title: Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.
abstract: Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.
authors.affiliation: Motac Neuroscience Ltd, Manchester, United Kingdom.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hill
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: Steven G
authors.initials: SG
authors.lastname: McGuire
authors.forename: Alan R
authors.initials: AR
authors.lastname: Crossman
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Brotchie
authors.forename: Ann
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: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000009:adverse effects*; D002144:Callithrix; D015259:Dopamine Agents / Q000009:adverse effects* / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007211:Indoles / Q000009:adverse effects*; D000077287:Levetiracetam; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007211:Indoles; C046649:ropinirole; D000077287:Levetiracetam; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010889:Piracetam