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

Summary— Riluzole, a new compound with anticonvulsant properties, was found to induce a dose‐dependent decrease in the uptake of 3 H‐dopamine, 3 H‐GABA and 3 H‐glutamate into striatal synaptosmes when added to the incubation medium or after in vivo administration, whereas an inlubition of 3 H‐choline uptake was detected only in the in vitro experiments. Interestingly, riluzole affected 3 H‐dopamine and 3 H‐glutamate uptake differentially since 3 H‐dopamine uptake was found to be more sensitive to the compound. Moreover, riluzole inhibited 3 H‐dopamine uptake competitively and 3 H‐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.