Objective: To reappraise the role of the µ opioid receptor as a therapeutic target for L-DOPA-induced dyskinesia.

Background: Parkinson’s disease (PD) is commonly treated with the dopamine precursor L-DOPA, but its prolonged use causes abnormal involuntary movements, or L-DOPA-induced dyskinesia (LID). Studies in animal models of PD have indicated that LID is associated with increased synthesis of certain opioid co-transmitters in the basal ganglia, suggesting hyperactive opioid transmission. Attempts have, therefore, been made to alleviate LID using opioid receptor antagonists. Reports that both antagonists and agonists of the µ opioid receptor may alleviate LID in primate models and also the failure of non-specific antagonists in pilot clinical trials raises concerns about the functional significance of the available data on the opioid system in PD and LID.

Method: After in vitro characterization of the brain regional functional activity of the µ opioid receptor in the MPTP-lesioned primate model of LID, we tested prototypical µ opioid receptor agonists, antagonists and partial agonists for efficacy.

Results: We demonstrated that both oral and discrete intracerebral administration of a µ receptor agonist, but not of an antagonist, ameliorated LID.

Conclusion: Our results call for a re-appraisal of the functional significance of endogenous basal ganglia opioids  in PD and LID and for the exploration of µ opioid agonists as a potential treatment for LID.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mu-opioid-receptor-agonism-not-antagonism-for-the-treatment-of-l-dopa-induced-dyskinesia-in-parkinsons-disease/