Also known as: Hypocretin-2, OX-B
Half-life: ~30 minutes
Last reviewed: · Published:
Orexin-B (Hypocretin-2) is the sister peptide of Orexin-A, both produced by the same population of hypothalamic neurons by cleavage of the prepro-orexin precursor. Orexin-B is 28 amino acids long and is somewhat more selective for the OX2R receptor than Orexin-A (which binds both OX1R and OX2R with similar affinity). Genetic and pharmacological evidence indicates that OX2R signaling is more directly responsible for the wake-stabilizing function of the orexin system: mice lacking OX2R show narcolepsy-like phenotypes while OX1R knockouts show milder effects, and narcoleptic Dobermans were found to carry a mutation in their OX2R gene.
Because of OX2R's primary role in wakefulness, selective OX2R agonists are being developed as potential treatments for narcolepsy itself (rather than the orexin-receptor antagonists, which are used in the reverse direction for insomnia). Native Orexin-B is one of several peptides used in basic research on this pathway, though synthetic small-molecule OX2R agonists with better pharmacology are more often used in modern preclinical work.
Research-grade Orexin-B is sold by peptide vendors for use in animal experimentation. It has not been clinically tested in humans to a meaningful extent and is not an established research tool for human self-experimentation. Its shorter half-life and greater OX2R selectivity make it of more theoretical than practical interest compared to Orexin-A for typical applications.
Orexin-B was discovered alongside Orexin-A in 1998 by the same two groups (Yanagisawa's at UT Southwestern; de Lecea's at Scripps). The receptor-subtype selectivity of the orexins and the differential role of OX1R vs. OX2R were established through the late 1990s and early 2000s, with the OX2R-narcolepsy link in Dobermans (the Mignot lab at Stanford) being a particularly important finding. Modern orexin-receptor agonist drug development has largely moved to small-molecule compounds rather than the parent peptides.
Human safety data for Orexin-B specifically is essentially absent. By analogy with the broader orexin system and with selective OX2R agonist development, single doses are likely well-tolerated with the intended wake-promoting effect dominating. Chronic safety is unstudied.
Dose Range
Variable per protocol
Frequency
ICV or IV
Duration
Per protocol
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
5 mg
Water Type
Bacteriostatic water (BAC water)
Mixing Volume
2 mL
Half-Life
~30 minutes
Molecular Weight
2,937 Da
Store reconstituted vial refrigerated at 2-8°C. Use within 14 days. Most research use is animal-model only.
FDA Status
Not FDA approved.
Legal Status
Unregulated research chemical.
USA
Not approvedResearch-only
EU
Not approvedNot authorized as medicinal product
UK
Not approvedClassified as research chemical
Australia
Not approvedTGA has not authorized
Canada
Not approvedNot authorized for human use
Sakurai T, Amemiya A, Ishii M, et al.
Cell (1998)
Original discovery paper characterizing both Orexin-A and Orexin-B, establishing the existence of two distinct neuropeptides from the same prepro-orexin precursor.
View Study →Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E
Cell (1999)
Landmark identification of OX2R loss-of-function as the genetic cause of canine narcolepsy, establishing OX2R as the primary receptor subtype mediating wake-stabilization and the principal target for Orexin-B.
View Study →Mieda M, Hasegawa E, Kisanuki YY, Sinton CM, Yanagisawa M, Sakurai T
Journal of Neuroscience (2011)
Detailed genetic dissection of the differential roles of OX1R and OX2R in sleep/wake regulation, establishing OX2R (Orexin-B's preferred target) as the principal wake-stabilizing receptor.
View Study →Track Orexin-B and more with PinnyPeptide.
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