Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naïve primates

Authors

  • Lance A. Smith PhD,

    1. Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom
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  • Michael J. Jackson BSc,

    1. Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom
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  • Ghassan Al-Barghouthy MSc,

    1. Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom
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  • Sarah Rose PhD,

    1. Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom
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  • Mikko Kuoppamaki MD,

    1. Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom
    2. Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA
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  • Warren Olanow MD,

    1. Satakunta Central Hospital and Satakunnan Neurologipalvelu Oy, Pori, Finland
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  • Peter Jenner PhD

    Corresponding author
    1. Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom
    • Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, United Kingdom
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Abstract

Long-acting dopamine agonist drugs induce a lower incidence of dyskinesia in MPTP-treated primates and patients with Parkinson's disease compared to pulsatile treatment with levodopa, supporting the concept of continuous dopaminergic stimulation as a means of dyskinesia avoidance. We examined the effects of L-dopa administered with or without the COMT inhibitor entacapone on dyskinesia induction in previously untreated MPTP-treated common marmosets. Administration of L-dopa (12.5 mg/kg p.o.) plus carbidopa twice daily produced fluctuating improvement in motor behavior coupled with dyskinesia. Coadministration with entacapone produced similar patterns of motor improvement and dyskinesia that were not different from that produced by L-dopa alone. Treatment with L-dopa (6.25 mg/kg p.o.) plus carbidopa four times daily reversed motor disability and induced dyskinesia in a manner that was not different from the twice-daily treatment regimens. However, coadministration with entacapone produced more continuous improvement in locomotor activity with less dyskinesia than animals treated with L-dopa four times daily alone. These data support the notion that pulsatile stimulation contributes to the development of dyskinesia and suggests that more frequent dosing of L-dopa plus entacapone may be a useful treatment strategy for patients in the early stages of Parkinson's disease. © 2004 Movement Disorder Society

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