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Non-Dopaminergic Treatments for Motor Control in Parkinson’s Disease: An Update

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Abstract

Glutamatergic, noradrenergic, serotonergic, and cholinergic systems play a critical role in the basal ganglia circuitry. Targeting these non-dopaminergic receptors remains a focus of ongoing research to improve Parkinson’s disease (PD) motor symptoms, without the potential side effects of dopamine replacement therapy. This review updates advancements in non-dopaminergic treatments for motor control in PD since 2013. To date, no non-dopaminergic selective drug has shown significant long-term efficacy as monotherapy in PD. The largest area of development in non-dopaminergic targets has been for motor complications of dopamine replacement therapy (motor fluctuations and dyskinesia). For treatment of motor fluctuations, safinamide, zonisamide, and istradefylline are currently approved, and novel glutamatergic and serotonergic drugs are in development. Long-acting formulations of amantadine are approved for treating dyskinesia. Several non-dopaminergic drugs have failed to show anti-dyskinetic efficacy, while some are still in development. Non-dopaminergic targets are also being pursued to treat specific motor symptoms of PD. For example, CX-8998 (a calcium channel modulator) is being evaluated for PD tremor and rivastigmine may improve gait dysfunction in PD. Drug repurposing continues to be a key strategy for non-dopaminergic targets in PD, but the field needs to increase discovery and availability of such drugs.

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Author notes

  1. Susan H. Fox

    Present address: Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Division of Neurology, Department of Medicine, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada

  2. Paulina Gonzalez-Latapi, Suvorit Subhas Bhowmick and Gerard Saranza contributed equally to this work.

Authors and Affiliations

  1. Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Division of Neurology, Department of Medicine, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada

    Paulina Gonzalez-Latapi, Suvorit Subhas Bhowmick & Gerard Saranza

  2. Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada

    Susan H. Fox

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  1. Paulina Gonzalez-Latapi
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  2. Suvorit Subhas Bhowmick
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  3. Gerard Saranza
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Correspondence to Susan H. Fox.

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This study was supported in part by the Edmond J. Safra Philanthropic Foundation, Vadodara Institute of Neurological Sciences, and the Parkinson’s Foundation through their support of the fellowship training of PG-L., SB and GS, respectively.

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The authors declare no conflict of interest.

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SSB, PG-L, and GS performed the detailed review of the literature and undertook the writing of the manuscript. SF provided critical comments, recommendations, and editorial contributions.

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Gonzalez-Latapi, P., Bhowmick, S.S., Saranza, G. et al. Non-Dopaminergic Treatments for Motor Control in Parkinson’s Disease: An Update. CNS Drugs 34, 1025–1044 (2020). https://doi.org/10.1007/s40263-020-00754-0

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