Therapies for dopaminergic-induced dyskinesias in parkinson disease

Existing and emerging strategies for managing L‐dopa–induced dyskinesias (LIDs) in patients with Parkinson disease have involved either delaying the introduction of L‐dopa therapy, treatment with an antidyskinetic agent, using a therapy or delivery system that can provide continuous dopaminergic sti...

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Bibliographic Details
Published in:Annals of neurology 2011-06, Vol.69 (6), p.919-927
Main Authors: Gottwald, Mildred D., Aminoff, Michael J.
Format: Article
Language:English
Subjects:
Animals
Antiparkinson Agents - adverse effects
Biological and medical sciences
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dopamine - metabolism
Dopamine Agents - therapeutic use
Drug Delivery Systems
Dyskinesia, Drug-Induced - etiology
Dyskinesia, Drug-Induced - therapy
Humans
Medical sciences
Neurology
Parkinson Disease - drug therapy
Parkinson's disease
Transcranial Magnetic Stimulation
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Summary:Existing and emerging strategies for managing L‐dopa–induced dyskinesias (LIDs) in patients with Parkinson disease have involved either delaying the introduction of L‐dopa therapy, treatment with an antidyskinetic agent, using a therapy or delivery system that can provide continuous dopaminergic stimulation, or using novel agents that target receptors implicated in the mechanisms underlying LIDs. Treatment with dopamine agonists such as pramipexole or ropinirole allows levodopa to be delayed, but once levodopa is added to the drug regimen the usual course of onset of dyskinesias is observed. Amantadine, an N‐methyl‐D‐aspartate antagonist, is so far the only approved compound with evidence of providing a sustained antidyskinetic benefit in the absence of unacceptable side effects. These findings support the hypothesis of glutamate overactivity in the development of dyskinesias. More continuous delivery of dopaminergic medication, such as through intraintestinal or subcutaneous routes, is promising but invasive and associated with injection site reactions. As a result of molecular research and elucidation of the role of a variety of neurotransmitters in the mechanism of LIDs, new compounds have been identified, including those that modulate the direct and indirect striatal output pathways; some of these new agents are in the early stages of development or undergoing proof‐of‐concept evaluation as antidyskinetic agents. Ann Neurol 2011;69:919–927
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.22423