Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function.
Nat Med. 2003-05-12; 9(6): 762-767
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1. Nat Med. 2003 Jun;9(6):762-7. Epub 2003 May 12.
Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor
Bézard E(1), Ferry S, Mach U, Stark H, Leriche L, Boraud T, Gross C, Sokoloff P.
(1)Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor
Segalen, 33076 Bordeaux, France.
In monkeys rendered parkinsonian with
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), expression of the dopamine
D3 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 D3
receptor-selective partial agonist strongly attenuated levodopa-induced
dyskinesia, but left unaffected the therapeutic effect of levodopa. In contrast,
attenuation of dyskinesia by D3 receptor antagonists was accompanied by the
reappearance of PD-like symptoms. These results indicated that the D3 receptor
participated in both dyskinesia and the therapeutic action of levodopa, and that
partial agonists may normalize D3 receptor function and correct side effects of
levodopa therapy in patients with PD.
PMID: 12740572 [Indexed for MEDLINE]