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AMYOTROPHIC lateral sclerosis (ALS) is a neurological disorder neuropathologically characterized by a progressive degeneration of upper and lower motoneurones. The origin of the neuronal death is presently unknown but recent findings suggest that neurodegeneration could be related to an excitotoxic disorder. We have recently shown that the cerebrospinal fluid (CSF) of ALS patients contains for neurones in cultures cytotoxic factors whose toxic properties are mediated by AMPA/kainate receptors, a subgroup of glutamate post-synaptic receptors. This study reports that riluzole partially prevents in vitro the neuronal degeneration produced by ALS CSF (neuronal survival 60.6 ± 13.1%). Riluzole (5 X 10−7 M) which reduces excitatory amino acid release, could represent a new pharmacological agent susceptible to be proposed to patients affected by this dramatic neurological disease.