Objective: To investigate the mechanism(s) of action of xenon inhalation for the treatment of L-DOPA-induced dyskinesia.

Background: L-dopa-induced dyskinesia (LID) is one of the most common and frequently dose-limiting complications of pharmacologic therapy for Parkinson disease (PD). These typically choreiform movements, usually occurring at the time of peak levodopa effect, occur in 40% to 50% of patients after 5 years of therapy but have a reported incidence as high as 94% in a carefully conducted prospective study of patients under treatment for 15 years. Among the cellular alterations underlying LID, impairment of cortico-striatal synaptic plasticity is the main electrophysiological signature associated with the appearance of abnormal involuntary movements (AIMs).

Methods: The rationale for testing Xenon in LID was based upon its NMDA receptor antagonistic properties an action similar to amantadine, the only one agent to date to effectively reduce LID. Here, we show that xenon (xenon-O2 50%/50%) reduces L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-OHDA-lesioned rat and the MPTP monkey models of Parkinson’s disease, with comparable efficacy than amantadine.

Results: We here show that xenon gas exposition reverses maladaptive corticostriatal plasticity associated with levodopa-induced-dyskinesia and that xenon inhalation ameliorates disabling dyskinesias in the rat and non-human primate gold-standard experimental models of PD and dyskinesia.

Conclusions: Our data pave the way for clinical testing of this safe unconventional approach to control the severity of LID in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/inhaling-xenon-ameliorates-l-dopa-induced-dyskinesia-in-parkinson-disease-through-normalizing-maladaptive-corticostriatal-plasticity/