Peptide LibraryOrexin-A
Orexin-A is an endogenous wake-promoting neuropeptide in the Neuromodulator class. Orexin-A is produced by a small population of lateral hypothalamic neurons and binds both orexin receptor 1 and orexin receptor 2, which are Gq-coupled and broadly excitatory. Orexin signalling stabilises wakefulness by exciting monoaminergic and cholinergic arousal nuclei, and also influences feeding, reward and autonomic tone.
For research use only.
Key Facts
- CAS
- 205599-75-3
- Molecular Weight (MW)
- 3561.1 g/mol
- Half-life
- —
- FDA status
- Not Approved
- Evidence level
- Limited Human Evidence
- Human dose established
- No
- Administration Route
- Not established in humans
- Frequency
- Not established in humans
- Last updated
- Nov 7, 2026
- Reviewed
- Nov 7, 2026
Research summary
Endogenous 33-amino-acid hypothalamic neuropeptide central to arousal and wakefulness. Loss of orexin-producing neurons causes narcolepsy type 1. Studied as an intranasal research compound; not FDA-approved.
Research evidence
- Regulatory review (FDA label)None in reviewed sources
- Controlled human trials4 reviewed sources
- Early or uncontrolled human studiesNone in reviewed sources
- Lab & animal studiesNone in reviewed sources
How it works
Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.
Peptide Library's Orexin-A profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Orexin-A dosage: no established human dose
Orexin-A has no established human dosage, but unlike most research peptides it has been given to people in small academic studies. Three published crossover studies sprayed it into the nose as a single amount, 435 nanomoles in two narcolepsy studies and 500 nanomoles in ten healthy men. These were pilot studies of one dose each, with no dose-finding and no approved product, and a later imaging study found little of it reaches the brain by this route.
No established human dosage.
Human clinical evidence: None identified.
Preclinical research: Orexin-A, also called hypocretin-1, is a neuropeptide the brain makes to support wakefulness; narcolepsy type 1 follows the loss of the neurons that make it. The human work is four small academic crossover studies that each gave one amount into the nose, so there is no dose-finding study, no repeated-dosing study and no approved product. Much of the rest of the literature measures the body's own orexin-A in spinal fluid as a diagnostic marker rather than giving it as a treatment, and the animal work gives it into the brain or nose at weight-based doses that do not convert to a human dose.
Animal dosing is not converted into a human dose anywhere on this page. Where research figures appear below, they are reported as studied, not recommended.
| Human dosing established | No |
|---|---|
| Route | Intranasal (the route used in the published human studies) |
| Evidence level | Limited Human Evidence |
| Last reviewed | 2026-11-07 |
Human research reported
Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Crossover study — intranasal orexin-A before night sleep in narcolepsy with cataplexy (2011)Clinical trial · Double-blind, random-order crossover, placebo-controlled pilot study | Adults with narcolepsy with cataplexy (n=8) | 435 nanomoles of human recombinant hypocretin-1 as a single administration | Intranasal | Single administration before night sleep | — | Less REM sleep in the second half of the night and fewer direct wake-to-REM transitions; no statistically significant effect on night-time wakefulness | Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. Sleep Med. 2011. |
| Crossover study — intranasal orexin-A in the morning in narcolepsy with cataplexy (2014)Clinical trial · Within-subject, random-order crossover, placebo-controlled study | Adults with narcolepsy with cataplexy (n=14) | 435 nanomoles as a single administration | Intranasal | Single administration in the morning | — | Fewer wake-to-REM transitions and shorter REM sleep, longer N2 sleep the following night, and fewer false reactions on a divided-attention test | The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Behav Brain Res. 2014. |
| Crossover pilot study — intranasal orexin-A in healthy men (2022)Clinical trial · Balanced, double-blind crossover study | Lean healthy men, mean age 25.8 years (n=10) | 500 nanomoles as a single administration | Intranasal | Single administration | — | Higher resting muscle sympathetic nerve activity 30 to 45 minutes afterwards, with no change in blood pressure, heart rate or baroreflex sensitivity | Intranasal orexin A modulates sympathetic vascular tone: a pilot study in healthy male humans. J Neurophysiol. 2022. |
| Crossover study — intranasal orexin-A and smell in narcolepsy (2008)Clinical trial · Double-blind, randomised, placebo-controlled crossover study | Patients with narcolepsy with cataplexy (n=7 of the 10 studied) | Not stated in the indexed abstract | Intranasal | — | — | Odour detection threshold scores improved in every patient compared with placebo | Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1). Brain. 2008. |
Where sources disagree
- A positron emission tomography study in rodents and monkeys found that little orexin-A reaches the brain after intranasal administration, with uptake similar to intravenous administration except in the olfactory bulbs. That questions how the effects seen in the human studies come about (PMID 29035509).
- A 2024 systematic review of treating narcolepsy type 1 with orexin concluded that it reduced wake-to-REM transitions but did not relieve daytime sleepiness, so orexin deficiency is not the only factor in the disorder (PMID 39898129).
- Most trials registered under "orexin" test orexin receptor blockers such as suvorexant and daridorexant, which are approved insomnia medicines with the opposite action. They are not studies of orexin-A and carry no dosing information for it.
- Doses in these studies are stated in nanomoles of peptide, not in milligrams or micrograms, and were sprayed into the nose by researchers under supervision.
Sequence & molecular data
| Molecular formula | C152H243N47O44S4 |
|---|---|
| Molecular weight | 3561.1 g/mol |
| CAS number | 205599-75-3 |
| PubChem CID | 56842143 |
| FDA UNII | 8RDY08V4VC |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
Orexin-A is produced by a small population of lateral hypothalamic neurons and binds both orexin receptor 1 and orexin receptor 2, which are Gq-coupled and broadly excitatory. Orexin signalling stabilises wakefulness by exciting monoaminergic and cholinergic arousal nuclei, and also influences feeding, reward and autonomic tone. Its size and charge limit brain penetration after peripheral administration, which is why intranasal delivery is the route studied.
Studies
- Treatment of Narcolepsy Type 1 With Orexin: A Systematic Review
- Increased CSF hypocretin-1 (orexin-A) in restless legs syndrome
- Hypocretin-1/ Orexin-A fragment1-16 as a potential surrogate marker for diagnosing narcolepsy type 1
- 16-mer hypocretin-1/orexin-A in cerebrospinal fluid to diagnose narcolepsy
- Detection of reduced orexin-A/hypocretin-1 and its fragments by orexin-A "gold-standard" radioimmunoassay
Research statistics
2,769 PubMed publications · 15.3% human clinical research · 0 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research status
Orexin-A is not an FDA-approved product. It is sold for laboratory research and has no approved medical use.
| FDA status | Not Approved |
|---|---|
| Research status | Research-only compound; no approval pathway listed |
| Availability | Research-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | Research-Only |
How FDA approval, compounding and research-only status differ
Benefits
—
Orexin-A side effects
No side effects listed yet for this entry.
Storage & stability
This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.
Orexin-A: frequently asked questions
What is Orexin-A?
Endogenous 33-amino-acid hypothalamic neuropeptide central to arousal and wakefulness. Loss of orexin-producing neurons causes narcolepsy type 1. Studied as an intranasal research compound; not FDA-approved.
How does Orexin-A work?
Orexin-A is produced by a small population of lateral hypothalamic neurons and binds both orexin receptor 1 and orexin receptor 2, which are Gq-coupled and broadly excitatory. Orexin signalling stabilises wakefulness by exciting monoaminergic and cholinergic arousal nuclei, and also influences feeding, reward and autonomic tone.
Is Orexin-A FDA approved?
No. Orexin-A is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use.
What peptides are similar to Orexin-A?
Compounds most often compared with Orexin-A include Delta Sleep-Inducing Peptide (DSIP), Epitalon, N-Acetyl Selank Amidate and Noopept. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- Treatment of Narcolepsy Type 1 With Orexin: A Systematic Review — Cureus, 2024External reference
- Increased CSF hypocretin-1 (orexin-A) in restless legs syndrome — Neurology, 2002External reference
- Hypocretin-1/ Orexin-A fragment1-16 as a potential surrogate marker for diagnosing narcolepsy type 1 — Sleep, 2026External reference
- 16-mer hypocretin-1/orexin-A in cerebrospinal fluid to diagnose narcolepsy — Sleep, 2025External reference
- Detection of reduced orexin-A/hypocretin-1 and its fragments by orexin-A "gold-standard" radioimmunoassay — Sleep Med, 2025External reference
Related research, comparisons & guides
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2
This Orexin-A profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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