Department for Parkinson's Disease, IRCCS San Camillo and University of Padova, Venice, Italy.
J Neurol. 2010 Nov;257(Suppl 2):S305-8. doi: 10.1007/s00415-010-5714-1.
Motor fluctuations and dyskinesias occur in the majority of patients with Parkinson's disease (PD) and are likely to result from changes in dopamine production, storage and release, occurring as consequences of the nigrostriatal degenerative process. All studies comparing levodopa versus dopamine agonist early therapy indicate that initiation with agonists is associated with a reduced risk of motor complications -in particular, dyskinesias- possibly because agonists' longer half-lives provide continuous dopaminergic delivery. In advanced PD patients, switching from a pulsatile to continuous dopaminergic delivery may widen patients' therapeutic window. Currently, this can be accomplished only with subcutaneous apomorphine or duodenal levodopa infusions. Apomorphine is a highly soluble agonist whose effect is similar to dopamine. Conversely, replacing whole oral therapy with levodopa infusion bypasses gastric emptying and avoids peaks and troughs in plasma by releasing levodopa in the duodenum/jejunum.
大多数帕金森病 (PD) 患者都会出现运动波动和运动障碍，这可能是由于黑质纹状体退行性过程导致多巴胺产生、储存和释放的变化所致。所有比较左旋多巴与多巴胺激动剂早期治疗的研究都表明，起始使用激动剂可降低运动并发症的风险——特别是运动障碍的风险——这可能是因为激动剂的半衰期更长，可提供持续的多巴胺能传递。在晚期 PD 患者中，从脉冲式到连续多巴胺能传递的转换可能会扩大患者的治疗窗口。目前，这只能通过皮下给予阿扑吗啡或十二指肠给予左旋多巴输注来实现。阿扑吗啡是一种高度可溶性的激动剂，其作用与多巴胺相似。相反，用左旋多巴输注替代整个口服治疗可以绕过胃排空，并通过在十二指肠/空肠中释放左旋多巴来避免血浆中的峰值和谷值。
