摘要
目前对帕金森病的药物治疗是相当不足的,近期需要改良的治疗剂。腺苷酸A2A受体和单胺氧化酶(MAO)B是抗帕金森病治疗性化合物设计的两个重要分子靶点。腺苷酸A2A受体拮抗剂是一类相对新的抗帕金森病制剂,通过多巴胺D2受体促进多巴胺介导的神经传递而起作用。MAO-B抑制剂已经被确定为帕金森病的治疗方法,并且可以抑制脑内MAO-B催化的多巴胺代谢物。这种保存减少了多巴胺的含量,并且扩展了多巴胺的作用。A2A拮抗剂和MAO-B抑制剂也与神经保护作用相关,进一步确定了帕金森病中这类化合物的作用。有趣的是,作为一种已知的腺苷受体拮抗剂咖啡因,近期被认为是A2A拮抗剂和MAO-B抑制剂设计与发现的先导化合物。这篇综述总结了发现咖啡因源MAO-B抑制剂近期所做的努力。前期对咖啡因源A2A拮抗剂的设计进行了广泛的综述。对在两个靶点作用的双靶点化合物的发现前景也进行了评估。阻断A2A受体和MAO-B激活和功能的化合物在治疗帕金森病患者方面也许起到协同作用。
关键词: 腺苷酸A2A 受体,咖啡因,药物设计,双靶向,抑制剂,单胺氧化酶,帕金森病
Current Medicinal Chemistry
Title:Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease
Volume: 22 Issue: 8
Author(s): Jacobus P. Petzer and Anel Petzer
Affiliation:
关键词: 腺苷酸A2A 受体,咖啡因,药物设计,双靶向,抑制剂,单胺氧化酶,帕金森病
摘要: The current pharmacological therapies for the treatment of Parkinson’s disease are mostly inadequate and recent, improved therapeutic agents are required. Two important molecular targets for the design of anti-parkinsonian therapeutic compounds are the adenosine A2A receptor and the enzyme, monoamine oxidase (MAO) B. Adenosine A2A receptor antagonists are a relatively new class of anti-parkinsonian agents, which act by potentiating dopamine-mediated neurotransmission via dopamine D2 receptors. MAO-B inhibitors are established therapy of Parkinson’s disease and inhibit the MAO-B-catalysed metabolism of dopamine in the brain. This conserves reduced dopamine stores and extends the action of dopamine. A2A antagonism and MAO-B inhibition have also been associated with neuroprotective effects, further establishing roles for these classes of compounds in Parkinson’s disease. Interestingly, caffeine, a known adenosine receptor antagonist, has been recently considered as a lead compound for the design and discovery of A2A antagonists and MAO-B inhibitors. This review summarizes the recent efforts to discover caffeinederived MAO-B inhibitors. The design of caffeine-derived A2A antagonists has been extensively reviewed previously. The prospect of discovering dual-target-directed compounds that act at both targets is also evaluated. Compounds that block the activation and function of both A2A receptors and MAO-B may have a synergistic effect in the treatment of patients with Parkinson’s disease.
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Jacobus P. Petzer and Anel Petzer , Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease, Current Medicinal Chemistry 2015; 22 (8) . https://dx.doi.org/10.2174/0929867322666141215160015
DOI https://dx.doi.org/10.2174/0929867322666141215160015 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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