Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
Ann Neurol. 2011 Jun;69(6):919-27. doi: 10.1002/ana.22423.
Existing and emerging strategies for managing L-dopa-induced dyskinesias (LIDs) in patients with Parkinson disease have involved either delaying the introduction of L-dopa therapy, treatment with an antidyskinetic agent, using a therapy or delivery system that can provide continuous dopaminergic stimulation, or using novel agents that target receptors implicated in the mechanisms underlying LIDs. Treatment with dopamine agonists such as pramipexole or ropinirole allows levodopa to be delayed, but once levodopa is added to the drug regimen the usual course of onset of dyskinesias is observed. Amantadine, an N-methyl-D-aspartate antagonist, is so far the only approved compound with evidence of providing a sustained antidyskinetic benefit in the absence of unacceptable side effects. These findings support the hypothesis of glutamate overactivity in the development of dyskinesias. More continuous delivery of dopaminergic medication, such as through intraintestinal or subcutaneous routes, is promising but invasive and associated with injection site reactions. As a result of molecular research and elucidation of the role of a variety of neurotransmitters in the mechanism of LIDs, new compounds have been identified, including those that modulate the direct and indirect striatal output pathways; some of these new agents are in the early stages of development or undergoing proof-of-concept evaluation as antidyskinetic agents.
现有的和新兴的策略来管理左旋多巴诱导的运动障碍（LIDs）在帕金森病患者中，要么延迟左旋多巴治疗的引入，要么用抗运动障碍药物治疗，要么使用一种能提供持续多巴胺刺激的治疗或给药系统，要么使用针对LIDs 发病机制中涉及的受体的新型药物。用多巴胺激动剂，如普拉克索或罗匹尼罗治疗可以延迟左旋多巴的使用，但一旦左旋多巴加入药物治疗方案，通常会观察到运动障碍的发生。金刚烷胺，一种 N-甲基-D-天冬氨酸拮抗剂，是迄今为止唯一一种有证据表明在没有不可接受的副作用的情况下提供持续抗运动障碍益处的批准药物。这些发现支持谷氨酸过度活动在运动障碍发展中的假说。更持续地输送多巴胺药物，如通过肠内或皮下途径，是有前途的，但具有侵入性，并且与注射部位反应有关。由于分子研究和阐明各种神经递质在 LIDs 机制中的作用，已经确定了新的化合物，包括那些调节直接和间接纹状体输出途径的化合物；其中一些新的药物正处于早期开发阶段，或正在进行作为抗运动障碍药物的概念验证评估。
