Literature DB >> 29672831

Acute Effects of Riluzole and Retigabine on Axonal Excitability in Patients With Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

Maria O Kovalchuk1, Jules A A C Heuberger2, Boudewijn T H M Sleutjes1, Dimitrios Ziagkos2, Leonard H van den Berg1, Toby A Ferguson3, Hessel Franssen1, Geert Jan Groeneveld2.   

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.

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Year:  2018        PMID: 29672831     DOI: 10.1002/cpt.1096

Source DB:  PubMed          Journal:  Clin Pharmacol Ther        ISSN: 0009-9236            Impact factor:   6.875


  14 in total

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Journal:  RSC Med Chem       Date:  2021-01-14

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Journal:  Brain Commun       Date:  2020-02-20

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8.  Human amyotrophic lateral sclerosis excitability phenotype screen: Target discovery and validation.

Authors:  Xuan Huang; Kasper C D Roet; Liying Zhang; Amy Brault; Allison P Berg; Anne B Jefferson; Jackie Klug-McLeod; Karen L Leach; Fabien Vincent; Hongying Yang; Anthony J Coyle; Lyn H Jones; Devlin Frost; Ole Wiskow; Kuchuan Chen; Rie Maeda; Alyssa Grantham; Mary K Dornon; Joseph R Klim; Marco T Siekmann; Dongyi Zhao; Seungkyu Lee; Kevin Eggan; Clifford J Woolf
Journal:  Cell Rep       Date:  2021-06-08       Impact factor: 9.423

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Authors:  Namita A Goyal; James D Berry; Anthony Windebank; Nathan P Staff; Nicholas J Maragakis; Leonard H van den Berg; Angela Genge; Robert Miller; Robert H Baloh; Ralph Kern; Yael Gothelf; Chaim Lebovits; Merit Cudkowicz
Journal:  Muscle Nerve       Date:  2020-01-22       Impact factor: 3.217

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