Cognitive ⏱ Half-life: ~30 minutes (plasma) Experimental

Orexin-A

Orexin-A (Hypocretin-1)

Updated March 30, 2026

Evidence at a Glance

Regulatory statusExperimental
Small intranasal pilot studies in narcolepsy; not approved. Formal drug development targets small-molecule orexin agonists, not the peptide.
Human evidenceLimited
Animal evidenceModerate

Intranasal orexin-A stabilized REM sleep in small narcolepsy pilot studies but did not reliably improve daytime wakefulness or cataplexy, and it is not an approved therapy.

What the research does not support

  • It is not FDA-approved and is not a proven treatment for narcolepsy, sleepiness, or cognition.
  • Poor brain penetration limited its effects in the few small human studies conducted.
  • It did not reduce cataplexy in the trials that tested it.
  • It is not the same as the small-molecule orexin agonists being developed as actual medicines.
Half-Life
~30 minutes (plasma)
Purity
≥95%
Mol. Weight
3,562 Da
Form
Lyophilized powder

What is Orexin-A?

Orexin-A (also called hypocretin-1) is a 33-amino acid neuropeptide discovered in 1998 that fundamentally changed our understanding of sleep-wake regulation. The discovery that narcolepsy is caused by loss of orexin neurons transformed it from a curiosity into one of the most therapeutically important neuropeptide systems.

Dosage Information (Research Use)

Research: ICV injection in animal models, typically 1-10 nmol. Intranasal delivery under investigation for human use. No approved dosing protocol. Research compound only.

Reconstitution & Handling

Reconstitute in sterile saline or aCSF for research use.

Half-Life & Pharmacokinetics

~30 minutes (plasma)

Reported Observations in Literature

Increased wakefulness and alertness. Potential appetite stimulation. Cardiovascular effects (increased blood pressure and heart rate) at high doses. May affect stress responses through HPA axis activation.

Key Research References

  • Sakurai T et al. “Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors.” Cell. 1998;92:573-85

How Orexin-A Works

Orexin-A acts on orexin receptors OX1R and OX2R, primarily in the hypothalamus and brainstem arousal centers. It promotes wakefulness by exciting wake-active neurons in the locus coeruleus (norepinephrine), tuberomammillary nucleus (histamine), and dorsal raphe (serotonin). The orexin system integrates metabolic status with arousal — when energy reserves are low, orexin neurons fire more, promoting wakefulness and food-seeking behavior.

Research Applications

🔬 Narcolepsy and sleep disorders
🔬 Obesity and metabolic syndrome
🔬 Drug addiction and reward circuits

Research Findings

Narcolepsy type 1 is caused by selective autoimmune destruction of orexin neurons. Suvorexant and lemborexant (orexin receptor antagonists) are FDA-approved insomnia treatments, validating the pathway. Orexin replacement therapy for narcolepsy is under active investigation, including intranasal delivery approaches.

Dosage & Administration

Research: ICV injection in animal models, typically 1-10 nmol. Intranasal delivery under investigation for human use. No approved dosing protocol. Research compound only.

Safety & Side Effects

Increased wakefulness and alertness. Potential appetite stimulation. Cardiovascular effects (increased blood pressure and heart rate) at high doses. May affect stress responses through HPA axis activation.

Important: All safety information is derived from published research, primarily animal studies. No controlled human clinical trial data exists unless explicitly noted. This compound is sold for research purposes only.

Quick Facts

Molecular Weight 3,562 Da
Half-Life ~30 minutes (plasma)
Purity ≥95%
Form Lyophilized powder
Storage Lyophilized: -20°C. Reconstituted: 2-8°C, use within 48 hours.

Key Research References

  • Sakurai T et al. "Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors." Cell. 1998;92:573-85

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