BLOCKADE OF GLUTAMATERGIC TRANSMISSION AS TREATMENT FOR DYSKINESIAS AND MOTOR FLUCTUATIONS IN PARKINSONS-DISEASE

In animal models of Parkinson's disease (PD), glutamate antagonists di minish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extend ed to the human disease, by evaluating the effects of three non-compet itive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four sepa rate trials, adjuvant therapy with these drugs reduced LD-induced dysk inesias and motor fluctuations. These findings support the view that d rugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.