Perspective

Royal College of Surgeons in Ireland, School of Medicine, Dublin, Ireland

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Christine Sun

Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), Montreal, QC, H3A 2B4, Canada

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Philippe Huot

*Author for correspondence: Tel.: +1 514 934 8026;

E-mail Address: philippe.huot@mcgill.ca

https://orcid.org/0000-0002-5464-8334

Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), Montreal, QC, H3A 2B4, Canada

Movement Disorder Clinic, Division of Neurology, Department of Neurosciences, McGill University Health Centre, Montreal, QC, H3A 2B4, Canada

Department of Neurology & Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada

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Published Online:4 May 2023https://doi.org/10.2217/nmt-2022-0039

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Abstract

Levodopa is the most effective agent for treating the symptoms of Parkinson's disease (PD). However, levodopa-induced dyskinesia remains a significant complication that manifests after few years of treatment, for which therapeutic options remain limited. Several agonists of the serotonin type 1A (5-HT_1A) receptor with varying levels of efficacy and interaction at other sites, have been tested in the clinic. Clinical trials testing 5-HT_1A agonists have yielded inconsistent results in alleviating dyskinesia, especially that the antidyskinetic benefit observed was often accompanied by an adverse effect on motor function. In this article, we summarize and analyze the various clinical trials performed with 5-HT_1A agonists in PD patients with dyskinesia and offer perspectives on the future of this class of agents in PD.

Plain language summary

After prolonged treatment with levodopa, patients with Parkinson's disease might start to experience abnormal involuntary movements, called ‘dyskinesias’. These abnormal movements may be difficult to cope with since they can occur for several hours during the day and can hamper the quality of life. A potential approach to reduce the severity of dyskinesia, which has been the focus of extensive research, consists of stimulating a target inside the brain called the 5-HT_1A receptor. Several drugs harbouring this mechanism of action have been tested in clinical studies. Here, we provide an overview of these clinical studies and discuss their results.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 13, No. 2

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Received 21 November 2022

Accepted 23 March 2023

Published online 4 May 2023

Published in print April 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nmt-2022-0039

Author contributions

J Al-Kassmy and C Sun wrote the first draft of the manuscript and conducted literature review. P Huot reviewed and critiqued the manuscript.

Financial & competing interests disclosure

P Huot has had research support from Parkinson Canada, Parkinson Québec, Fonds de Recherche Québec – Santé, the Weston Brain Institute, the Michael J Fox Foundation for Parkinson's Research, the Natural Sciences and Engineering Research Council of Canada and Healthy Brains for Healthy Lives. P Huot has received payments from Abbvie, adMare BioInnovations, ConSynance Therapeutics, Neurodiem, Sanford Burnham Prebys, Sunovion and Througline Strategy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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5-HT1A agonists for levodopa-induced dyskinesia in Parkinson's disease

Abstract

Plain language summary

References

5-HT_1A agonists for levodopa-induced dyskinesia in Parkinson's disease