Levodopa-induced dyskinesias in Parkinson's disease: emerging treatments.
Levodopa-induced dyskinesias in Parkinson's disease: emerging treatments.
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DOI：
10.2147/ndt.s36693
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发表时间：
2013
影响因子：
3.2
通讯作者：
Konitsiotis S
中科院分区：
文献类型：
--
作者：
Bargiotas P;Konitsiotis S
帕金森病治疗仍然集中在使用L-3，4-二羟基苯丙氨酸（左旋多巴或L-dopa）来对症治疗该疾病的主要临床特征，尽管在过去几十年中进行了深入的药理学研究。然而，无论其有效性如何，长期使用左旋多巴导致与疾病进展相结合的运动并发症的发展，称为左旋多巴诱导的运动障碍（LID）。LID是基底神经节回路功能组织发生深刻变化的结果，可能与左旋多巴对纹状体多巴胺能受体的慢性和脉动刺激有关。因此，几十年来，针对LID的潜在有效药物的关键特征是其确保大脑中更连续的多巴胺能刺激的能力。关于LIDS的病理生理学的知识不断增加，越来越多的证据表明参与非多巴胺能系统提出了未来更有前途的治疗方法的可能性。在目前的审查中，我们专注于新的治疗LIDS在帕金森氏病，主要是基于代理人干扰多巴胺能，多巴胺能，腺苷，肾上腺素能和胆碱能神经传递，目前正在测试或临床开发。
Parkinson’s disease therapy is still focused on the use of L-3,4-dihydroxyphenylalanine (levodopa or L-dopa) for the symptomatic treatment of the main clinical features of the disease, despite intensive pharmacological research in the last few decades. However, regardless of its effectiveness, the long-term use of levodopa causes, in combination with disease progression, the development of motor complications termed levodopa-induced dyskinesias (LIDs). LIDs are the result of profound modifications in the functional organization of the basal ganglia circuitry, possibly related to the chronic and pulsatile stimulation of striatal dopaminergic receptors by levodopa. Hence, for decades the key feature of a potentially effective agent against LIDs has been its ability to ensure more continuous dopaminergic stimulation in the brain. The growing knowledge regarding the pathophysiology of LIDs and the increasing evidence on involvement of nondopaminergic systems raises the possibility of more promising therapeutic approaches in the future. In the current review, we focus on novel therapies for LIDs in Parkinson’s disease, based mainly on agents that interfere with glutamatergic, serotonergic, adenosine, adrenergic, and cholinergic neurotransmission that are currently in testing or clinical development.