Sleep, Mood & Stress; Metabolic & Weight Management

Orexin-A

Orexin-A is the hypothalamic signal that holds wakefulness together, and its importance was established by subtraction: people with narcolepsy type 1 have lost the neurons that make it, which is about as clean a demonstration as human biology offers of what one peptide is for. What has been done with it in people is small — single intranasal doses in healthy men and in narcolepsy patients, plus an observational memory-clinic cohort relating spinal-fluid orexin to sleep rhythms in Alzheimer's disease. It also drives eating: a single dose into a rat's brain increases food intake, so a compound filed under sleep is an appetite stimulant in every direct measurement the corpus holds.

Last updated 12 August 2026

Studied forWakefulness research · Narcolepsy research · Appetite and motivation context

Evidence on file1 human observational study · 4 animal studies

Strongest sourceOrexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. (human observational study)

Mechanism

Binds both OX1 and OX2 G-protein-coupled receptors, exciting locus coeruleus and tuberomammillary arousal circuits and stabilising wakefulness.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

Wakefulness research
Narcolepsy research
Appetite and motivation context

Dosing on file unverified

435-500 nmol intranasal single dose; 1.0 µg/kg in some studies; 500 nmol (~2.2 mg) or 435 nmol (~1.9 mg) intranasal (research)

Carried from a source that labels it unverified, and reproduced with that label attached. A record of what is reported, not a recommendation. No citation on this page establishes it.

Literature on file 6

animal in vivo
Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor (2010, cited 100x) graded on: an animal model — read from the indexed abstract — “mice”
review or editorial
Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders. graded on: indexed as "Review" - secondary literature, not a study — “Review”
animal in vivo
Involvement of the cannabinoid receptors of the basolateral amygdala in the orexin A-mediated modulation of the stress-induced analgesia. graded on: an animal model — read from the indexed abstract — “rats”
animal in vivo
Small molecule orexin agonist ROXA-47 enhances learning and memory in mice. graded on: an animal model — “mice”
human observational
Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience. graded on: an observational human design — the indexed publication type — “Observational”
animal in vivo
The Orexin System Modulates Stress-Induced Alcohol Preference and Reinstatement in Adolescents: Bioinformatics and Experimental Evidence. graded on: an animal model — read from the indexed abstract — “mice”

Identity

Space-filling 3D model of Orexin-A, carbon grey, nitrogen blue, oxygen red — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

2D chemical structure of Orexin-A — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

Molecular weight: 3561.1
Molecular formula: C152H243N47O44S4
CAS number: 205599-75-3
PubChem CID: 56842143
UniProt: O43612 (precursor)
InChI key: OFNHNCAUVYOTPM-IIIOAANCSA-N
SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)N)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]4CSSC[C@H]5C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N5)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]6CCCN6C(=O)[C@H](CC(C)C)NC(=O)[C@@H]7CCCN7C(=O)[C@@H]8CCC(=O)N8)C(=O)N[C@H](C(=O)N4)CO)[C@@H](C)O)CCCCN)CCC(=O)N)CCCNC(=N)N
InChI: InChI=1S/C152H243N47O44S4/c1-20-76(14)118(146(239)188-96(51-74(10)11)138(231)197-119(80(18)201)147(240)180-92(121(156)214)47-70(2)3)195-115(209)62-166-123(216)78(16)171-124(217)79(17)172-131(224)99(55-84-59-162-69-169-84)186-136(229)100(56-111(155)205)174-114(208)61-165-122(215)77(15)170-113(207)60-167-125(218)98(54-83-58-161-68-168-83)185-134(227)95(50-73(8)9)183-132(225)93(48-71(4)5)182-129(222)90(38-41-116(210)211)179-135(228)97(53-82-32-34-85(203)35-33-82)184-133(226)94(49-72(6)7)181-127(220)88(29-24-44-164-152(159)160)177-140(233)104-64-244-245-65-105-141(234)176-87(28-23-43-163-151(157)158)126(219)178-89(36-39-110(154)204)128(221)175-86(27-21-22-42-153)130(223)196-120(81(19)202)148(241)194-107(142(235)190-103(63-200)139(232)192-104)67-247-246-66-106(143(236)193-105)191-137(230)101(57-117(212)213)187-144(237)108-30-26-46-199(108)150(243)102(52-75(12)13)189-145(238)109-31-25-45-198(109)149(242)91-37-40-112(206)173-91/h32-35,58-59,68-81,86-109,118-120,200-203H,20-31,36-57,60-67,153H2,1-19H3,(H2,154,204)(H2,155,205)(H2,156,214)(H,161,168)(H,162,169)(H,165,215)(H,166,216)(H,167,218)(H,170,207)(H,171,217)(H,172,224)(H,173,206)(H,174,208)(H,175,221)(H,176,234)(H,177,233)(H,178,219)(H,179,228)(H,180,240)(H,181,220)(H,182,222)(H,183,225)(H,184,226)(H,185,227)(H,186,229)(H,187,237)(H,188,239)(H,189,238)(H,190,235)(H,191,230)(H,192,232)(H,193,236)(H,194,241)(H,195,209)(H,196,223)(H,197,231)(H,210,211)(H,212,213)(H4,157,158,163)(H4,159,160,164)/t76-,77-,78-,79-,80+,81+,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,118-,119-,120-/m0/s1

Also called

Orexin-A (Wakefulness)

Caveat on these identifiers

Source files disagreed on evidence tier for this peptide.

Notes unverified prose

Human studies: 500 nmol in healthy males; 435 nmol in narcolepsy with cataplexy; 500 nmol intranasal in healthy males; Human intranasal studies

Not on file 2

1 of the 8 fields we track hold nothing on this record, and each says why. 1 further absence is named below. A blank field is a bug; a named absence is a finding.

amino-acid sequencenothing we hold supplies it
half-lifenothing we hold supplies it

Each field links to every other record missing the same thing. The full ledger holds 765 gaps across 163 records.

Listed prices 10

What 7 shops we track listed for Orexin-A, read from their own public catalogues on 2026-09-14. We take no commission on these and they are not ranked by any payment — how vendors are scored.

Compare prices10 listings from 7 shops

Listed in GBP
Vendor	Size	Price	Per mg
Direct Peptides Canada	5 mg	£98.75 GBP	£19.75/mg
Direct Peptides USA	5 mg	£98.75 GBP	£19.75/mg
Pharma Lab Global Canada	5 mg	£99.28 GBP	£19.86/mg
Direct Peptides Canada	5 mg	£107.73 GBP	£21.55/mg
Direct Peptides USA	5 mg	£107.73 GBP	£21.55/mg
Pharma Lab Global Canada	5 mg	£108.26 GBP	£21.65/mg

Listed in USD
Vendor	Size	Price	Per mg
PureRawz ships worldwide	5 mg	$95.62 USD	$19.12/mg
Behemoth Labz	5 mg	$96.63 USD	$19.33/mg
Nootropic Source	size not listed	$89.95 USD	—
Peptide Works	size not listed	$119.16 USD	—

Prices are the vendor's own listing, reproduced with the date we read it — never converted between currencies, and compared per milligram only where the vendor states the vial size.

At a glance

Strongest rung: human observational
Citations: 6
Regulatory: Human research reported (unverified)
Route: Intranasal
Declared gaps: 2

Citations by rung

Strongest wins, never an average.