Effect of Riluzole on serum amino acids in patients with amyotrophic lateral sclerosis.
OBJECTIVE
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.


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.
Niebroj-Dobosz
I
I
Department of Neurology, Medical University of Warsaw, Poland. hubert@amwaw.edu.pl
Janik
P
P
Kwieciński
H
H
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood*; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy; D001224:Aspartic Acid / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000097:blood; D005998:Glycine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood; D012016:Reference Values; D019782:Riluzole / Q000627:therapeutic use*; D013995:Time; D005680:gamma-Aminobutyric Acid / Q000097:blood
D000596:Amino Acids; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D019782:Riluzole; D005998:Glycine