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首页> 外文期刊>CNS & Neurological Disorders - Drug Targets >D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinson's Disease
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D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinson's Disease

机译：D1和功能选择性多巴胺激动剂作为帕金森氏病的神经保护剂

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摘要

Parkinson's disease (PD) is a progressive neurodegenerative disorder that results in major motor disturbances due primarily to loss of midbrain dopamine neurons. The mainstream treatment has been dopaminergic replacement therapy aimed at symptomatic relief, with the gold standard drug being the dopamine precursor levodopa. The general dogma has been that levodopa works primarily by indirectly activating the D2 family of dopamine receptors. Recently, a number of direct dopamine agonists that target the D2 and D3 dopamine receptors have been used as dopaminergic replacement strategies. Although these direct D2 and D3 drugs cause only modest improvement in motor function compared to levodopa, they can delay the initiation of levodopa and can act synergistically with levodopa. In addition, they can delay the onset of levodopa-related motor complications. Recent imaging data also suggest that they may have neuroprotective effects. Whereas D2/D3 agonists have received much attention as several drugs are available for clinical trials and usage, there has been a large body of data showing that the D1 receptor actually may play a larger role in restoration of normal motor function. This review examines the current use of dopamine D2/D3 agonists in treatment of PD and their potential for providing neuroprotection. Furthermore, we also examine the potential that D1 agonists might have in neuroprotective actions in the disease progression.
机译：帕金森氏病（PD）是一种进行性神经退行性疾病，主要由于中脑多巴胺神经元的丧失而导致严重的运动障碍。主流治疗方法是针对症状缓解的多巴胺能替代疗法，其中金标准药物为多巴胺前体左旋多巴。普遍的教条是左旋多巴主要通过间接激活多巴胺受体D2家族起作用。近来，许多靶向D2和D3多巴胺受体的直接多巴胺激动剂已被用作多巴胺能替代策略。尽管与左旋多巴相比，这些直接的D2和D3药物仅引起运动功能的适度改善，但它们可以延迟左旋多巴的启动并可以与左旋多巴协同作用。此外，它们可以延迟左旋多巴相关运动并发症的发作。最近的成像数据还表明它们可能具有神经保护作用。 D2 / D3激动剂已受到广泛关注，因为有几种药物可用于临床试验和使用，但大量数据表明D1受体实际上可能在恢复正常运动功能中起更大作用。这篇综述检查了多巴胺D2 / D3激动剂在PD治疗中的当前用途及其提供神经保护作用的潜力。此外，我们还检查了D1激动剂在疾病进展中可能在神经保护作用中具有的潜力。

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