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?

Bellingham, Mark C. (2011) 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?. CNS Neuroscience and Therapeutics, 17 1: 4-31.


Author Bellingham, Mark C.
Title 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?
Journal name CNS Neuroscience and Therapeutics  (ERA 2012 Listed)    (ERA 2010 Rank B)   Check publisher's open access policy
Publication date 2011-02
Sub-type Review of research - research literature review (NOT book review
Year available 2010
DOI 10.1111/j.1755-5949.2009.00116.x
Volume number 17
Issue number 1
ISSN 1755-5930
1755-5949
Start page 4
End page 31
Total pages 28
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell
Collection year 2011
Language eng
Subject C1
920111 Nervous System and Disorders
060105 Cell Neurochemistry
Formatted 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 03BCM 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 Ca2+ 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 120132 03BCM 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.
Keyword Hypoxia
Motor neuron disease
Neuronal excitability
Neurotransmitter release
Persistent sodium current
Respiration
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Review of research - research literature review (NOT book review
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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