Adenosine

Adenosine is a purine nucleoside that accumulates in the brain during wakefulness as a byproduct of neuronal energy metabolism and acts on A1 and A2A receptors to promote sleepiness and suppress arousal, serving as the primary molecular mediator of homeostatic sleep pressure. Its levels are highest after prolonged waking and decline during sleep. Caffeine exerts its alerting effects principally by competitively blocking adenosine receptors without depleting adenosine itself, which is why the sleepiness rebound after caffeine clearance is pronounced. Beyond sleep regulation, adenosine is involved in cerebrovascular autoregulation and has been implicated in the glymphatic clearance process that intensifies during slow-wave sleep.