OBJECTIVES: There is evidence that an imbalance between glutamatergic and inhibitory neurotransmission may contribute to selective neurodegeneration in amyotrophic lateral sclerosis (ALS). The efficacy of Riluzole in prolonging the survival of patients with ALS has been demonstrated in two large controlled trials. It is believed that Riluzole is a glutamate antagonist, but the exact mode of its action is not known. Data on the effects of Riluzole treatment on excitotoxic amino acid levels in serum are not available. MATERIAL AND METHODS: We prospectively studied 17 patients with ALS (diagnosed according to the El Escorial criteria), who received long-term treatment with Riluzole (100 mg/day). The subjects were evaluated at baseline (before treatment) and after 6, 12 and 18 months on drug. Assessments included the functional status of the patients and serum levels of amino acids. Analysis of the serum amino acids was performed using high performance liquid chromatography techniques at baseline, and after 6, 12 and 18 months of the treatment. RESULTS: At baseline, glutamate, GABA and total amino acid concentration in serum of the ALS patients, mainly in those with severe course of the disease, were increased. During the first 6 months of Riluzole treatment there was a significant decrease of glutamate and total amino acids, afterwards the values returned to the initial high values, or even an 'overshooting' in their levels appeared. We did not observe a similar effect of Riluzole on glutamate and other amino acids in patients with less advanced ALS. CONCLUSIONS: It is suggested that the positive clinical effect of Riluzole in ALS patients may be related, at least partly, to its influence on amino acid metabolism in neural tissues.
OBJECTIVES: There is evidence that an imbalance between glutamatergic and inhibitory neurotransmission may contribute to selective neurodegeneration in amyotrophic lateral sclerosis (ALS). The efficacy of Riluzole in prolonging the survival of patients with ALS has been demonstrated in two large controlled trials. It is believed that Riluzole is a glutamate antagonist, but the exact mode of its action is not known. Data on the effects of Riluzole treatment on excitotoxic amino acid levels in serum are not available. MATERIAL AND METHODS: We prospectively studied 17 patients with ALS (diagnosed according to the El Escorial criteria), who received long-term treatment with Riluzole (100 mg/day). The subjects were evaluated at baseline (before treatment) and after 6, 12 and 18 months on drug. Assessments included the functional status of the patients and serum levels of amino acids. Analysis of the serum amino acids was performed using high performance liquid chromatography techniques at baseline, and after 6, 12 and 18 months of the treatment. RESULTS: At baseline, glutamate, GABA and total amino acid concentration in serum of the ALSpatients, mainly in those with severe course of the disease, were increased. During the first 6 months of Riluzole treatment there was a significant decrease of glutamate and total amino acids, afterwards the values returned to the initial high values, or even an 'overshooting' in their levels appeared. We did not observe a similar effect of Riluzole on glutamate and other amino acids in patients with less advanced ALS. CONCLUSIONS: It is suggested that the positive clinical effect of Riluzole in ALSpatients may be related, at least partly, to its influence on amino acid metabolism in neural tissues.
Authors: Nick S Verber; Stephanie R Shepheard; Matilde Sassani; Harry E McDonough; Sophie A Moore; James J P Alix; Iain D Wilkinson; Tom M Jenkins; Pamela J Shaw Journal: Front Neurol Date: 2019-04-03 Impact factor: 4.003