Columbia University Medical Center, 110 W 168th Street, New York, NY 10032, USA.
Expert Rev Neurother. 2013 Jun;13(6):719-29. doi: 10.1586/ern.13.47.
Motor fluctuations and dyskinesias are common sequelae of Parkinson's disease (PD) that may limit function and quality of life. With disease progression, striatal dopamine concentration becomes closely linked to plasma levodopa levels, which vary considerably with standard oral regimens. Exposure of striatal dopamine receptors to wildly fluctuating transmitter levels is thought to contribute to the development of dyskinesias and motor fluctuations. Continuous dopaminergic delivery has been shown to reduce motor complications in advanced PD patients, and has been hypothesized to prevent their incidence when given as early therapy in mild PD. In this article, the authors outline the rationale for continuous dopaminergic delivery and review clinical strategies implementing the concept, including transdermal rotigotine, subcutaneous apomorphine infusion, intraduodenal infusion of levodopa gel and the investigational oral levodopa formulation IPX066.
运动波动和运动障碍是帕金森病(PD)的常见后遗症,可能会限制其功能和生活质量。随着疾病的进展,纹状体多巴胺浓度与血浆左旋多巴水平密切相关,而标准口服方案会导致左旋多巴水平发生较大变化。纹状体多巴胺受体暴露于剧烈波动的递质水平被认为是导致运动障碍和运动波动的原因之一。持续多巴胺能传递已被证明可减少晚期 PD 患者的运动并发症,并假设在轻度 PD 中早期给予治疗时可预防其发生。本文作者概述了持续多巴胺能传递的基本原理,并回顾了实施该概念的临床策略,包括经皮罗替戈汀贴剂、皮下注射阿扑吗啡、左旋多巴凝胶经十二指肠内输注和研究性口服左旋多巴制剂 IPX066。