Behavioral Neuroscience Program, Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA.
J Neural Transm (Vienna). 2018 Aug;125(8):1203-1216. doi: 10.1007/s00702-017-1837-1. Epub 2018 Jan 5.
Dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) continues to be the gold-standard treatment for Parkinson's disease (PD). Despite clear symptomatic benefit, long-term L-DOPA use often results in the development of L-DOPA-induced dyskinesia (LID), significantly reducing quality of life and increasing costs for PD patients and their caregivers. Accumulated research has demonstrated that several pre- and post-synaptic mechanisms contribute to LID development and expression. In particular, raphe-striatal hyperinnervation and unregulated DA release from 5-HT terminals is postulated to play a central role in LID manifestation. As such, manipulation of the 5-HT system has garnered considerable attention. Both pre-clinical and clinical research has supported the potential of modulating the 5-HT system for LID prevention and treatment. This review discusses the rationale for continued investigation of several potential anti-dyskinetic strategies including 5-HT stimulation of 5-HT1A and 5-HT1B receptors and blockade of 5-HT2A receptors and SERT. We present the latest findings from experimental and clinical investigations evaluating these 5-HT targets with the goal of identifying those with translational promise and the challenges associated with each.
用 L-3,4-二羟基苯丙氨酸（L-DOPA）进行多巴胺（DA）替代疗法仍然是治疗帕金森病（PD）的金标准。尽管有明显的症状改善，但长期使用 L-DOPA 常常导致 L-DOPA 诱导的运动障碍（LID）的发展，显著降低 PD 患者及其护理人员的生活质量并增加成本。积累的研究表明，几种突触前和突触后机制有助于 LID 的发展和表达。特别是，中缝-纹状体过度神经支配和 5-HT 末梢不受调节的 DA 释放被认为在 LID 表现中起核心作用。因此，对 5-HT 系统的操纵引起了相当大的关注。临床前和临床研究都支持调节 5-HT 系统预防和治疗 LID 的潜力。这篇综述讨论了继续研究几种潜在的抗运动障碍策略的理由，包括 5-HT1A 和 5-HT1B 受体的刺激和 5-HT2A 受体和 SERT 的阻断。我们介绍了评估这些 5-HT 靶点的最新实验和临床研究结果，目的是确定那些具有转化前景的靶点和每个靶点所面临的挑战。
