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- Title
Attenuation of levodopa-induced dyskinesia by normalizing dopamine D<sub>3</sub> receptor function.
- Authors
Bezard, Erwan; Ferry, Sandrine; Mach, Ulrich; Stark, Holger; Leriche, Ludovic; Boraud, Thomas; Gross, Christian; Sokoloff, Pierre
- Abstract
In monkeys rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), expression of the dopamine D[SUB3] receptor was decreased. However, levodopa-induced dyskinesia (LID), similar to the debilitating and pharmacoresistant involuntary movements elicited after long-term treatment with levodopa in patients with Parkinson disease (PD), was associated with overexpression of this receptor. Administration of a D[SUB3] receptor-selective partial agonist strongly attenuated levodopa-induced dyskinesia, but left unaffected the therapeutic effect of levodopa. In contrast, attenuation of dyskinesia by D[SUB3] receptor antagonists was accompanied by the reappearance of PD-like symptoms. These results indicated that the D[SUB3] receptor participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D[SUB3] receptor function and correct side effects of levodopa therapy in patients with PD.
- Publication
Nature Medicine, 2003, Vol 9, Issue 6, p762
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm875