Description
Orexin B (also hypocretin-2) is a 28-amino-acid neuropeptide produced in the mammalian brain exclusively by a small cluster of neurons in the lateral and posterior hypothalamus. Orexin A and orexin B both arise from the same precursor protein, prepro-orexin, and were described in 1998 by the Sakurai group as the endogenous ligands of two G-protein-coupled receptors. Both peptides therefore belong to the class of hypothalamic neuropeptides. The name derives from the Greek “orexis” (appetite), reflecting the originally discovered role in the control of food intake.
The central difference from orexin A lies in receptor selectivity: while orexin A activates both the OX1R and the OX2R with similar potency, orexin B in the research context binds preferentially to the OX2R. Phylogenetic work suggests that orexin B is the evolutionarily older form of the peptide and that the OX2R is the prototype receptor of the system. The OX2R is expressed particularly strongly in wake-promoting nuclei, including the histaminergic neurons of the tuberomammillary nucleus. It is precisely along this axis that studies link orexin to arousal.
Pharmacokinetically, orexin B is a classic centrally acting peptide. In the research literature it is administered almost exclusively intracerebroventricularly (ICV), meaning directly into the brain’s ventricular system, because peptides of this size cross the blood-brain barrier only to a limited extent and are rapidly broken down by enzymes in the blood. No robust human data on half-life or systemic bioavailability exist. The known findings derive predominantly from animal models and in-vitro electrophysiology.
Central research findings revolve around wakefulness and arousal: ICV administration of OX2R-selective orexin-B variants dose-dependently increased wake duration in rodents and shifted the sleep-wake ratio. Conversely, loss of the orexin system produces a narcolepsy-like phenotype in knockout models, underscoring the system’s key role in the stability of the waking state within the research context. Alongside this, the appetite-stimulating component that gave the peptide its name is documented. Orexin B is thus purely a tool of neuroscience research and not an application substance.
You receive orexin B as a research substance in 10-packs with 5mg per vial. The size depends on the scope and duration of your research protocol.
This information is for research and educational purposes only. Not medical advice.
Studies
- Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior - Sakurai et al., Cell 1998: First description of orexin A and B, identification of the OX receptors and the appetite-stimulating effect after central administration in rats.
- Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats - Akanmu & Honda, Brain Research 2005: ICV administration of orexin B and the OX2R-selective variant [Ala11]orexin-B dose-dependently increased wake duration and reduced REM and non-REM sleep (animal model).
- Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus - Eriksson et al., Journal of Neuroscience 2001: Orexin A and B depolarized histaminergic neurons and increased their firing rate, primarily via the more strongly expressed OX2R (in-vitro electrophysiology).
- Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation - Chemelli et al., Cell 1999: Orexin knockout mice show a narcolepsy-like phenotype, demonstrating the system’s role in sleep-wake regulation (preclinical).
- Effect of intracerebroventricular orexin-B on food intake in sheep - Sartin et al., Journal of Animal Science 2001: Central ICV administration of orexin B increased feed intake, while intravenous administration had no effect (animal model of the appetite component).
- Hypocretin/Orexin Receptor Pharmacology and Sleep Phases - Sun, Tisdale & Kilduff, Frontiers of Neurology and Neuroscience 2021: Review of receptor pharmacology, linking OX2R primarily to sleep-wake control and OX1R to motivation and reward.
Stack Notes
- Selank - as a nootropic-oriented research peptide, Selank is often examined alongside arousal ligands such as orexin B, because both address different layers of wakefulness and stress modulation.
- Semax - Semax is associated in the research context with cognitive and neurotrophic activity, complementing the purely arousal-focused axis of orexin B with a second investigative dimension.
- Cerebrolysin - as a neurotrophic research preparation, Cerebrolysin covers a pathway distinct from OX2R-mediated wake signaling and is often positioned as a complementary tool in neuro stacks.
- DSIP - DSIP (Delta Sleep-Inducing Peptide) sits mechanistically at the opposite pole of the sleep-wake axis and is therefore a logical counterpart compound when both sides of the cycle are to be represented in a research design.
- Pinealon - the short-chain cytogen Pinealon is assigned in research to the area of neuronal regulation and can be studied as an additional building block alongside the orexin system.
