Department of Neurology, IRCCS San Raffaele Pisana, Rome, Italy.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S68-71. doi: 10.1016/S1353-8020(09)70784-9.
Continuous dopaminergic stimulation is a therapeutic concept for the management of Parkinson's disease (PD) that proposes that continuous, as opposed to discontinuous or pulsatile, stimulation of striatal dopamine receptors will delay or prevent the onset of levodopa-related motor complications. This hypothesis has arisen from studies of the normal basal ganglia demonstrating that nigral dopaminergic neurons normally fire continuously and striatal dopamine levels are relatively constant. In MPTP monkeys, pulsatile stimulation of striatal dopamine receptors with short-acting agents is associated with the induction of molecular and physiologic changes in basal ganglia neurons and the development of motor complications. These are avoided when dopaminergic therapies are delivered in a more continuous manner. Studies in animal models support this hypothesis, demonstrating that long-acting dopamine agonists are associated with a decreased risk of motor complications in comparison to short-acting formulations of levodopa. Similarly, continuous infusion of dopamine agonists ropinirole and rodigotine reduces dyskinesia associated with intermittent doses of oral formulations of the same drug. The current challenge is to develop a long-acting formulation of levodopa that simulates the pharmacokinetic pattern seen with infusions of levodopa in attempt to provide comparable benefits with an oral levodopa treatment strategy.
持续多巴胺能刺激是一种治疗帕金森病 (PD) 的概念，它提出持续刺激而非间断或脉冲刺激纹状体多巴胺受体将延迟或预防与左旋多巴相关的运动并发症的发生。这一假设源于对正常基底神经节的研究，表明黑质多巴胺能神经元通常连续放电，纹状体多巴胺水平相对稳定。在 MPTP 猴中，用短效药物脉冲刺激纹状体多巴胺受体与基底神经节神经元的分子和生理变化的诱导以及运动并发症的发展有关。当多巴胺能治疗以更连续的方式提供时，这些并发症可以避免。动物模型研究支持这一假设，表明长效多巴胺激动剂与运动并发症的风险降低相关，而与左旋多巴的短效制剂相比。同样，长效多巴胺激动剂罗匹尼罗和罗替高汀的持续输注减少了与相同药物口服制剂间歇性剂量相关的运动障碍。目前的挑战是开发一种长效左旋多巴制剂，模拟与左旋多巴输注相关的药代动力学模式，试图通过口服左旋多巴治疗策略提供类似的益处。
