Adenosin A_2A Rezeptorantagonisten als Therapieoption beim idiopathischen Parkinson-Syndrom?

 

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Zusammenfassung

Beim Parkinson-Syndrom wurde sich lange Zeit auf die motorischen Symptome und die Therapie mit dopaminergen Substanzen fokussiert. In den letzten Jahren gewannen die nicht-motorischen Symptome immer mehr Bedeutung, da sie früh im Krankheitsverlauf auftreten und die Lebensqualität erheblich einschränken. Dadurch wurde aber auch die Notwendigkeit einer Behandlung nicht nur des dopaminergen Defizits offensichtlich. Als weitere therapeutische Option wurden die Adenosin A_2A Rezeptorantagonisten entwickelt, da Adenosin A_2A Rezeptorantagonisten nicht-dopaminerg und selektiv in den Basalganglien lokalisiert sind. Somit besteht die Möglichkeit striato-thalamo-kortikalen Schleifen zusätzlich zu modulieren. Bereits 2013 wurde ein Adenosin A_2A Rezeptorantagonist in Japan und in 2019 in den USA als Add-on zu L-DOPA zugelassen. Mit einer Zulassung in Europa wird in naher Zukunft gerechnet. In dieser Übersicht möchten wir die theoretischen Grundlagen dieses Therapieansatzes darstellen und die aktuellen Daten zur Wirksamkeit und dem therapeutischen Einsatz referieren.

Abstract

In Parkinson’s disease, the focus has long been on motor symptoms and therapy with dopaminergic substances. In recent years, the importance of non-motor symptoms has been increasingly recognized, as they occur early in the course of the disease and restrict considerably the quality of life. However, this also made the need for treatment of non-dopaminergic deficits obvious. Adenosine A_2A receptor antagonists were identified as an additional therapy, since the adenosine A_2A receptors are non-dopaminergic and selectively localized in the basal ganglia. This means that the striato-thalamo-cortical loops can be modulated. An adenosine A_2A receptor antagonist was already approved in Japan in 2013 and in the USA in 2019 as an add-on to L-DOPA. Approval for this drug in Europe is expected in the near future. In this overview, we present the theoretical basis and current data on its efficacy and therapeutic use.

Publication History

Received: 10 September 2021

Accepted: 06 December 2021

Article published online:
28 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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