谷氨酸拮抗剂的抗帕金森作用-单独和与左旋多巴:对可能机制的证据和建议的回顾。

M S Starr
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引用次数: 61

摘要

最近有很多关于谷氨酸受体拮抗剂是否可以用于对抗帕金森病的运动困难的猜测,无论是作为单一疗法,还是作为综合疗法来增强传统左旋多巴治疗的效果。后者似乎是更实用的方法,这种治疗的治疗意义已被详细讨论。然而,谷氨酸拮抗剂增强左旋多巴抗帕金森作用的机制仍不清楚。在这篇综述中,我们探索了证据,并考虑了使用NMDA和非NMDA受体阻滞剂治疗帕金森病的实用性,以及关注多巴胺和谷氨酸系统之间的行为协同作用可能在细胞水平上产生的方式。人们特别关注谷氨酸拮抗剂与突触后多巴胺D1和D2接受机制之间的差异相互作用,因为目前认为这些相互作用反映了基底节区两个主要输出回路的活动:所谓的直接通路到黑质和间接通路到白球。最后,我们考虑了新的建议,即抑制基底神经节中的谷氨酸传递会加速左旋多巴在突触前位点向多巴胺的酶转化。
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Antiparkinsonian actions of glutamate antagonists--alone and with L-DOPA: a review of evidence and suggestions for possible mechanisms.

There has been much speculation of late as to whether antagonists of glutamate receptors can be used to combat the motor difficulties of Parkinson's disease, either as monotherapy, or as polytherapy to boost the effects of conventional L-DOPA treatment. The latter seems to be the more practical approach and the therapeutic implications of such treatment have been discussed in some detail. However, the mechanisms by which glutamate antagonists potentiate the antiparkinsonian actions of L-DOPA, remain cryptic. In this review we have explored the evidence and considered the practicality of using NMDA and non-NMDA receptor blockers to treat parkinsonism, as well as focusing on the ways in which the behavioural synergy between dopamine and glutamate systems could conceivably arise at the cellular level. Particular attention has been paid to the differential interaction between glutamate antagonists and postsynaptic dopamine D1 and D2 receptory mechanisms, since these are currently believed to reflect the activity of the two major basal ganglia output circuits: the so-called direct pathway to the substantia nigra and the indirect pathway to the globus pallidus. Finally, we have considered the new proposal, that inhibiting glutamate transmission in the basal ganglia accelerates the enzymic conversion of L-DOPA to dopamine at presynaptic sites.

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