In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives:: Implications for Parkinson's Disease
In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives:: Implications for Parkinson's Disease
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DOI：
10.1016/j.ejphar.2008.05.013
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发表时间：
2008-07-28
影响因子：
5
通讯作者：
Dajas, Federico
中科院分区：
文献类型：
--
作者：
Abin-Carriquiry, J. Andres;Costa, Gustavo;Dajas, Federico
烟碱乙酰胆碱受体激动剂被认为是治疗帕金森病的潜在药物，因为它们能够改善实验性帕金森症状，减少 3,4-二羟基-L-苯丙氨酸引起的运动障碍，并在实验水平上阻止神经退行性过程。在目前的工作中，通过微透析在体内表征了烟碱激动剂金雀花碱和两种卤化衍生物（3-溴金雀花碱和5-溴金雀花碱）诱导纹状体多巴胺释放的能力。金雀花碱、5-溴金雀花碱和尼古丁在通过微透析探针进行局部应用时，在引发多巴胺释放方面比 3-溴金雀花碱更有效。此外，在黑质内注射 6-羟基多巴胺 (6-OHDA) 之前和之后间歇性施用激动剂，并在病变后 8 天评估纹状体多巴胺组织水平。金雀花碱及其 5-溴衍生物（但不是 3-溴衍生物）均显着阻止 6-OHDA 诱导的纹状体多巴胺组织水平的降低。这些结果表明烟碱激动剂通过突触前烟碱受体刺激体内多巴胺释放的功效可能与其诱导纹状体保护的潜力有关。 (C) 2008 Elsevier B.V. 保留所有权利。
Nicotinic acetylcholine receptor agonists are considered potential pharmacological agents for Parkinson's Disease treatment, due to their ability to improve experimental Parkinson symptomatology, reduce 3,4-dihydroxy-L-phenylalanine-incluced clyskinesias and stop the neurodegenerative process at an experimental level. In the present work, the ability of the nicotinic agonistcytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to induce striatal dopamine release was characterized in vivo by microdialysis. Cytisine, 5-bromocytisine and nicotine were much more efficacious than 3-bromocytisine in eliciting dopamine release in response to their local application through the microdialysis probe. Moreover, the agonists were intermittently administered before and after an intranigral injection of 6-hydroxydopamine (6-OHDA), and striatal dopamine tissue levels were assessed 8 days after the lesion. Both cytisine and its 5-bromo derivative (but not the 3-bromo derivative) significantly prevented the decrease of striatal dopamine tissue levels induced by 6-OHDA. These results suggest that the efficacy of nicotinic agonists to stimulate dopamine release in vivo through presynaptic nicotinic receptors could be related to their potential to induce striatal protection. (C) 2008 Elsevier B.V. All rights reserved.