Abstract
Increased excitability of motor neurons in patients with amyotrophic lateral sclerosis (ALS) may be a relevant factor leading to motor neuron damage. This randomized, double-blind, three-way crossover, placebo-controlled study evaluated peripheral motor nerve excitability testing as a biomarker of hyperexcitability and assessed the effects of riluzole and retigabine in 18 patients with ALS. We performed excitability testing at baseline, and twice after participants had received a single dose of either 100 mg riluzole, 300 mg retigabine, or placebo. Between- and within-day repeatability was at least acceptable for 14 out of 18 recorded excitability variables. No effects of riluzole on excitability testing were observed, but retigabine significantly decreased strength-duration time-constant (9.2%) and refractoriness at 2 ms (10.2) compared to placebo. Excitability testing was shown to be a reliable biomarker in patients with ALS, and the acute reversal of previously abnormal variables by retigabine justifies long-term studies evaluating the impact on disease progression and survival.
© 2018 American Society for Clinical Pharmacology and Therapeutics.
Publication types
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Amyotrophic Lateral Sclerosis / drug therapy*
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Amyotrophic Lateral Sclerosis / pathology
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Amyotrophic Lateral Sclerosis / physiopathology
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Axons / drug effects*
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Axons / pathology
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Carbamates / administration & dosage*
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Carbamates / adverse effects
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Carbamates / pharmacokinetics
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Cross-Over Studies
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Double-Blind Method
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Electromyography
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Evoked Potentials, Motor / drug effects*
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Excitatory Amino Acid Antagonists / administration & dosage*
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Excitatory Amino Acid Antagonists / adverse effects
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Excitatory Amino Acid Antagonists / pharmacokinetics
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Female
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Humans
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Male
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Middle Aged
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Motor Neurons / drug effects*
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Motor Neurons / pathology
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Netherlands
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Neuroprotective Agents / administration & dosage*
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Neuroprotective Agents / adverse effects
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Neuroprotective Agents / pharmacokinetics
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Phenylenediamines / administration & dosage*
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Phenylenediamines / adverse effects
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Phenylenediamines / pharmacokinetics
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Refractory Period, Electrophysiological / drug effects
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Riluzole / administration & dosage*
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Riluzole / adverse effects
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Riluzole / pharmacokinetics
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Time Factors
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Treatment Outcome
Substances
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Carbamates
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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Phenylenediamines
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ezogabine
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Riluzole