http://nro.sagepub.com/content/19/2/137.abstract?etoc
Abstract
Amyotrophic lateral sclerosis (Lou
Gehrig’s disease) is a devastating neurodegenerative disorder for which
the only licensed
treatment is riluzole. Although riluzole clinical
efficacy is rather limited, its use has important implications for
identifying
those parameters that might improve its clinical
benefits (dose, timing, disease stage) and for its off-label
administration
in other neurodegenerative diseases, such as spinal
cord injury. Studies of riluzole also have an intrinsically heuristic
value to unveil mechanisms regulating the
excitability of brain and spinal neurons because this drug is a
pharmacological
tool to probe the function of certain ion channels,
or to study neurotransmitter release processes, and intracellular
neuroprotective
pathways. The present review focuses on how
riluzole acts on brain and spinal neurons within motor networks, what
mechanisms
can be deduced from its effects, and what
conditions may favor its use to contrast neurodegeneration or to
ameliorate late
symptoms like spasticity. Taking as an example the
experimental neurodegeneration caused by overactivation of glutamatergic
synapses (excitotoxicity), it seems likely that
protection of motor networks by riluzole involves selected
administration
timing and dosing to target processes for releasing
glutamate from very active synapses or for dampening repetitive firing
by hyperfunctional motor cells.
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