Effects of Mexiletine and Lacosamide on Nerve Excitability in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
07
03
2022
accepted:
12
06
2022
pubmed:
29
6
2022
medline:
25
10
2022
entrez:
28
6
2022
Statut:
ppublish
Résumé
Selective voltage-gated sodium channel blockers are of growing interest as treatment for pain. For drug development of such compounds, it would be critical to have a biomarker that can be used for proof-of-mechanism. We aimed to evaluate whether drug-induced changes in sodium conductance can be detected in the peripheral nerve excitability profile in 18 healthy subjects. In a randomized, double-blind, 3-way crossover study, effects of single oral doses of 333 mg mexiletine and 300 mg lacosamide were compared with placebo. On each study visit, motor and sensory nerve excitability measurements of the median nerve were performed (predose; and 3 and 6 hours postdose) using Qtrac. Treatment effects were calculated using an analysis of covariance (ANCOVA) with baseline as covariate. Mexiletine and lacosamide had significant effects on multiple motor and sensory nerve excitability variables. Depolarizing threshold electrotonus (TEd
Identifiants
pubmed: 35762293
doi: 10.1002/cpt.2694
pmc: PMC9795956
doi:
Substances chimiques
Lacosamide
563KS2PQY5
Mexiletine
1U511HHV4Z
Voltage-Gated Sodium Channel Blockers
0
Sodium
9NEZ333N27
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1008-1019Informations de copyright
© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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