The latest pharmacological strategies for the management of levodopa-induced dyskinesias
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摘要: 左旋多巴诱导的异动症(levodopa-induced dyskinesia,LID)是帕金森病多巴胺治疗的常见副作用,严重影响患者的生活质量。其发生机制尚不清楚,但是帕金森病异动症动物模型提供了关于左旋多巴诱导的异动症机制的重要知识。目前除了调整治疗方案之外只有少数几种能减轻LID症状的药物,并且这些药物不能延缓病程,所以现在急需研究新的药物来干预其进展。本综述从机体多巴胺能、谷氨酸能、5-羟色胺能、阿片、GABA能、腺苷、肾上腺神经递质等系统出发,阐述致病机理的同时综述相关的最新治疗药物,其中还包括一些尚未进入临床、只进行了动物试验的药物。除了治疗异动症的经典药物金刚烷胺、吗啡之外,本综述还加入了马福利特、咖啡因等新近正在研究的药物,在常用剂型之外还加入了新的剂型,以快速缓解症状或减轻多巴胺的波动性刺激。本综述旨在为异动症的治疗提供更多的备选方案以期早日达到控制疾病进展的目的。Abstract: Levodopa-induced dyskinesias (LID) is the most common side effect in Parkinson's disease (PD) treatment with dopaminergic and it seriously affect the patients' living quality. The underlying mechanism and pathological substrate of LID are not fully understood but animal models of parkinsonism with LID have provided important knowledge about the mechanisms underlying LID. Now in addition to adjust the treatment plan there is only a few drugs can relieve symptoms of LID and these drugs can not delay the course of the disease. So there is an urgent need for research on new drugs to make an intervention on its progress. Here we review the most relevant advances in relation to the dopaminergic system, the glutamatergic system, the serotonergic system, the opioid system, the GABAergic system, the adenosine system, the adrenergic neurotransmission and the related newly studied medicines to treat LID. Some of these drugs are not used clinically and only studied on animal models. Except for the classic medicines for LID treatment amantadine and morphine, there are also newly studied medicines such as mavoglurant and caffeine. For the classic druges there are newly studied dosage form for the sake of control the LID symptom rapidly or remission the pulsatile stimulation of DA receptors. The ultimate aim of this review is provide more choices for LID treatment and control the process of LID as soon as possible.
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Key words:
- Parkinson's disease /
- Dopamine /
- Levodopa-induced dyskinesias /
- Treatment Pharmacology
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