兴奋性氨基酸在帕金森病实验模型中的作用。

K Ossowska
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引用次数: 93

摘要

本文的目的是回顾最近关于兴奋性氨基酸在帕金森病和帕金森症状的动物等效物中的作用的文献。分析NMDA和AMPA拮抗剂对利血平诱导的运动障碍、猝倒和僵直、抗精神病药诱导的猝倒、6- ohda损伤大鼠的翻身行为以及MPTP引起的猴子帕金森症状的影响。此外,还讨论了NMDA拮抗剂在帕金森病中的作用。还介绍了这些药物对甲基苯丙胺、MPTP和6-OHDOPA退行性质的保护作用的数据。基于以上研究结果,可以得出以下结论:(1)脑内谷氨酸传递紊乱似乎在帕金森病症状的发展中起重要作用;(2) nmda受体阻断成分可能对抗帕金森药物的治疗效果做出实质性贡献;到目前为止,ampa受体阻断成分的类似贡献尚未得到充分的证明;(3)阻断NMDA受体的化合物可能预防帕金森病的发展;然而,这一假设需要进一步的研究;(4) NMDA受体拮抗剂的副作用可能是限制人类使用这些化合物的一个因素。
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The role of excitatory amino acids in experimental models of Parkinson's disease.

The aim of this article was to review the recent literature on the role of excitatory amino acids in Parkinson's disease and in animal equivalents of parkinsonian symptoms. Effects of NMDA and AMPA antagonists on the reserpine-induced akinesia, catalepsy and rigidity, on the neuroleptic-induced catalepsy, on the turning behaviour of 6-OHDA-lesioned rats, as well as on the parkinsonian symptoms evoked by MPTP in monkeys were analysed. Moreover, the role of NMDA antagonists in Parkinson's disease was discussed. Data concerning the protective influence of these drugs on degenerative properties of methamphetamine, MPTP and 6-OHDOPA were also presented. On the basis of the above findings, the following conclusions may be drawn: (1) disturbances in the glutamatergic transmission in various brain structures seem to play a significant role in the development of symptoms of Parkinson's disease; (2) the NMDA-receptor blocking component may make a substantial contribution to the therapeutic effect of antiparkinsonian drugs; a similar contribution of AMPA-receptor blocking component has not been sufficiently documented, so far; (3) compounds blocking NMDA receptors may possibly prevent the development of Parkinson's disease; this presumption needs, however further studies; (4) side effects of NMDA receptor antagonists may be a limiting factor in the use of these compounds in humans.

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