Orexin / Hypocretin
Orexin-A and orexin-B are two excitatory brain signals (neuropeptides). They are also called hypocretin-1 and hypocretin-2. A small cluster of neurons in your hypothalamus makes them. They were independently discovered in 1998. De Lecea and colleagues called them hypocretins (in PNAS). Sakurai and colleagues called them orexins (in Cell). They act on two receptors (OX1R and OX2R). And they project broadly to wake-promoting brain regions. Those include the locus coeruleus, the tuberomammillary nucleus, and the basal forebrain. The system stabilizes your wakefulness. It also gates the transitions between waking, NREM, and REM sleep. When you selectively lose your orexin neurons, usually through an autoimmune attack, you get narcolepsy type 1 (with cataplexy). And one drug class exploits this. 'DORAs' block both orexin receptors. Examples are suvorexant, lemborexant, and daridorexant. They are used to treat chronic insomnia.
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Sources
- De Lecea L, Kilduff TS, Peyron C, et al.. (1998). The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. *Proceedings of the National Academy of Sciences*doi:10.1073/pnas.95.1.322
- Sakurai T, Amemiya A, Ishii M, et al.. (1998). Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. *Cell*doi:10.1016/S0092-8674(00)80949-6
- Mogavero MP, Silvani A, Lanza G, DelRosso LM, Ferini-Strambi L. (2023). Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations. *Nature and Science of Sleep*doi:10.2147/NSS.S201994