An Update on Adenosine A(2A) Receptors as Drug Target in Parkinson's Disease

作者：Vallano Antoni; Fernandez Duenas Victor; Pedros Consuelo; Maria Arnau Josep; Ciruela Francisco^*

来源：CNS & Neurological Disorders-Drug Targets, 2011, 10(6): 659-669.

• Adenosine A(2A) receptors
• Parkinson's disease
• GPCR oligomerization
• Clinical trial
• Istradefylline
• preladenant

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A(2A) receptors (A(2A)Rs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D-2 receptor (D2R). Furthermore, it is assumed that the formation of balanced A(2A)R/D2R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A(2A)R activation reduces the affinity of striatal D2R for dopamine and the blockade of A(2A)R with specific antagonists facilitates function of the D2R. Thus, it may be postulated that A(2A)R antagonists are pro-dopaminergic agents. Therefore, A(2A)R antagonists will potentially reduce the effects associated with dopamine depletion in Parkinson's disease (PD). Accordingly, this class of compounds have recently attracted considerable attention as potential therapeutic agents for PD pharmacotherapy as they have shown potential effectiveness in counteracting motor dysfunctions and also displayed neuroprotective and anti-inflammatory effects in animal models of PD. Overall, we provide here an update of the current state of the art of these A(2A)R-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

• 出版日期2011-9