Riluzole (Rilutek) for ALS
Also known as: Rilutek
The first FDA-approved drug for ALS, riluzole remains part of the standard of care despite modest efficacy.
Mechanism of Action
Riluzole inhibits glutamate release by blocking voltage-gated sodium channels and interfering with intracellular events following receptor binding. It reduces excitotoxic motor neuron death by decreasing presynaptic glutamate release and postsynaptic glutamate receptor activation. The drug also modulates GABA-A receptor function.
General mechanism: Glutamate release inhibitor via sodium channel blockade. Anti-excitotoxic neuroprotection.
Current Evidence
The landmark 1994 trial (Bensimon et al., NEJM) showed a 3-month median survival benefit. Subsequent trials confirmed modest efficacy. Real-world data suggests greater benefit when started early. Riluzole is typically combined with other interventions.
Clinical Status: FDA-approved (1995). Generic available. Standard of care worldwide.
Safety Profile
Generally well-tolerated. Hepatotoxicity requires monitoring (liver function tests). Nausea, fatigue, and dizziness are common side effects.
Key Research Questions
- Does early riluzole initiation significantly improve outcomes vs. delayed start?
- What is the optimal combination of riluzole with emerging therapies like tofersen?
- Can riluzole biomarkers predict individual response?