Levodopa therapy
Levodopa therapy
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左旋多巴疗法
DOI：
10.1212/wnl.50.5_suppl_5.s17
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发表时间：
1998
期刊：
影响因子：
9.9
通讯作者：
T. Chase
中科院分区：
文献类型：
--
作者：
T. Chase
正常的运动功能依赖于从黑质投射到纹状体的神经元高度调节的递质多巴胺的合成和释放。帕金森病涉及这些神经元的进行性变性。其核心症状是纹状体突触内多巴胺不足的直接后果。左旋多巴是治疗PD的标准护理，在其转化为多巴胺后通过恢复纹状体多巴胺能传递发挥作用。然而，正常运作的多巴胺系统和标准左旋多巴治疗提供的功能恢复之间存在显着差异。越来越多的临床和临床前证据表明，由当前治疗方案引起的多巴胺受体的间歇性刺激有助于最终影响大多数帕金森病患者的反应并发症。现在看来，纹状体GABA能神经元上的多巴胺能受体的慢性非生理刺激激活特征性信号传导通路，导致N-甲基-D-天冬氨酸（NMDA）亚型的相邻多巴胺能受体的突触功效增强。结果，这些GABA能传出神经元的功能以有利于运动并发症出现的方式改变。可以想象，使用多巴胺替代策略，提供更连续的多巴胺受体刺激将起到预防或减轻这些致残并发症。目前正在制定实现这一目标的一些有希望的办法。
Normal motor function is dependent on the highly regulated synthesis and release of the transmitter dopamine by neurons projecting from the substantia nigra to the corpus striatum. Parkinson's disease involves the progressive degeneration of these neurons. Its core symptoms are a direct consequence of a striatal insufficiency of intrasynaptic dopamine. Levodopa, the standard of care for the treatment of PD, acts after its conversion to dopamine by restoring striatal dopaminergic transmission. However, there are significant differences between the normally functioning dopamine system and the restoration of function provided by standard levodopa treatment. Increasing clinical and preclinical evidence suggests that the intermittent stimulation of dopamine receptors resulting from current therapeutic regimens contributes to the response complications that ultimately affect most parkinsonian patients. It now appears that chronic nonphysiologic stimulation of dopaminergic receptors on striatal GABAergic neurons activates characteristic signaling pathways, leading to a potentiation of the synaptic efficacy of adjacent glutamatergic receptors of the N-methyl-D-aspartate(NMDA) subtype. As a result, function of these GABAergic efferent neurons changes in ways that favor the appearance of motor complications. Conceivably, use of dopaminomimetic replacement strategies that provide more continuous dopamine receptor stimulation will act to prevent or alleviate these disabling complications. A number of promising approaches to achieving this goal are now under development.
影响因子：
158.5
作者：
SHOULSON, I;FAHN, S;PELUSIO, RM
通讯作者：
PELUSIO, RM