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Novel nondopaminergic targets for motor features of Parkinson's disease: Review of recent trials

Authors

  • Lorraine V. Kalia MD, PhD,

    1. Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada
    2. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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  • Jonathan M. Brotchie PhD,

    1. Toronto Western Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada
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  • Susan H. Fox MRCP(UK), PhD

    Corresponding author
    1. Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada
    2. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    • Correspondence to: Dr. Susan Fox, Movement Disorders Clinic, Toronto Western Hospital, 399 Bathurst Street, McL 7, Toronto, Ontario, M5T 2S8, Canada; sfox@uhnresearch.ca

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  • Funding agencies: This work was supported by the Krembil Neuroscience Fund (to S.H.F. and J.M.B.). L.V.K. is supported by a Canadian Institutes of Health Research Clinician-Scientist Award.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Neurotransmitters other than dopamine are recognized as having modulatory roles within the basal ganglia and can influence the basal ganglia dopaminergic system to alter activity of the direct and indirect pathways. Many nondopaminergic neurotransmitter systems have been implicated in the mechanisms contributing to the motor features of Parkinson's disease (PD). Thus, it is now well established that neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic, opioidergic, histaminergic, and adenosinergic systems, are affected in the pathogenesis of PD. Nondopaminergic neurotransmitter systems are thus targets for the development of novel therapies for motor symptoms and motor complications in PD. Over the last 5 years, more than 20 randomized, control trials (RCTs) in PD investigating drugs that target several of these nondopaminergic neurotransmitter systems for the treatment of motor features have been completed. There are at least 15 additional RCTs that are ongoing or planned. Here, we review these RCTs to highlight the potential nondopaminergic pharmacological therapies for treatment of motor features of PD. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs will likely yield novel approaches with positive clinical implications. © 2012 Movement Disorder Society

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