96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range.
Pharmacodynamics · 1 item
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 <i>in vivo</i> 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.
Mechanism of Action · 1 item
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 (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.
Biological Half-LifeThe mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.
Metabolism/Metabolites · 3 items
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.
Riluzole has known human metabolites that include 5-hydroxy-riluzole, 4-hydroxy-riluzole, N-Hydroxyriluzole, and 7-hydroxy-riluzole.
6.1 A · 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials
Hazard Classifications
2 Oral · Acute Tox. 2 Oral
Toxicity
50 in · LD50 in mice (mg/kg): 46 i.p.; 67 orally (Mizoule)
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%.
Toxicity Summary · 1 item
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 (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.
Signs and SymptomsSymptoms include such as nausea and fatigue [Wikipedia].
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury · 6 items
Drug Induced Liver Injury Rank (DILIrank 2.0)
Riluzole
vMost-DILI-concern
8
Warnings & precautions
DOI:10.1016/j.drudis.2016.02.015
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
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.
Half Life: The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.
FDA Pharmacological Classification · 6 items
7LJ087RS6F
RILUZOLE
Established Pharmacologic Class [EPC] - Benzothiazole
Chemical Structure [CS] - Benzothiazoles
Riluzole is a Benzothiazole.
RILUZOLE
MeSH Pharmacological Classification · 3 items
Drugs used to prevent SEIZURES or reduce their severity.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Absorption, Distribution and ExcretionRiluzole 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%.
Cellular LocationsMembrane
Uses & manufacturing
Uses · 2 items
Use (kg; approx.) in Germany (2009): >100
For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease)
Applications · 6 items
DescriptionRiluzole belongs to the derivative of benzothiazole with neuroprotective, potential anti-depressant and anxiolytic activities, which is used in the treatment of a certain type of nerve disease called amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). It is effective to delay the onset of ventilator-dependence or tracheostomy in selected patients, slow down the deterioration of this disease and probably prolong survival by approximately two to three months. Besides, studies have proved that riluzole has anti-depressant activity for refractory depression and serves as an anxiolytic in the treatment of obsessive-compulsive disorder and generalized anxiety disorder. However, riluzole does not cure the ALS and reverse nerve damage or muscle weakness. It is believed to function as an inhibitor of a natural substance called glutamate. It helps protect the nerves in the brain and spinal cord from too much of glutamate which may contribute to the nerve damage. Riluzole is available in both tablet and liquid form. The liquid formulation may be more suitable for patients with swallowing difficulties.
DescriptionRilutek was launched in Germany, the UK and US (orphan drug status) for treatment of amyotrophic lateral sclerosis (ALS) and is the first drug approved for this indication. A one step synthesis from 4-(trifluoromethoxy)aniline provides a supply of the compound. The source of its neuroprotective and anticonvulsant activity is not clearly understood. It antagonizes excitatory amino acids and blocks presynaptic release of glutamate, is an antagonist of NMDA-induced acetylcholine release and inhibited glutamate and quisqualate induced increases in cGMP but does not bind to NMDA or Kainic receptors. Rilutek has no affinity for glutamate, GABAbenzodiazepine, glycine and adenosine receptors. It easily crosses the blood brain barrier and depresses glutamatergic neurotransmission, stabilizes voltagedependent Na channels in their inactive form and activates G-protein dependent processes.
UsesA neuroprotective agent. Modulates glutamatergic transmission. A glutamate release inhibitor. An anticonvulsant.
