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Article . 2015
License: CC BY NC SA
Data sources: CONICET Digital
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Movement Disorders
Article . 2015 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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New treatments for levodopa‐induced motor complications

Authors: Rascol, Olivier; Pérez Lloret, Santiago; Ferreira, Joaquim;

New treatments for levodopa‐induced motor complications

Abstract

AbstractLevodopa (l‐dopa)‐induced motor complications, including motor fluctuations and dyskinesia, affect almost all patients with Parkinson's disease (PD) at some point during the disease course, with relevant implications in global health status. Various dopaminergic and nondopaminergic pharmacological approaches as well as more invasive strategies including devices and functional surgery are available to manage such complications. In spite of undisputable improvements during the last decades, many patients remain significantly disabled, and a fully satisfying management of l‐dopa–induced motor complications is still an important unmet need of PD therapy. This article reviews the recent trial results published from 2013 to April 2015 about pharmacological and nonpharmacological interventions to treat motor complications. Randomized controlled trials conducted in patients suffering from already established complications showed that new levodopa (l‐dopa) formulations such as intrajejunal l‐dopa–carbidopa infusion and bilayered extended‐release l‐dopa–carbidopa (IPX066) can improve motor fluctuations. Positive results were also obtained with a new monoamine oxidase B (MAO‐B) inhibitor (safinamide) and a catechol‐O‐methyltransferase COMT inhibitor (opicapone). Pilot data suggest that new formulations of dopamine agonists (inhaled apomorphine) are also of potential interest. The development of novel nondopaminergic adenosine A2A antagonists (istradefylline, preladenant, and tozadenant) to treat motor fluctuations showed conflicting results in phase 2 and phase 3 trials. For dyskinesia, trials with new amantadine extended‐release formulations confirmed the interest of the glutamatergic N‐methyl‐d‐aspartate (NMDA) antagonist approach. Positive pilot antidyskinetic effects were also recently reported using serotonin agents such as eltoprazine and glutamate mGluR5 modulators such as mavoglurant. However, the translation to clinical practice of such innovative concepts remains challenging, because subsequent phase 2 trials conducted to confirm the antidyskynetic effects of mavoglurant failed, leading to the interruption of the development of this compound for this indication. © 2015 International Parkinson and Movement Disorder Society

Country
Argentina
Keywords

Dyskinesia, Drug-Induced, Complicaciones Motoras, Parkinson Disease, Antiparkinson Agents, Levodopa, Enfermeda de Parkinson, https://purl.org/becyt/ford/3.2, Tratamiento, Animals, Humans, https://purl.org/becyt/ford/3

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    popularity
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    influence
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
107
Top 10%
Top 10%
Top 1%
Green