Adenosine A2A receptors and sleep

Adenosine, a known endogenous somnogen, induces sleep via A1 and A2A receptors. In this chapter, we review the current knowledge regarding the role of the adenosine A2A receptor and its agonists, antagonists, and allosteric modulators in sleep-wake regulation. Although many adenosine A2A receptor agonists, antagonists, and allosteric modulators have been identified, only a few have been tested to see if they can promote sleep or wakefulness. In addition, the growing popularity of natural sleep aids has led to an investigation of natural compounds that may improve sleep by activating the adenosine A2A receptor. Finally, we discuss the potential therapeutic advantage of allosteric modulators of adenosine A2A receptors over classic agonists and antagonists for treating sleep and neurologic disorders.