Motor fluctuations represent a therapeutic challenge in the management of Parkinson's disease. They occur as a consequence of a combination of factors, including chronic pulsatile oral levodopa treatment, progressive loss of nigrostriatal nerve terminals, and reduced endogenous dopamine storage and release capacity. As mobility becomes progressively dependent on peripheral levodopa bioavailability, physicians need to adjust medications to preserve functionality and independence. However, fluctuations are common and can manifest with both motor and non-motor symptoms, such as depression, anxiety, or pain, making their identification in clinical practice complex. Moreover, attempts to extend the effect of levodopa are limited by delayed or erratic gastric emptying, or hampered by poor tolerability. So far, extended-release levodopa formulations have failed to provide a stable levodopa concentration and a reduced pulsatile stimulation of dopamine receptors. Therefore, research has moved to identify different routes of delivering levodopa and other dopaminergic agents.

中文翻译：

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帕金森氏病患者多巴胺能药物输送的新途径。

运动波动代表了帕金森氏病治疗中的治疗挑战。它们的发生是多种因素共同作用的结果，包括慢性搏动性口服左旋多巴治疗，黑质纹状体神经末梢的逐渐丧失以及内源性多巴胺的储存和释放能力降低。随着活动性逐渐取决于周围左旋多巴的生物利用度，医生需要调整药物以保持功能性和独立性。然而，波动是常见的，并且可以表现为运动和非运动症状，例如抑郁，焦虑或疼痛，这使得它们在临床实践中的识别变得复杂。而且，扩大左旋多巴作用的尝试受到胃排空延迟或不规律的限制，或者由于耐受性差而受到阻碍。迄今为止，左旋多巴的缓释制剂未能提供稳定的左旋多巴浓度和减少的多巴胺受体的搏动刺激。因此，研究已经转移到确定递送左旋多巴和其他多巴胺能药物的不同途径。