腺苷A2A拮抗剂与帕金森病。

International review of neurobiology Pub Date : 2023-01-01 Epub Date: 2023-07-03 DOI:10.1016/bs.irn.2023.06.004
Michelle Offit, Brian Nagle, Gonul Ozay, Irma Zhang, Anastassia Kerasidis, Yasar Torres-Yaghi, Fernando Pagan
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摘要

尽管目前还没有治愈帕金森病(PD)的方法,但有几类具有不同作用机制的药物可以帮助改善帕金森病患者的功能。多巴胺衍生物是帕金森病的一线疗法,因此多巴胺受体激动剂(DA)已被证明可以改善PD患者的症状功能。帕金森病治疗中多巴胺激动剂药物的两种主要配方是麦角碱和非麦角碱衍生物。此外,研究表明,帕金森病可能涉及其他神经递质的异常,如乙酰胆碱、去甲肾上腺素和血清素,因此非多巴胺能药物在帕金森病管理中也至关重要。实例包括NMDA受体拮抗剂、多巴胺拮抗剂(即神经抑制剂)、乙酰胆碱受体拮抗剂,5-羟色胺受体2A激动剂和腺苷A2拮抗剂。一般来说,多巴胺能药物在改善帕金森病的运动参与方面最有效,而非多巴胺能药物往往侧重于帕金森病的非运动参与。在本章中,我们将重点介绍多巴胺能与非多巴胺能治疗的化学和药物背景,最后重点介绍腺苷A2拮抗剂。
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Adenosine A2A antagonists and Parkinson's disease.

Although there is no cure for Parkinson's disease (PD), there are several classes of medications with various mechanisms of action that can help improve the functionality of someone with PD. Dopamine derivatives are first line therapies for PD, hence dopamine receptor agonists (DAs) have been shown to improve functionality of symptoms in PD patients. The two main formulations of dopamine agonist medications in PD therapy are ergoline and non-ergoline derivatives. Additionally, it has been shown that PD can involve irregularities in other neurotransmitters, such as acetylcholine, norepinephrine, and serotonin, hence why non-dopaminergic medications are also vital in PD management. Examples include NMDA receptor antagonists, dopamine antagonists (i.e. neuroleptics), acetylcholine receptor antagonists, serotonin receptor 2A agonists, and adenosine A2 antagonists. In general, dopaminergic medications are the most effective in improving motor involvement with PD, whereas non-dopaminergic medications tend to focus on the non-motor involvement of PD. In this chapter, we will focus on the chemistry and medication background on dopaminergic vs non-dopaminergic therapy, with a focus of adenosine A2 antagonists at the end.

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A general clinical overview of the non-motor symptoms in Parkinson's disease: Neuropsychiatric symptoms. Executive dysfunction and cognitive decline, a non-motor symptom of Parkinson's disease captured in animal models. Insight gained from using animal models to study pain in Parkinson's disease. Investigating affective neuropsychiatric symptoms in rodent models of Parkinson's disease. Macro and micro-sleep dysfunctions as translational biomarkers for Parkinson's disease.
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