How and why the adenosine A 2A receptor became a target for Parkinson's disease therapy.

Autor: Jenner P; Institute of Pharmaceutical Sciences, King's College London, London, United Kingdom. Electronic address: peter.jenner@kcl.ac.uk., Kanda T; Kyowa Kirin Co., Ltd., Otemachi. Chiyoda-ku, Tokyo, Japan., Mori A; SNLD Ltd., Akashi-sho, Chuo-ku, Tokyo, Japan.
Jazyk: angličtina
Zdroj: International review of neurobiology [Int Rev Neurobiol] 2023; Vol. 170, pp. 73-104. Date of Electronic Publication: 2023 May 14.
DOI: 10.1016/bs.irn.2023.04.005
Abstrakt: 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 2A 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 2A 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 2A 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.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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