Frontiers in CNS Drug Discovery

Volume: 1

Indexed in: Scopus, EMBASE, Book Citation Index, Science Edition, BIOSIS Previews.

“Frontiers in CNS Drug Discovery” is an eBook series devoted to publishing the latest and the most important advances in Central Nervous System (CNS) drug design and discovery. Eminent scientists ...
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Blocking Striatal Adenosine A2A Receptors: A New Strategy for Basal Ganglia Disorders

Pp. 304-341 (38)

Christa E. Muller and Sergi Ferre


Adenosine A2A receptors are highly concentrated in the striatum, where they play an important modulatory role of glutamatergic transmission to the GABAergic enkephalinergic neuron, whose function is particularly compromised in Parkinson's disease and in the early stages of Huntington's disease. An important amount of preclinical data suggested the possible application of A2A receptor antagonists in Parkinson's disease, particularly as adjuvant therapy to the currently used dopaminergic agonists. Several A2A receptor antagonists are currently in clinical trials in patients with Parkinson's disease and initial results have been promising. In recent years, many pharmaceutical companies have started programs to develop A2A antagonists for Parkinson's disease and for other indications, such as neurodegenerative diseases in general, depression, and restless legs syndrome. Antagonists with high A2A receptor affinity and selectivity have been developed from various chemical classes of compounds, including xanthines, adenines and other amino-substituted heterocyclic compounds. Novel structures include benzothiazole and thiazolopyridine derivatives. The present review describes properties of standard A2A receptor antagonists including those in clinical development. Furthermore, the different chemical classes of A2A receptor antagonists that have been described in the literature, including recent patent literature, will be presented.


denosine, xanthines, adenine derivative, adenine analog, Parkinson's disease, adenosine receptor, antagonist, istradefylline, A2A receptor, pharmacophore model


PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Germany