Movement Disorders Program, Cleveland Clinic Florida, Weston, FL 33331, USA.
Cleve Clin J Med. 2012 Jul;79 Suppl 2:S8-13. doi: 10.3949/ccjm.79.s2a.02.
There are two major causes of disability in patients with Parkinson disease: motor fluctuations that occur when a dose of levodopa becomes ineffective, leading to a "wearing off," and hyperkinetic movements (dyskinesias) caused by excessive levels of dopamine. The utility of continuous levodopa treatment is therefore limited by motor complications. Pharmacologic options to treat wearing off include adding (or increasing the dosage of) levodopa, adding (or increasing the dosage of) a dopamine agonist, or adjunctive treatment with a monoamine oxidase inhibitor or catechol-O-methyltransferase inhibitor. Dyskinesias will respond to a reduction in levodopa dosage at the expense of worsening parkinsonism and an increase in the number of "off" episodes. Continuous dopamine stimulation may overcome the pulsatile stimulation of postsynaptic dopamine receptors produced by standard oral formulations of levodopa that lead to motor complications.
左旋多巴剂量失效时出现的运动波动(“开-关”现象),以及多巴胺水平过高引起的不自主运动(运动障碍)。因此,持续左旋多巴治疗的效果受到运动并发症的限制。治疗“开-关”现象的药物选择包括添加(或增加剂量)左旋多巴、添加(或增加剂量)多巴胺激动剂,或联合使用单胺氧化酶抑制剂或儿茶酚-O-甲基转移酶抑制剂。减少左旋多巴剂量可改善运动障碍,但会使帕金森病恶化,“关”期次数增加。持续多巴胺刺激可以克服由标准口服左旋多巴制剂引起的突触后多巴胺受体的脉冲式刺激,从而避免运动并发症。