Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden.
Curr Opin Pharmacol. 2018 Feb;38:81-89. doi: 10.1016/j.coph.2018.03.003. Epub 2018 Apr 3.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by typical motor features that result from dopamine (DA) depletion in the striatum. DA replacement therapy with L-DOPA is the most efficacious symptomatic treatment, but causes complications that limit its utility, in particular, L-DOPA-induced dyskinesia (LID). LID is primarily caused by pre-synaptic and post-synaptic changes in DA neurotransmission, although it also depends on altered glutamatergic transmission at several nodes of the cortico-basal ganglia-thalamocortical network. The important functional interplay between dopaminergic and glutamatergic systems has stimulated an interest in metabotropic glutamate receptors (mGluRs) as potential therapeutic targets in PD and LID. We here review the antiparkinsonian and antidyskinetic potential of modulating group I, II, and III mGluRs in several preclinical models of PD. We also provide an update on clinical trials evaluating mGluR5 or mGluR4 ligands in PD.
帕金森病（PD）是一种神经退行性疾病，其特征是典型的运动特征，这些特征是由于纹状体中多巴胺（DA）耗竭引起的。用左旋多巴进行 DA 替代疗法是最有效的对症治疗方法，但会引起并发症，限制了其应用，特别是左旋多巴诱导的运动障碍（LID）。LID 主要是由 DA 神经传递的突触前和突触后变化引起的，尽管它也取决于皮质基底神经节 - 丘脑皮质网络的几个节点处谷氨酸能传递的改变。多巴胺能和谷氨酸能系统之间的重要功能相互作用激发了人们对代谢型谷氨酸受体（mGluRs）作为 PD 和 LID 潜在治疗靶点的兴趣。我们在这里回顾了在几种 PD 临床前模型中调节 I 组、II 组和 III 组 mGluRs 的抗帕金森病和抗运动障碍潜力。我们还提供了关于评估 mGluR5 或 mGluR4 配体在 PD 中的临床试验的最新信息。
