Article

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

Hannover Medical School, Hanover, Lower Saxony, Germany
Muscle & Nerve (Impact Factor: 2.28). 10/2002; 26(4):539-45. DOI: 10.1002/mus.10230
Source: PubMed

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.

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    • "It was demonstrated to reduce glutamate excitotoxicity by inhibiting glutamate release and/or modifying the postsynaptic glutamate receptor cascade (Martin et al., 1993; Mantz et al., 1994; Rothstein and Kuncl, 1995; De Sarro et al., 2000). In addition, emerging evidence has unraveled that riluzole can inhibit voltage-gated Na + channels (Hebert et al., 1994; Siniscalchi et al., 1997; Song et al., 1997; Yokoo et al., 1998; Zona et al., 1998; Mohammadi et al., 2002). This effect has been proposed to be mainly responsible for the prevention of epilepsy and cellular death caused by this drug (Hebert et al., 1994). "
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