Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels

Muscle Nerve. 2002 Oct;26(4):539-45. doi: 10.1002/mus.10230.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Humans
  • Ion Channel Gating / drug effects
  • Membrane Potentials / drug effects
  • Muscle, Skeletal / metabolism*
  • NAV1.4 Voltage-Gated Sodium Channel
  • Neuroprotective Agents / pharmacology*
  • Nicotinic Antagonists / pharmacology
  • Patch-Clamp Techniques
  • Receptors, Nicotinic / drug effects*
  • Recombinant Proteins / metabolism
  • Riluzole / pharmacology*
  • Sodium Channel Agonists
  • Sodium Channel Blockers*
  • Sodium Channels / genetics
  • Transfection

Substances

  • NAV1.4 Voltage-Gated Sodium Channel
  • Neuroprotective Agents
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Recombinant Proteins
  • SCN4A protein, human
  • Sodium Channel Agonists
  • Sodium Channel Blockers
  • Sodium Channels
  • Riluzole