A pair of neuropeptides — orexin-A and orexin-B (hypocretin-1/2) — from a small cluster of lateral-hypothalamic neurons whose projections keep wakefulness switched on and stable.
It was discovered independently by two groups in 1998: Luis de Lecea's team named them hypocretins (PNAS, January 1998); Takeshi Sakurai and Masashi Yanagisawa's team named them orexins (Cell, February 1998). Orexin-A is hypocretin-1, orexin-B is hypocretin-2.
The two orexin receptors. OX1R binds orexin-A preferentially; OX2R binds both peptides. They sit on arousal centres across the brain, and OX2R in particular anchors stable wakefulness.
Narcolepsy type 1. Human patients selectively lose the orexin neurons (85–95%), shown in 2000 by Peyron et al. (Nature Medicine) and Thannickal et al. (Neuron); the animal proof came in 1999 from an OX2R mutation in narcoleptic dogs (Lin et al., Cell) and orexin knockout mice (Chemelli et al., Cell).
Blocking orexin receptors lets sleep arrive, so dual orexin receptor antagonists (DORAs) treat insomnia: suvorexant (Merck, 2014), lemborexant (Eisai, 2019) and daridorexant (Idorsia, 2022) are all FDA-approved.
Takeda's oral, OX2R-selective orexin agonist for narcolepsy type 1: positive phase 2 in NEJM (May 2025), phase 3 FirstLight and RadiantLight completed in 2025, and an FDA priority-review application accepted in February 2026 with a decision expected in Q3 2026.
Takeda's first oral orexin agonist: it improved wakefulness in phase 2 but was halted in October 2021 after a liver-safety signal (full account in NEJM 2023). The mechanism was vindicated and the programme continued with oveporexton.
Panacea Bio Chem, led by biochemist and AAC designer Bogdan Dicoias, runs a research programme in peptide agonist design for the orexin receptors, disclosed at concept level — no compound, assay result or clinical claim is made on this site. The credited timeline is on The Research.