Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study

Experimental evidence suggests that glutamatergic receptor blockade may improve the motor response complications associated with long-term levodopa treatment in Parkinson's disease (PD) patients. Our objective was to evaluate the acute effect of amantadine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on levodopa-induced dyskinesias, and to gain further insights into the antidyskinetic mechanism of this drug. Nine PD patients with motor fluctuations and severely disabling peak of dose dyskinesias received their first morning levodopa dose, followed by a 2-hour intravenous amantadine (200 mg) or placebo infusion, on two different days. Parkinsonian symptoms and dyskinesias were assessed every 15 minutes during the infusion and for 3 hours thereafter, while patients were taking their usual oral antiparkinsonian therapy, by means of Unified Parkinson's Disease Rating Scale (UPDRS, motor examination), tapping test, and a modified Abnormal Involuntary Movement Scale (AIMS). Intravenous amantadine acutely improved levodopa-induced dyskinesias by 50%without any loss of the anti-parkinsonian benefit from levodopa. This study confirms the antidyskinetic effect of amantadine and strengthens the rationale for using antiglutamatergic drugs in the treatment of parkinsonian motor fluctuations.