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Brain & Cognitive

Orexin B

Hypocretin-2

The wakefulness signal's sibling.

Half-life

~ short

Mol. weight

2918.4 g/mol (approx, linear)

Sequence

28-amino-acid neuropeptide (linear, no disulfide bonds)

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Overview

The second of the two orexin/hypocretin neuropeptides, sharing the same hypothalamic origin and wakefulness-regulating role as Orexin A but with distinct receptor selectivity — preferentially activating the orexin-2 (OX2R) receptor. It is studied alongside Orexin A to dissect how the two peptides divide the arousal-control workload.

Mechanism of action

Orexin B is derived from the same prepro-orexin precursor as Orexin A and signals through the same family of receptors, but with a preference for the orexin-2 (OX2R) receptor (whereas Orexin A is relatively non-selective). The OX2R pathway is particularly implicated in sleep-wake stabilization and narcolepsy pathophysiology. Studying the two peptides together lets researchers separate the arousal components each receptor mediates.

Researched benefits

  • Co-regulates wakefulness alongside Orexin A
  • OX2R-selective — linked to sleep-wake stabilization
  • Useful for dissecting orexin receptor subtypes

Considerations

  • Short half-life; poor blood-brain barrier penetration
  • Not approved for human use
  • Cardiovascular and arousal considerations

Key Academic Literature & Studies

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Peer-reviewed citations and clinical trials evaluating Orexin B in scientific literature.

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View Orexin B index on PubMed (NCBI)

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