Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease.
Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease.
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DOI：
10.1016/j.pharmthera.2011.07.004
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发表时间：
2011-12
影响因子：
13.5
通讯作者：
Franco, Rafael
中科院分区：
文献类型：
--
作者：
Armentero, Marie Therese;Pinna, Annalisa;Ferre, Sergi;Luis Lanciego, Jose;Mueller, Christa E.;Franco, Rafael
关键词：
腺苷A2A受体（A2AR）的几种选择性拮抗剂目前正在临床试验（I期至III期）中进行评估，以治疗帕金森病，它们可能很快就会进入市场。这些拮抗剂的有效性已经从研究中推导出来，这些研究证明了基底神经节中多巴胺D2和腺苷A2A受体之间的功能性相互作用。目前认为，A2AR拮抗剂可与多巴胺前体L-DOPA组合使用，以使帕金森病患者的运动症状最小化。然而，大量数据表明，除了改善运动症状外，腺苷A2AR拮抗剂还可以预防神经变性。尽管有这些有希望的迹象，一个进一步的问题必须考虑，以开发充分优化的抗帕金森病药物治疗，即存在的受体（异源）二聚体/寡聚体的G蛋白偶联受体，一个主题，目前激烈的争论的焦点在科学界。已知纹状体中表达的多巴胺D2受体（D2Rs）与A2A腺苷受体形成异聚体。因此，异源聚体特异性A2A受体拮抗剂的开发代表了用于鉴定更具选择性和更安全的药物的有希望的策略。
Several selective antagonists for adenosine A2A receptors (A2AR) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson’s disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D2 and adenosine A2A receptors in the basal ganglia. At present it is believed that A2AR antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson’s patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A2AR antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized anti-parkinsonian drug therapy, namely the existence of receptor (hetero)dimers/oligomers of G protein-coupled receptors, a topic currently the focus of intense debate within the scientific community. Dopamine D2 receptors (D2Rs) expressed in the striatum are known to form heteromers with A2A adenosine receptors. Thus, the development of heteromer-specific A2A receptor antagonists represents a promising strategy for the identification of more selective and safer drugs.
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DOI：
10.1038/npp.2008.144
发表时间：
2009-03
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Azdad K;Gall D;Woods AS;Ledent C;Ferré S;Schiffmann SN
通讯作者：
Schiffmann SN
影响因子：
3.6
作者：
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通讯作者：
Zimmer, Andreas
影响因子：
3.8
作者：
BARRACO, RA;MARTENS, KA;NORMILE, HJ
通讯作者：
NORMILE, HJ
影响因子：
15.9
作者：
Brochard, Vanessa;Combadiere, Behazine;Hunot, Stephane
通讯作者：
Hunot, Stephane
影响因子：
6.2
作者：
Brambilla, R;Cottini, L;Abbracchio, MP
通讯作者：
Abbracchio, MP