Neurodegenerative Diseases Research Centre, School of Health and Biomedical Sciences, King's College London, London, United Kingdom.
Mov Disord. 2010 Feb 15;25(3):377-84. doi: 10.1002/mds.22960.
Reduced expression of dyskinesia is observed in levodopa-primed MPTP-treated common marmosets when dopamine agonists are used to replace levodopa. We now investigate whether a combination of the D-2/D-3 agonist pramipexole and levodopa also reduces dyskinesia intensity while maintaining the reversal of motor disability. Drug naïve, non-dyskinetic MPTP-treated common marmosets were treated daily for up to 62 days with levodopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) or pramipexole (0.04-0.3 mg/kg BID) producing equivalent reversal of motor disability and increases in locomotor activity. Levodopa alone resulted in marked dyskinesia induction but little or no dyskinesia resulted from the administration of pramipexole. From day 36, some animals were treated with a combination of levodopa (3.125-6.25 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) and pramipexole (0.1-0.2 mg/kg p.o. SID). This improved motor disability to a greater extent than occurred with levodopa alone. Importantly, while dyskinesia was greater than that produced by pramipexole alone, the combination resulted in less intense dyskinesia than produced by levodopa alone. These results suggest that pramipexole could be administered with a reduced dose of levodopa to minimize dyskinesia in Parkinson's disease while maintaining therapeutic efficacy.
当使用多巴胺激动剂替代左旋多巴时，在接受左旋多巴预处理的 MPTP 处理的普通狨猴中观察到运动障碍的表达减少。我们现在研究 D2/D3 激动剂普拉克索与左旋多巴联合使用是否也能降低运动障碍的严重程度，同时保持运动障碍的逆转。在没有接受药物治疗、没有运动障碍的 MPTP 处理的普通狨猴中，每天接受左旋多巴（12.5mg/kg 加卡比多巴 12.5mg/kg 口服 BID）或普拉克索（0.04-0.3mg/kg BID）治疗，持续长达 62 天，这两种药物都能产生等效的运动障碍逆转和运动活动增加。左旋多巴单独使用会导致明显的运动障碍诱导，但普拉克索的使用几乎不会导致运动障碍。从第 36 天开始，一些动物接受了左旋多巴（3.125-6.25mg/kg 加卡比多巴 12.5mg/kg 口服 BID）和普拉克索（0.1-0.2mg/kg 口服 SID）的联合治疗。这比单独使用左旋多巴更能显著改善运动障碍。重要的是，虽然运动障碍比单独使用普拉克索更严重，但联合治疗产生的运动障碍比单独使用左旋多巴产生的运动障碍不那么严重。这些结果表明，普拉克索可以与较低剂量的左旋多巴联合使用，以最大限度地减少帕金森病中的运动障碍，同时保持治疗效果。
