Orexin-A
Orexin-A (hypocretin-1)
Also known as: Hypocretin-1
The wakefulness neuropeptide, sold as a nasal spray for alertness after a primate study showed intranasal delivery reversed sleep-deprivation deficits; no human efficacy trial exists and approved narcolepsy drugs use small molecules instead.
Overview
Orexin-A regulates arousal through OX1R and OX2R receptors, and its loss causes narcolepsy. In a well-designed 2007 study, nasal orexin-A restored cognitive performance in sleep-deprived monkeys better than intravenous dosing. Pharmaceutical development moved to orally available small-molecule OX2R agonists, now in late-stage trials for narcolepsy. The peptide itself has no human cognitive trial and no data on tolerance.
Mechanism of action
Agonism of hypothalamic orexin receptors OX1R and OX2R promoting wakefulness and arousal.
Key studies & citations
- Animal2007
Systemic and nasal delivery of orexin-A reduces the effects of sleep deprivation on cognitive performance in nonhuman primates
Nasal delivery outperformed intravenous in monkeys.
Journal of Neuroscience
Frequently asked questions
Does nasal orexin-A reach the human brain?
Unknown. The monkey data are encouraging, but no human study has measured brain delivery or cognitive effect.