The role of glutamatergic transmission in the pathogenesis of levodopa-induced dyskinesias. Potential therapeutic approaches.

Dyskinesias are the most frequent adverse effect of chronic levodopa therapy in patients with Parkinson's disease (PD). Current pharmacological treatment for this problem is unsatisfactory. Recently, there is evidence for the role of glutamate in the basal ganglia neuronal circuitry in the generation of dyskinesias. If indeed glutamatergic overactivity beyond the dopaminergic synapses plays a role in the pathogenesis of these involuntary movements, there is hope that its suppression may be beneficial without causing loss of levodopa efficacy and parkinsonian deterioration. Indeed, NMDA receptor antagonists such as amantadine and dextrometorphan can reduce such dyskinesias. We tested the efficacy of riluzole, an inhibitor of glutamatergic transmission in the inhibition of levodopa-induced dyskinesias.