Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset

Michael P. Hill, Erwan Bezard, Steven G. McGuire, Alan R. Crossman, Jonathan M. Brotchie, Ann Michel, Renee Grimée, Henrik Klitgaard

    Research output: Contribution to journalArticlepeer-review

    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. © 2003 Movement Disorder Society.
    Original languageEnglish
    Pages (from-to)1301-1305
    Number of pages4
    JournalMovement Disorders
    Volume18
    Issue number11
    DOIs
    Publication statusPublished - Nov 2003

    Keywords

    • Dyskinesia
    • L-dopa
    • Neuronal firing patterns
    • Ropinirole
    • Synchronization

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