• Juan-Juan Du and Sheng-Di Chen.
• Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
• Chin. Med. J. 2017 Aug 5; 130 (15): 1856-1866.

ObjectiveThe aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).Data SourcesPapers in English published in PubMed, Cochrane, and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the ongoing clinical trials in the website of clinicaltrials.gov.Study SelectionArticles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.ResultsPD is conventionally treated with dopamine replacement strategies, which are effective in the early stages of PD. Long-term use of levodopa could result in motor complications. Recent studies revealed that nondopaminergic systems such as adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator pathways could include potential therapeutic targets for motor symptoms, including motor fluctuations, levodopa-induced dyskinesia, and gait disorders. Some nondopaminergic drugs, such as istradefylline and amantadine, are currently used clinically, while most such drugs are in preclinical testing stages. Transitioning of these agents into clinically beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite positive findings at the preclinical level.ConclusionsTargeting nondopaminergic transmission could improve some motor symptoms in PD, especially the discomfort of dyskinesia. Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa, further investigation is required to ensure their success.

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