Tryptamine from wake-active monoaminergic neurons regulates sleep homeostasis

Nature Neuroscience, Published online: 19 June 2026; doi:10.1038/s41593-026-02332-x

Cao et al. identify tryptamine as a sleep signal in mice. Wake-active monoaminergic neurons release tryptamine, which binds to GPR139 in POA neurons that suppress wake-promoting neurons. GPR139 agonists could be a new class of sleep medication.