Institute of Pharmaceutical Sciences, King's College London, London, United Kingdom.
Kyowa Kirin Co., Ltd., Otemachi. Chiyoda-ku, Tokyo, Japan.
Int Rev Neurobiol. 2023;170:73-104. doi: 10.1016/bs.irn.2023.04.005. Epub 2023 May 14.
Dopaminergic therapy for Parkinson's disease has revolutionised the treatment of the motor symptoms of the illness. However, it does not alleviate all components of the motor deficits and has only limited effects on non-motor symptoms. For this reason, alternative non-dopaminergic approaches to treatment have been sought and the adenosine A receptor provided a novel target for symptomatic therapy both within the basal ganglia and elsewhere in the brain. Despite an impressive preclinical profile that would indicate a clear role for adenosine A antagonists in the treatment of Parkinson's disease, the road to clinical use has been long and full of difficulties. Some aspects of the drugs preclinical profile have not translated into clinical effectiveness and not all the clinical studies undertaken have had a positive outcome. The reasons for this will be explored and suggestions made for the further development of this drug class in the treatment of Parkinson's disease. However, one adenosine A antagonist, namely istradefylline has been introduced successfully for the treatment of late-stage Parkinson's disease in two major areas of the world and has become a commercial success through offering the first non-dopaminergic approach to the treatment of unmet need to be introduced in several decades.
多巴胺能疗法治疗帕金森病已经彻底改变了这种疾病运动症状的治疗方式。然而，它并不能缓解运动障碍的所有组成部分，对非运动症状的影响也有限。因此，人们一直在寻找替代的非多巴胺能治疗方法，而腺苷 A 受体为基底神经节和大脑其他区域的症状治疗提供了一个新的靶点。尽管令人印象深刻的临床前特征表明腺苷 A 拮抗剂在治疗帕金森病方面具有明确的作用，但通往临床应用的道路漫长而充满困难。一些药物临床前特征并未转化为临床疗效，并非所有进行的临床研究都有积极的结果。本文将探讨这些原因，并为进一步开发这类药物治疗帕金森病提出建议。然而，一种名为伊曲茶碱的腺苷 A 拮抗剂已在世界两个主要地区成功用于治疗晚期帕金森病，并通过提供几十年来首次针对未满足需求的非多巴胺能治疗方法取得商业成功。
