Research Only Cognitive & Nootropic

Orexin-B

also known as: Hypocretin-2, OX-B, HCRT-2

The second orexin isoform — a 28-amino-acid peptide that preferentially activates the OX2 receptor most critical for maintaining wakefulness.

A 28-amino-acid linear peptide co-produced with Orexin-A from prepro-orexin that selectively activates OX2R and is less stable than Orexin-A due to its lack of disulfide bonds.

Mechanism of action

Binds OX2R with high affinity and OX1R with ~10-fold lower affinity. OX2R is the dominant receptor for wakefulness — OX2R knockout mice exhibit severe narcolepsy while OX1R knockout mice show milder sleep fragmentation.

Primary uses

Endogenous wakefulness maintenance (OX2R-mediated)
Research tool for dissecting OX1R vs OX2R contributions to sleep/wake regulation

Typical dosing

N/A N/A N/A (endogenous)

Not used therapeutically. CSF Orexin-B is not routinely measured clinically.

Regulatory status

Not approved as a drug. Same receptor targets as Orexin-A. OX2R-selective agonists in development may have advantages for narcolepsy treatment.

References

[pubmed] Sakurai T, et al. "Orexins and orexin receptors." Cell. 1998;92(4):573-585.
[review] Mieda M. "The roles of orexins in sleep/wake regulation." Neurosci Res. 2017;118:56-65.

Related peptides

Orexin-A

The hypothalamic wakefulness peptide — loss of orexin neurons causes narcolepsy, and blocking its receptors produced the blockbuster insomnia drugs suvorexant and lemborexant.

Neuropeptide Y

The brain's most abundant neuropeptide — a 36-amino-acid master regulator of appetite, stress resilience, and anxiety that connects metabolic and cognitive peptide networks.

DSIP

An endogenous 9-amino-acid peptide named for its ability to induce delta-wave sleep in early rabbit experiments, with broader effects on stress response, pain modulation, and circadian regulation.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.