Drug/Small Molecule:

riluzole

Overview

Generic Names:	riluzole
IUPAC Name:	6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
Trade Names:	Rilutek; Riluzole HCl
PharmGKB Accession Id:	PA451251

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)

ATC Therapeutic Category

• N07XX:Other nervous system drugs

Pharmacology and Interactions

Mechanism Of Action

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.

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.

Food Interactions

Take on an empty stomach 1 hour before or 2 hours after meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

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.

Protein Binding

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

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.

Chemical Properties

Chemical Formula:

C₈H₅F₃N₂OS

SMILES Code:

c1cc2c(cc1OC(F)(F)F)sc(n2)N

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

234.198 / 234.0075

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	CYP1A2	PK	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP1A2

Drug Targets

• GRIN3A
• SCN5A

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.