Get access

The α2 adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates

Authors

  • Tom H. Johnston PhD,

    1. Division of Brain, Imaging, and Behaviour – Systems Neuroscience, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Canada
    Search for more papers by this author
  • Susan H. Fox MRCP, PhD,

    1. Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, Canada
    Search for more papers by this author
  • Matthew J. Piggott PhD,

    1. School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, Western Australia, Australia
    Search for more papers by this author
  • Juha-Matti Savola MD, PhD,

    1. Santhera Pharmaceuticals (Switzerland) Ltd, Liestal, Switzerland
    Search for more papers by this author
  • Jonathan M. Brotchie PhD

    Corresponding author
    1. Division of Brain, Imaging, and Behaviour – Systems Neuroscience, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Canada
    • Toronto Western Research Institute, 399 Bathurst Street, Mc-11-419, Toronto M5T2S7, Ontario, Canada
    Search for more papers by this author

  • Potential conflict of Interest: Nothing to report.

Abstract

Reduction in the antiparkinsonian benefit of levodopa is a major complication of long-term levodopa treatment in advanced Parkinson's disease (PD). Such loss of benefit arises because of reduced duration of action and appearance of disabling dyskinesia. We assess the potential of the α2 adrenergic antagonist fipamezole to reduce motor complications in parkinsonian macaques. MPTP-lesioned macaques were treated acutely with fipamezole (10 mg/kg) alone and in combination with two doses of levodopa. Fipamezole extended both duration and quality of antiparkinsonian action of levodopa. Duration of antiparkinsonian action, on time, was increased by up to 75% while “good-quality” on time, i.e., that not associated with disabling dyskinesia, was increased by up to 98%. Combination of fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at least equivalent to that provided by the higher dose levodopa alone. However, with the combination, antiparkinsonian benefit was of much better quality. The proportion of on time without disabling dyskinesia (79%) was significantly greater than that with high dose levodopa alone (45%). Increased duration and quality of levodopa action may represent therapeutically valuable actions of α2 adrenergic antagonists. © 2010 Movement Disorder Society

Get access to the full text of this article

Ancillary