在帕金森病动物模型中，氘取代的左旋多巴显示出增加的行为效力和多巴胺输出：与左旋多巴和 MAO-B 抑制剂产生的效果进行比较。,Journal of Neural Transmission

当前位置： X-MOL 学术 › J. Neural. Transm. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

在帕金森病动物模型中，氘取代的左旋多巴显示出增加的行为效力和多巴胺输出：与左旋多巴和 MAO-B 抑制剂产生的效果进行比较。
Journal of Neural Transmission ( IF 3.2 ) Pub Date : 2014-06-07 , DOI: 10.1007/s00702-014-1247-6
Torun Malmlöf ₁ , Kristin Feltmann , Åsa Konradsson-Geuken , Frank Schneider , Rudolf-Giesbert Alken , Torgny H Svensson , Björn Schilström

Affiliation

帕金森病 (PD) 的最有效治疗方法 L-DOPA 与主要副作用有关，尤其是 L-DOPA 引起的运动障碍，这促使开发新的治疗策略。我们之前已经表明，与 L-DOPA 相比，用显着较低剂量的氘代 L-DOPA (D3-L-DOPA) 进行慢性治疗，在 6-OHDA 损伤的大鼠中产生了相同的抗帕金森病作用并减少了运动障碍。D3-L-DOPA 的优势很可能与单胺氧化酶 (MAO) 对氘多巴胺的代谢减少有关。因此，这里进行了比较神经化学分析，研究了 D3-L-DOPA 和 L-DOPA 对使用体内微透析的 6-OHDA 损伤动物的多巴胺输出和代谢的影响。另外，将 D3-L-DOPA 和 L-DOPA 单独产生的作用与药物与 MAO-B 抑制剂司来吉兰联合用于 PD 治疗时产生的作用进行比较。首先评估不同治疗组合的运动激活；在这里，与 L-DOPA 相比，D3-L-DOPA 增加的效力得到证实并显示出与司来吉兰/L-DOPA 组合产生的效果具有同等程度。与左旋多巴给药相比，D3-左旋多巴和司来吉兰/左旋多巴给药后多巴胺的细胞外水平也增加。D3-L-DOPA 和司来吉兰/L-DOPA 的组合产生的增强的行为和神经化学作用归因于 MAO-B 释放的多巴胺代谢减少。D3-L-DOPA 和司来吉兰/L-DOPA 产生的类似作用，

"点击查看英文标题和摘要"

Deuterium-substituted L-DOPA displays increased behavioral potency and dopamine output in an animal model of Parkinson's disease: comparison with the effects produced by L-DOPA and an MAO-B inhibitor.

The most effective treatment of Parkinson's disease (PD) L-DOPA is associated with major side effects, in particular L-DOPA-induced dyskinesia, which motivates development of new treatment strategies. We have previously shown that chronic treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L-DOPA), compared with L-DOPA, produced equal anti-parkinsonian effect and reduced dyskinesia in 6-OHDA-lesioned rats. The advantageous effects of D3-L-DOPA are in all probability related to a reduced metabolism of deuterium dopamine by the enzyme monoamine oxidase (MAO). Therefore, a comparative neurochemical analysis was here performed studying the effects of D3-L-DOPA and L-DOPA on dopamine output and metabolism in 6-OHDA-lesioned animals using in vivo microdialysis. The effects produced by D3-L-DOPA and L-DOPA alone were additionally compared with those elicited when the drugs were combined with the MAO-B inhibitor selegiline, used in PD treatment. The different treatment combinations were first evaluated for motor activation; here the increased potency of D3-L-DOPA, as compared to that of L-DOPA, was confirmed and shown to be of equal magnitude as the effect produced by the combination of selegiline/L-DOPA. The extracellular levels of dopamine were also increased following both D3-L-DOPA and selegiline/L-DOPA administration compared with L-DOPA administration. The enhanced behavioral and neurochemical effects produced by D3-L-DOPA and the combination of selegiline/L-DOPA are attributed to decreased metabolism of released dopamine by MAO-B. The similar effect produced by D3-L-DOPA and selegiline/L-DOPA, respectively, is of considerable clinical interest since D3-L-DOPA, previously shown to exhibit a wider therapeutic window, in addition may reduce the need for adjuvant MAO-B inhibitor treatment.

更新日期：2019-11-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南