Cited by 388Amyotrophic Lateral Sclerosis ResearchNeuroscience and Neuropharmacology ResearchAlzheimer's disease research and treatments

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A Review of the Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating Amyotrophic Lateral Sclerosis: What have we Learned in the Last Decade?: Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating ALS

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Bellingham, Mark C.·2011·CNS Neuroscience & Therapeutics

DOI 10.1111/j.1755-5949.2009.00116.xPMC PMC6493865

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Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure. Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009. A systematic review of this literature found that riluzole had a wide range of effects on factors influencing neural activity in general, and the neuromotor system in particular. These effects occurred over a large dose range (<1 μM to >1 mM). Reported neural effects of riluzole included (in approximate ascending order of dose range): inhibition of persistent Na(+) current = inhibition of repetitive firing < potentiation of calcium-dependent K(+) current < inhibition of neurotransmitter release < inhibition of fast Na(+) current < inhibition of voltage-gated Ca(2+) current = promotion of neuronal survival or growth factors < inhibition of voltage-gated K(+) current = modulation of two-pore K(+) current = modulation of ligand-gated neurotransmitter receptors = potentiation of glutamate transporters. Only the first four of these effects commonly occurred at clinically relevant concentrations of riluzole (plasma levels of 1-2 μM with three- to four-fold higher concentrations in brain tissue). Treatment of human ALS patients or transgenic rodent models of ALS with riluzole most commonly produced a modest but significant extension of lifespan. Riluzole treatment was well tolerated in humans and animals. In animals, despite in vitro evidence that riluzole may inhibit rhythmic motor behaviors, in vivo administration of riluzole produced relatively minor effects on normal respiration parameters, but inhibited hypoxia-induced gasping. This effect may have implications for the management of hypoventilation and sleep-disordered breathing during end-stage ALS in humans.

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“…riluzole has a wide range of neural eﬀects, including inhibition of persistent and fast sodium currents, suppression of neurotransmitter release, diminishment of voltage-gated calcium and potassium currents, and potentiation of calcium-dependent potassium current (Doble, 1996; Bellingham, 2011).”
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See all 388

Authors: Bellingham, M. C.
Affiliations: The University of Queensland (AU)
Corresponding author: Bellingham, Mark C.
ORCID: Bellingham, Mark C.
Venue: CNS Neuroscience & Therapeutics
Publisher: Wiley
Published: 2011-01-17
Volume: 17
Issue: 1
Pages: 4-31
ISSN: 1755-5930 (ISSN-L)
DOI: 10.1111/j.1755-5949.2009.00116.x
PMC: PMC6493865
OpenAlex: W1590729586
Cited by: 388
References: 202
Citations by year: 2026: 16 · 2025: 23 · 2024: 19 · 2023: 23 · 2022: 34 · 2021: 23 · 2020: 31 · 2019: 23 · 2018: 29 · 2017: 34 · 2016: 23 · 2015: 28 · 2014: 22 · 2013: 22 · 2012: 22
FWCI: 2.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1688 d)
Locations: CNS Neuroscience & Therapeutics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: riluzole, amyotrophic lateral sclerosis, mechanism of action, sodium channel inhibition, calcium-activated potassium current, neurotransmitter release, glutamate transporters, neuronal survival, lifespan extension, hypoventilation, sleep-disordered breathing, neuroprotection
MeSH terms: Adult, Aged, Amyotrophic Lateral Sclerosis, Animals, Brain, Dose-Response Relationship, Drug, Humans, Middle Aged, Motor Neurons, Excitatory Amino Acid Antagonists, Neuroprotective Agents, Riluzole

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A Review of the Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating Amyotrophic Lateral Sclerosis: What have we Learned in the Last Decade?: Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating ALS

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