Current Pharmaceutical Design - Volume 14, Issue 15, 2008

Adenosine is an endogenous modulator which regulates many Central Nervous System (CNS) functions and which activities are mediated by the binding to four distinct G-protein-coupled receptors: the A1, A2A, A2B, and A3 adenosine receptor subtypes. In the last few years adenosine A2A receptors have been shown to play a significant role in different physiological and pathological processes in the brain. The aim of this iss Read More

Adenosine A2A-dopamine D2 receptor interactions play a very important role in striatal function. A2A-D2 receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagonistic interactions between A2A and D2 receptors in the same neurons, the GABAergic enkephalinergic neurons. An an Read More

Adenosine A2A receptors present in the central nervous system have been implicated in the modulation of motor functions. Accordingly, adenosine A2A receptor antagonists currently constitute an attractive non-dopaminergic option for use in the treatment of Parkinson's disease (PD). The highly enriched distributions of adenosine A2A receptors in striatopallidal neurons, and their ability to form functional heteromeric compl Read More

Over the past 5 years, the adenosine A2A receptor (A2AR) is emerging as an attractive therapeutic target for modulating brain injury in a variety of animal models of neurological disorders including stroke. The evidence we have to date indicates that both adenosine and A2A antagonists are neuroprotective in ischaemic brain injury. From drug development perspective, administering A2A antagonists in association with inhibito Read More

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by the expansion of a polymorphic CAG trinucleotide repeat encoding a poly-glutamine tract within the Huntingtin protein. GABAergic enkephalin neurons of the basal ganglia, which show the highest levels of expression of adenosine A2A receptors, are the most vulnerable in HD. Such a selective neuronal vulnerability, which occurs despite ubi Read More

The interest on targeting adenosine A2A receptors in the realm of psychiatric diseases first arose based on their tight physical and functional interaction with dopamine D2 receptors. However, the role of central A2A receptors is now viewed as much broader than just controlling D2 receptor function. Thus, there is currently a major interest in the ability of A2A receptors to control synaptic plasticity at glutamatergic s Read More

Since the discovery of the biological effects of adenosine, the development of potent and selective agonists and antagonists of adenosine receptors has been the subject of medicinal chemistry research for several decades, even if their clinical evaluation has been discontinued. Main problems include side effects due to the ubiquity of the receptors and the possibility of side effects, or to low brain penetration (in particular for th Read More