OnePin Peptide Library · Cognitive & Mood
Orexin B
Hypocretin-2 · OX-B
Orexin B (Hypocretin-2) is the second of two endogenous orexin peptides produced by lateral hypothalamic neurons. It is a 28-amino-acid peptide with OX2R-selective binding (vs Orexin A which binds OX1R and OX2R equally). The OX2R selectivity makes Orexin B more focused on the histaminergic wake-promotion pathway (tuberomammillary nucleus) and less involved in OX1R-mediated reward/arousal pathways.
Intranasal route. Refrigerate. Disulfide-containing peptide.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
Orexin B binds primarily to OX2R with ~10x greater affinity than for OX1R, distinguishing it from Orexin A's dual-receptor binding profile:
OX2R-Selective Wake Promotion
OX2R is the dominant orexin receptor on histaminergic tuberomammillary nucleus (TMN) neurons that drive wakefulness. Selective OX2R agonism is the most-targeted pathway for narcolepsy therapy.
Reduced OX1R Effects
Lower OX1R activation means less effect on dopaminergic VTA reward pathways and locus coeruleus arousal compared to Orexin A. This may reduce cardiovascular and reward-related side effects.
Same Therapeutic Application
Like Orexin A, candidate narcolepsy replacement therapy. The OX2R selectivity may give Orexin B a cleaner clinical profile in principle.
Disulfide-Containing
Like Orexin A, contains intramolecular disulfide bonds - chemistry-incompatible with copper-conjugated peptides.
Same BBB Challenge
Intact peptide poorly crosses BBB. Intranasal route bypasses this for clinical research.
What to expect
Acute wakefulness within 15-30 min intranasal.
Effects fade with plasma clearance.
No long-term effects characterized.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Keep separate
Side effects & safety
Commonly reported
- Nasal irritation (intranasal)
- Mild stimulation
Less common & notes
- Cleaner side-effect profile theoretically vs Orexin A due to OX2R selectivity.
- Long-term safety not characterized.
Pharmacokinetics
Storage. Refrigerate. Light-sensitive. Disulfide-containing - keep cold.
Regulatory status
Not FDA-approved. Research chemical only.
Put it to work
Calculate, log & track
Open Orexin B straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
Open Orexin B in the app →Go deeper
The guide & community
The complete Orexin B walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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