title: 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.
authors.affiliation: Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Universite Victor Segalen-Bordeaux 2, 146 rue Leo Saignat, BP 28, 33076 Bordeaux Cedex, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hill
authors.forename: Alan R
authors.initials: AR
authors.lastname: Crossman
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Brotchie
authors.forename: Anne
authors.initials: A
authors.lastname: Michel
authors.forename: Renee
authors.initials: R
authors.lastname: Grimée
authors.forename: Henrik
authors.initials: H
authors.lastname: Klitgaard
mesh_terms: D000818:Animals; D002819:Chorea / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D000077287:Levetiracetam; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000503:physiopathology; D008252:Macaca fascicularis; D010889:Piracetam / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D000077287:Levetiracetam; D007980:Levodopa; D010889:Piracetam