Orexin A (Hypocretin-1) 5mg

Orexin A, also called hypocretin-1, is a 33-residue neuropeptide made by a few thousand neurons in the lateral hypothalamus. Two groups described it independently in 1998; within two years its absence had been identified as the lesion behind human narcolepsy type 1. It carries an N-terminal pyroglutamate, a C-terminal amide and two intrachain disulfide bonds. This listing is the 5 mg vial of freeze-dried powder, the only fill. The mature sequence is identical in humans, rats, mice, dogs, pigs and cattle, so there is no species version to choose.

Specifications

What the structure is

pGlu-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, with disulfides Cys6-Cys12 and Cys7-Cys14. Formula C₁₅₂H₂₄₃N₄₇O₄₄S₄, theoretical mass 3561.1 Da (PubChem CID 56842143, CAS 205599-75-3, UniProt O43612 residues 34-66). No methionine or tryptophan; the single tyrosine allows quantification at 280 nm. Its octanol/buffer partition coefficient of 0.23 is high for a peptide and is the reason it crosses the mouse blood-brain barrier by diffusion when orexin B does not.

A reduced, mis-paired, free-acid or non-pyroglutamyl preparation is a different analytical entity sold under the same name, so the certificate’s mass and the absence of free thiols are what confirm the native form. Reducing agents such as DTT or TCEP open the disulfides.

What the research covers

Discovery and receptor pharmacology

Orexin-A and orexin-B were identified in 1998 as two peptides processed from one hypothalamic precursor that bind and activate two closely related G protein-coupled receptors, now OX1 and OX2¹. The same peptides were reported independently as the hypocretins, confined to neurons of the dorsal and lateral hypothalamus with projections to brainstem and thalamus, one of which excited cultured hypothalamic but not hippocampal neurons². In CHO cells expressing the human receptors, orexin-A activates OX1 and OX2 with comparable affinity and potency while orexin-B is 10- to 100-fold weaker at OX1; stepwise truncation reduced activity at both subtypes, and alanine replacement identified Leu20, Asp25 and His26 as particularly important residues⁶.

Arousal and sleep-wake regulation

In rats, the brain region most densely innervated by orexin fibres is the locus coeruleus; local application of orexin A increased firing of its noradrenergic neurones, and central orexin A increased arousal and locomotor activity³. Mice lacking the prepro-orexin gene show a phenotype strikingly similar to human narcolepsy by behavioural and EEG criteria⁴. In humans, cerebrospinal fluid hypocretin-1 was undetectable in seven of nine patients with narcolepsy, which established orexin-A deficiency as the lesion in narcolepsy type 1⁵. These findings are what make orexin-A a wake-promoting peptide of interest rather than only a feeding peptide.

Feeding

The peptide was named for its orexigenic action: centrally administered orexin-A increased food consumption in rats, and prepro-orexin mRNA was up-regulated by fasting, which the original authors read as a role in central feedback control of feeding¹. This effect has been characterised almost entirely by central (intracerebroventricular or intrahypothalamic) administration in rodents; it is one of several orexigenic signals rather than a dominant one.

Blood-brain barrier behaviour and intranasal administration

In mice, an intravenous bolus of radiolabelled orexin A entered the brain rapidly by a non-saturable route consistent with simple diffusion, reached brain parenchyma largely as intact peptide, and had an octanol/buffer partition coefficient of 0.232; orexin B, by contrast, was degraded in blood and could not be detected intact in brain⁷. In a placebo-controlled crossover study in 14 patients with narcolepsy with cataplexy, intranasal orexin-A (435 nmol, given in the morning) reduced wake-to-REM transitions and REM sleep duration and produced fewer false reactions on a divided-attention test⁸; this is the only controlled human administration study of the peptide located.

What is not established

The arousal and narcolepsy findings are replicated across species and laboratories, but evidence for exogenous orexin-A as an intervention is thin: the human work is confined to small pilot crossover studies in narcolepsy using intranasal peptide, with surrogate endpoints (REM-sleep measures, attention tasks) and no large or long-term trial⁸; clinical development for narcolepsy has instead moved to small-molecule OX2 receptor agonists. The feeding effect is documented by central administration in rodents¹, and its relevance after any peripheral route is unclear. Blood-brain barrier entry by diffusion has been shown in mice⁷; it has not been characterised comparably in other species, and the pharmacokinetics of intranasal delivery in humans are not well defined. None of the cited work used this supplier’s material.

Clinical and regulatory status

Orexin-A is not an approved drug anywhere and has been used only as an investigational peptide in a small academic crossover study⁸. The pathway it acts on is nonetheless a validated drug target: dual orexin receptor antagonists are approved insomnia drugs, and on 5 August 2026 the US FDA approved oveporexton (Orzeyful, Takeda), an oral small-molecule OX2 receptor agonist, for narcolepsy type 1 in adults on the basis of the phase 3 FirstLight and RadiantLight trials. The lyophilized peptide listed here is a research-grade material, not a pharmaceutical product.

Related listings: Orexin B (Hypocretin-2) 5mg, DSIP 10MG, Selank 11mg, Semax 11mg, Pinealon 10mg. The cognitive, sleep and mood peptides category lists the rest of the range.

How each lot is tested

Every lot is tested in PrymaLab’s own laboratory in Ashland, Kentucky before release: RP-HPLC for purity, LC-MS for identity, Karl Fischer titration for water, LAL for endotoxin and USP <71> for sterility. Published certificates are listed on the results page and can be checked by number and key on the verify page. These are in-house results from PrymaLab Analytical, not an independent test, and the lab is not accredited to ISO 17025. The third-party testing guarantee on this page still applies: if any independent laboratory finds the wrong compound, or less than the stated purity or amount, the order is refunded and the cost of the test is reimbursed.

Frequently asked questions

References

1. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573-85. DOI · PubMed
2. de Lecea L, Kilduff TS, Peyron C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322-7. DOI · PubMed
3. Hagan JJ, Leslie RA, Patel S, et al. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci U S A. 1999;96(19):10911-6. DOI · PubMed
4. Chemelli RM, Willie JT, Sinton CM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999;98(4):437-51. DOI · PubMed
5. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000;355(9197):39-40. DOI · PubMed
6. Ammoun S, Holmqvist T, Shariatmadari R, et al. Distinct recognition of OX1 and OX2 receptors by orexin peptides. J Pharmacol Exp Ther. 2003;305(2):507-14. DOI · PubMed
7. Kastin AJ, Akerstrom V. Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther. 1999;289(1):219-23. DOI · PubMed
8. Weinhold SL, Seeck-Hirschner M, Nowak A, Hallschmid M, Göder R, Baier PC. The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Behav Brain Res. 2014;262:8-13. DOI · PubMed