Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function
Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function
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DOI：
10.1038/nm875
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发表时间：
2003-06-01
期刊：
影响因子：
82.9
通讯作者：
Sokoloff, P
中科院分区：
文献类型：
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作者：
Bézard, E;Ferry, S;Sokoloff, P
在用1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱发帕金森病猴模型中，多巴胺D3受体的表达减少。然而，左旋多巴诱导的运动障碍(LID)，类似于帕金森病(PD)患者长期使用左旋多巴后引起的衰弱和耐药的不自主运动，与该受体的过度表达有关。给予D-3受体选择性部分激动剂可显著减轻左旋多巴引起的运动障碍，但不影响左旋多巴的治疗效果。相反，D-3受体拮抗剂对运动障碍的缓解伴随着PD样症状的再现。这些结果表明，D-3受体参与了运动障碍和左旋多巴的治疗作用，部分激动剂可使D-3受体功能正常化，纠正左旋多巴治疗的副作用。
In monkeys rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), expression of the dopamine D 3 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-3 receptor-selective partial agonist strongly attenuated levodopa-induced dyskinesia, but left unaffected the therapeutic effect of levodopa. In contrast, attenuation of dyskinesia by D-3 receptor antagonists was accompanied by the reappearance of PD-like symptoms. These results indicated that the D-3 receptor participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D-3 receptor function and correct side effects of levodopa therapy in patients with PD.