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Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult‐type nicotinic receptor channels
Author(s) -
Mohammadi Bahram,
Lang Nicolas,
Dengler Reinhard,
Bufler Johannes
Publication year - 2002
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.10230
Subject(s) - sodium channel , riluzole , nicotinic agonist , skeletal muscle , chemistry , recombinant dna , endocrinology , medicine , pharmacology , receptor , sodium , biochemistry , glutamate receptor , gene , organic chemistry
Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage‐gated neuronal sodium channels at very low concentrations (about 0.1 μM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch‐clamp technique, we applied riluzole on recombinant voltage‐gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage‐gated skeletal muscle sodium channels, shifting the midpoint of the steady‐state inactivation curve to more negative potentials, but only in comparatively high concentrations (≥ 0.1 mM). At these concentrations, riluzole also caused an open‐channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage‐gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 μM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 539–545, 2002