Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease

Abstract

Objective:The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).Data Sources:Papers 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 Selection:Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.Results:PD 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.Conclusions:Targeting 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.

Selegiline reduces daytime sleepiness in patients with Parkinson's disease

“…Given the strong impact of EDS, many randomized controlled trials tested different types of possible treatments in these patients: modafinil (Hogl et al., 2002; Ondo et al., 2005; Rodrigues et al., 2016), caffeine (Noyce et al., 2012; Postuma et al., 2012), methylphenidate (Devos et al., 2007), istradefylline (Du & Chen, 2017; Suzuki et al., 2017), and memantine (Ondo et al., 2011), but none of them proved their effectiveness (Seppi et al., 2011; Shen et al., 2018); sodium oxybate showed promising results, but it cannot be considered a first‐choice drug because it is a depressant of the nervous system and respiratory system and has a potential for addiction (Ondo et al., 2008).…”

Study on Effect of Striatal mGluR2/3 in Alleviating Motor Dysfunction in Rat PD Model Treated by Exercise Therapy

“…In recent years, extensive studies have focused on the effect of iGluRs in the occurrence and development of PD and put forward that the excitotoxicity of Glu may be one of the important mechanisms in the occurrence and development of PD (Chotibut et al, 2014). Many studies have indicated that although iGluR antagonist has an anti-PD effect, it is still restricted because the receptor is not specifically distributed in the central nervous system, and nonselective iGluR antagonist may have significant side effects, like cognitive dysfunction and psychotomimetic symptoms, in clinical experiments (Du and Chen, 2017; Masilamoni and Smith, 2018). Therefore, researchers have turned to mGluRs and found that mGluR2/3 may be an important target for the treatment of PD (Chan et al, 2010).…”

Exosomes: Their Role in Pathogenesis, Diagnosis and Treatment of Diseases

“…The α-synuclein protein characterizing PD pathogenesis has been found to be overexpressed, with a recent study reporting that the α-synuclein gene (SNCA) combines its 3′-UTR mRNA with miRNA-7, resulting in the inhibition of transcription and protein expression. In PD, given the decrease in miRNA-7 expression, α-synuclein was found to be toxic to dopamine neurons [ 244 , 245 ]. In addition, the blood plasma of patients is enriched in miRNA-4639-5p as a result of the post-transcriptional downregulation of the DJ-1 gene, given that the decrease in DJ-1 protein levels causes severe oxidative stress and neuron death [ 230 ].…”