OREXIN A - 5mg

SPECIFICATIONS

Product Code: ORE005

Sequence: Glp-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu-NH₂

Disulfide Bridges: 6–12; 7–14

Molecular Formula: C152H243N47O44S4

Molecular Weight: 3561.1 g/mol

CAS: 205599-75-3

Purity: Technical / Research Grade ≥98%

Other details: No TFA Salt

Form: Lyophilized powder

Color: White

Storage temperature: -20°C

Source: Synthetic

Safety classification: Standard handling

DESCRIPTION

Orexin neuropeptides were independently identified in 1998 by two research groups. Sakurai and Yanagisawa named them orexin-A and orexin-B due to their initially proposed role in appetite regulation (orexis = appetite). In parallel, de Lecea and Sutcliffe referred to them as hypocretin-1 and hypocretin-2, reflecting their hypothalamic origin and structural similarity to incretin peptides.

Subsequent research demonstrated that orexins exert modest effects on feeding but play a central role in arousal and sleep regulation. Narcolepsy has been strongly associated with the loss of orexin-producing neurons, leading to significant interest in orexin receptor modulation in sleep research.

Orexin-A and orexin-B are produced by neurons in the lateral hypothalamus and regulate wakefulness and arousal. They stimulate brain regions including the raphe nuclei, ventral tegmental area, tuberomammillary nucleus, and locus coeruleus, promoting neurotransmitter release such as dopamine, norepinephrine, serotonin, and histamine. This coordinated activation stabilizes sleep–wake transitions and prevents inappropriate REM intrusion.

Approximately 90% of individuals with narcolepsy and cataplexy exhibit low or undetectable orexin levels in cerebrospinal fluid, reflecting significant loss of orexinergic neurons.

Orexin receptor antagonism has been explored as a mechanism to promote sleep in insomnia research. Orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) are G protein-coupled receptors central to sleep–wake homeostasis.

Animal studies confirm that activation of orexin pathways increases arousal, whereas inhibition promotes sleep. Orexinergic neurons are functionally opposed by inhibitory GABAergic neurons from the ventrolateral preoptic nucleus (VLPO), demonstrating a balanced interplay between arousal and sleep systems.

Orexins also contribute to thermoregulation. Animal models lacking orexin neurons display reduced hyperthermic responses to cold exposure, suggesting involvement in metabolic and thermogenic homeostasis.

Hypocretin-1 levels in lumbar CSF have been studied in chronic migraine and medication-overuse headache, where elevated concentrations have been observed. Migraine prevalence is increased in narcoleptic populations, suggesting potential involvement of hypocretin signaling in headache pathophysiology.

Orexin-A (OXA) and orexin-B (OXB) influence feeding, sleep–wake cycles, metabolism, neuroendocrine signaling, and immune responses. OXA binds both OXR1 and OXR2 with similar affinity, whereas OXB preferentially binds OXR2.

Research indicates that OXA can cross the blood–brain barrier via passive diffusion, whereas OXB does not exhibit the same property. Receptor distribution is region-specific, with OXR1 predominant in the dorsal raphe and hippocampal regions, and OXR2 primarily expressed in basal ganglia structures.

Experimental models suggest neuroprotective properties of OXA in cerebral ischemia. Studies report reduced expression of pro-inflammatory cytokines such as TNF-α and IL-6 following administration.

In hemorrhagic stroke models, secondary brain injury (SBI) involves inflammation, oxidative stress, and neuronal apoptosis. Research proposes that OXA may mitigate neuroinflammatory responses associated with SBI.

Orexins also regulate autonomic and metabolic processes. They increase sympathetic tone, blood pressure, heart rate, and circulating norepinephrine. Animal models deficient in orexin signaling exhibit reduced energy expenditure, decreased locomotor activity, mild obesity, and lower blood pressure. Similar metabolic tendencies have been observed in narcoleptic individuals.

REFERENCES

All observations described above originate from in vitro systems, animal studies, or other preclinical experimental models. They are intended solely to support basic research into molecular, cellular, and physiological mechanisms and do not imply therapeutic, diagnostic, or preventive applications in humans or animals.

C. B. Calva et al., “Effects of Intranasal Orexin-A (Hypocretin-1) Administration on Neuronal Activation, Neurochemistry, and Attention in Aged Rats” [Frontiers in Aging Neuroscience]

Tao Li et al., “Orexin A alleviates neuroinflammation via OXR2/CaMKKβ/AMPK signaling pathway after ICH in mice” [BMC]

T. E. Scammell et al., “Orexin Receptors: Pharmacology and Therapeutic Opportunities” [PMC]

M. Lang et al., “Structure–Activity Studies of Orexin A and Orexin B at Human Orexin Receptors” [Journal of Medicinal Chemistry]

A. Yamanaka et al., “Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor” [The Journal of Neuroscience]

J. P. Nixon et al., “Comparative distribution of orexin A and B in nocturnal and diurnal rodents” [BMC]

S. Goodrick, “Orexin or hypocretin?” [The Lancet]

M. Mieda et al., “Orexin peptides prevent cataplexy and improve wakefulness in narcolepsy models” [PNAS]

K. Bieganska et al., “Orexin A suppresses growth of rat C6 glioma cells” [Journal of Molecular Neuroscience]

J. E. Digby et al., “Orexin receptor expression in human adipose tissue” [Journal of Endocrinology]

K. Hirota et al., “Orexin A and B evoke noradrenaline release” [British Journal of Pharmacology]

DISCLAIMER

This product is intended for laboratory research and development use only. These studies are performed outside of the body. This product is not a medicine or drug and has not been approved by the FDA or EMA to prevent, treat, or cure any medical condition, ailment, or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals.

All product information provided on this website is for informational and educational purposes only.