Levetiracetam improves choreic levodopa-induced dyskinesia in the MPTP-treated macaque

Abstract

L-3,4 dihydroxyphenylalanine (levodopa)-induced dyskinesia in Parkinson's disease patients is characterized by a mixture of chorea and dystonia. Electrophysiological studies suggest that chorea is associated with abnormal synchronization of firing of basal ganglia neurons while dystonia is not. Levetiracetam is a novel anti-epileptic drug known to exhibit unique desynchronizing properties in contrast to other anti-epileptic drugs. We assessed the anti-dyskinetic efficacy of levetiracetam (13, 30 and 60 mg/kg, p.o.) administered in combination with an individually tailored dose of levodopa (Levodopa/carbidopa, 4:1 ratio, 19+/-1.8 mg/kg, p.o.), in six dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaques. Levetiracetam (60 mg/kg) significantly reduced levodopa-induced chorea during the first hour post-treatment but had no effect on dystonia. Levetiracetam, at all doses tested, had no effect on the anti-parkinsonian action of levodopa. These results suggest that levetiracetam may provide a novel therapeutic approach specifically aimed at the choreic form of levodopa-induced dyskinesia.