Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels.
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 microM). 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 (> or = 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 microM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole.
D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D018482:Muscle, Skeletal / Q000378:metabolism*; D062553:NAV1.4 Voltage-Gated Sodium Channel; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology*; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics; D014162:Transfection
D062553:NAV1.4 Voltage-Gated Sodium Channel; D018696:Neuroprotective Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; C106251:SCN4A protein, human; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019782:Riluzole