An endogenous hypothalamic neuropeptide that promotes wakefulness, arousal, and appetite, with profound relevance to narcolepsy, sleep disorders, and cognitive enhancement research.
Half-Life
~20 minutes (CSF); ~4-5 minutes (plasma, rapid enzymatic degradation)
MW
3561.9 Da
Amino Acids
33 AA
Evidence
High Evidence
Regulatory Status
Endogenous neuropeptide. Not commercially available as a therapeutic peptide. Studied extensively in animal models and human intranasal trials. Dual orexin receptor antagonists (suvorexant, lemborexant) are FDA-approved as insomnia treatments via orexin blockade — confirming therapeutic relevance of this system.
In Plain English
The brain's own "stay awake" signal. Orexin-A is produced by a tiny cluster of neurons that acts as the master switch for wakefulness — when these neurons die (in narcolepsy), people randomly fall asleep. Researchers use intranasal orexin-A to restore alertness after sleep deprivation and explore treatments for narcolepsy and Alzheimer's. Sleep drug developers do the opposite: blocking orexin (like Ambien's successor, suvorexant).
Overview
Orexin-A (also called Hypocretin-1) is a 33-amino acid neuropeptide produced exclusively by ~10,000–80,000 neurons in the lateral hypothalamus and perifornical area. Together with Orexin-B (28 AA), it regulates wakefulness, arousal, energy homeostasis, reward processing, and appetite. Loss of orexin-producing neurons causes narcolepsy type 1 (with cataplexy) — demonstrating the peptide's essential role in maintaining wakefulness. Orexin-A signals via two receptors: OX1R (orexin receptor 1) and OX2R. OX1R is more selective for Orexin-A; OX2R is activated by both orexins with higher affinity for Orexin-B. In the research community, intranasal orexin-A administration has been studied for cognitive enhancement in sleep-deprived subjects, PTSD, and as a potential therapy for narcolepsy, hypersomnia, and Alzheimer's disease.
Common Formats
- Research-grade lyophilized powder (intranasal or ICV research)
- Not commercially available for human therapeutic use
Storage Notes
Lyophilized: -20°C long-term, 4°C short-term. Reconstituted solution: stable 1-2 weeks at 4°C, pH 4-7. Avoid repeated freeze-thaw.
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Related Compounds
DSIP
A naturally occurring neuropeptide that regulates sleep-wake cycles, stress response, and has shown longevity-associated effects in animal research.
Semax
A synthetic heptapeptide based on ACTH fragment with potent nootropic, neuroprotective, and stroke-recovery properties developed in Russia.
Selank
A synthetic heptapeptide analogue of tuftsin with anxiolytic, nootropic, and immune-modulating properties developed in Russia.
VIP (Vasoactive Intestinal Peptide)
A 28-amino acid neuropeptide and potent immunomodulator with anti-inflammatory, vasodilatory, and neuroprotective properties, with an extensive clinical research history in autoimmune, inflammatory, and pulmonary conditions.
Educational Disclaimer: All information on this page is for educational and research purposes only. This does not constitute medical advice, diagnosis, or treatment recommendation. Consult a qualified healthcare professional.