Adenosine A2A receptors and sleep.

Adenosine, a known endogenous somnogen, induces sleep via A₁ and A_2A receptors. In this chapter, we review the current knowledge regarding the role of the adenosine A_2A receptor and its agonists, antagonists, and allosteric modulators in sleep-wake regulation. Although many adenosine A_2A 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 A_2A receptor. Finally, we discuss the potential therapeutic advantage of allosteric modulators of adenosine A_2A receptors over classic agonists and antagonists for treating sleep and neurologic disorders.