Definition
A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.
Description
Riluzole is only found in individuals that have used or taken this drug. It is a glutamate antagonist (receptors, glutamate) used as an anticonvulsant (anticonvulsants) and to prolong the survival of patients with amyotrophic lateral sclerosis. [PubChem]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.
Top Gene Interactions
Related Pathways
General Information
- Metabolism: 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.
- Uses/Sources: For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease)
- Health Effects: May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
- Symptoms: Symptoms include such as nausea and fatigue [Wikipedia].
- Treatment: Treatment should be supportive and directed toward alleviating symptoms. Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue. (L1712)
- Route of Exposure: 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
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 85 mg/kg (p.o., mice) (L1859) LD50: 34.5 mg/kg (i.v, mice) (L1859) LD50: 45 mg/kg (p.o., rat) (L1859) LD50: 21 mg/kg (i.v, mice) (L1859)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Sodium channel protein type 2 subunit alpha Dihydrofolate reductase Cystine/glutamate transporter |
10899284 17145705 8813989 12629173 20226190 20059984 |
|
Glutamate receptor ionotropic, NMDA 3A Sodium channel protein type 5 subunit alpha |
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. |
17139284 17016423 |
Riluzole Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Reperfusion Injury | 23.52 |
|
Diabetes Mellitus, Type 2 | 22.7 |
|
Brain Ischemia | 20.4 |
|
Heat Stroke | 18.96 |
|
HIV Wasting Syndrome | 17.86 |
|
Myocardial Reperfusion Injury | 16.64 |
|
Brain Injuries | 15.62 |
|
Stomach Neoplasms | 15.36 |
|
Diabetes Mellitus, Experimental | 15.16 |
|
Status Epilepticus | 14.79 |
|
Mitochondrial Myopathies | 14.77 |
|
Alcoholic liver cirrhosis | 14.58 |
|
Burns | 14.4 |
|
Adenocarcinoma | 13.92 |
|
Polymyositis | 13.69 |
|
Intracerebral hemorrhage | 13.56 |
|
Alzheimer's Disease | 12.13 |
|
Anthracosis | 12.05 |
|
Hemolytic-Uremic Syndrome | 11.85 |
|
Chondrosarcoma, Mesenchymal | 11.71 |
|