Adenosine, neurodegeneration and neuroprotection.

Protection against neuronal damage is a major objective of current research in areas such as stroke medicine, Alzheimer's disease and other neurodegenerative conditions. Adenosine receptors are important modulators of cell survival, and thus agents targeting these receptors could be valuable therapeutic agents. Agonists at A(1) receptors and antagonists at A(2A) receptors are known to protect acutely against neuronal damage caused by toxins or ischemia-reperfusion, and these compounds can also protect against the cell damage inflicted by reactive oxygen species. Even endogenous adenosine may be neuroprotective, since its levels rise substantially in association with a period of ischemia-reperfusion. Unfortunately, there is growing evidence that the efficacy of adenosine receptor activation can be reduced by the concomitant activation of glutamate receptors responding to N-methyl-D-aspartate (NMDA), probably acting via the release of nitric oxide. Such problems will need to be resolved before adenosine receptor agonists can proceed far as neuroprotective agents. The use of receptor antagonists may prove a more valuable approach.