Effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on striatal neurochemical markers in the rat, with special reference to the dopamine, choline, GABA and glutamate synaptosomal high affinity uptake systems.
Riluzole, a new compound with anticonvulsant properties, was found to induce a dose-dependent decrease in the uptake of 3H-dopamine, 3H-GABA and 3H-glutamate into striatal synaptosomes when added to the incubation medium or after in vivo administration, whereas an inhibition of 3H-choline uptake was detected only in the in vitro experiments. Interestingly, riluzole affected 3H-dopamine and 3H-glutamate uptake differentially since 3H-dopamine uptake was found to be more sensitive to the compound. Moreover, riluzole inhibited 3H-dopamine uptake competitively and 3H-glutamate uptake non-competitively, which further suggests that the action of the compound is selective. After in vivo injection, riluzole did not affect the striatal dopamine, DOPAC, serotonin, 5HIAA, glutamate, aspartate or GABA contents. Since this compound was previously reported to induce a decrease in the spontaneous release of glutamate, serotonin, dopamine and possibly acetylcholine, the hypothesis is put forward that riluzole may, at least at high concentrations, have general effects on the striatal nerve terminals affecting both the uptake and release processes. This action may be correlated with the recently identified blocking properties of the compound on the sodium channels, as previously shown for local anaesthetics.
Samuel
D
D
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle du CNRS, Marseille, France.
Blin
O
O
Dusticier
N
N
Nieoullon
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D015415:Biomarkers; D002794:Choline / Q000378:metabolism / Q000493:pharmacokinetics*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003470:Culture Media; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005971:Glutamates / Q000378:metabolism / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000493:pharmacokinetics*
D015415:Biomarkers; D003470:Culture Media; D005971:Glutamates; D014179:Neurotransmitter Uptake Inhibitors; D013844:Thiazoles; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; D001224:Aspartic Acid; D012701:Serotonin; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D019782:Riluzole; D002794:Choline; D004298:Dopamine