Nocistatin (NST)
An endogenous peptide cut from the same precursor as nociceptin but with opposite effects — it blocks nociceptin-driven pain. A research peptide, not a drug
Nocistatin (NST) is an endogenous brain and spinal-cord peptide with an unusual origin: it is cut from the very same precursor protein (prepronociceptin) that produces nociceptin, also called orphanin FQ — yet the two peptides pull in opposite directions. Where nociceptin injected into the spinal fluid produces touch-evoked pain (allodynia) and heightened pain sensitivity (hyperalgesia), nocistatin blocks both, and it dampens inflammatory pain. Its active part is a short, species-conserved tail (the hexapeptide Glu-Gln-Lys-Gln-Leu-Gln). Beyond pain it suppresses feeding, protects learning and memory from nociceptin’s disrupting effect, and influences smooth-muscle tone. Curiously, nocistatin does not bind the nociceptin receptor, and its own receptor has never been identified — it is thought to act through a separate, still-unknown G-protein-coupled receptor. Nocistatin is studied as a research tool and a lead for pain biology; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Nocistatin is an endogenous human peptide that has never been given to people as a treatment. The human evidence is its presence in brain and cerebrospinal fluid; the functional studies are in animals and cells, where it is injected into the brain or spinal fluid or applied to tissues at experimental amounts that do not carry over to people.
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What is it?
Nocistatin was discovered in the late 1990s by researchers studying the precursor protein that makes nociceptin (orphanin FQ), an endogenous peptide that acts on the opioid-like NOP receptor. That precursor, prepronociceptin, turned out to carry a second bioactive peptide alongside nociceptin — nocistatin — and it was isolated from bovine brain and later found in human, rat and mouse brain and in human cerebrospinal fluid. The human peptide is 30 amino acids long, and its biological punch lives in a short, species-conserved tail: the hexapeptide Glu-Gln-Lys-Gln-Leu-Gln.
The striking thing about nocistatin is that it opposes its own sibling. When nociceptin is injected into the spinal fluid it causes allodynia (pain from a light touch) and hyperalgesia (exaggerated pain); nocistatin, given at the same time, blocks both. It also blunts inflammatory pain driven by prostaglandin E2 or by formalin and carrageenan, and it reverses nociceptin’s ability to undercut morphine’s painkilling effect. Because both peptides come from one precursor, how the body processes that precursor may help set the balance of pain signalling.
Nocistatin’s reach extends past pain. Injected into the brain of rats it suppresses food intake and blocks the overeating that nociceptin provokes, without causing taste aversion. It protects learning and memory against the impairment nociceptin or scopolamine cause. At the cellular level it sensitizes the TRPA1 ‘irritant’ ion channel in sensory neurons, and in isolated rat uterus it inhibits contractions through calcitonin-gene-related peptide and calcium-dependent potassium channels — showing it also touches smooth-muscle tone.
A long-standing puzzle is how nocistatin works. It does not bind the nociceptin (NOP) receptor, yet it binds brain and spinal-cord membranes with high affinity and produces pertussis-toxin-sensitive effects — the fingerprint of a G-protein-coupled receptor. More than a decade of work points to a distinct, as-yet-unidentified nocistatin receptor, which remains one of the open questions in the field.
Nocistatin is an endogenous human peptide and a research tool, not a medicine. No published study has given nocistatin to people as a treatment — the human side is its presence in brain and spinal fluid, and the functional work is in animals and cells — it is approved nowhere, and material sold online as ‘nocistatin’ is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
Nocistatin is cut from the prepronociceptin precursor, the same protein that yields nociceptin, but acts against it. It blocks nociceptin-induced pain, suppresses feeding, protects learning and memory, and modulates sensory channels and smooth-muscle tone — through a receptor that is not the nociceptin receptor and has not yet been identified.
Anti-nociceptin pain modulation
Given into the spinal fluid, nocistatin blocks the allodynia and hyperalgesia nociceptin causes and blunts inflammatory pain (PMID 9521323); at the sensory-neuron level it sensitizes the TRPA1 channel (PMID 27362459). Its active core is a conserved C-terminal hexapeptide.
Feeding, learning and memory
Nocistatin suppresses food intake and blocks nociceptin-induced overeating (PMID 10924690) and counteracts the learning-and-memory impairment caused by nociceptin or scopolamine (PMID 10998544) — opposing nociceptin across central functions.
An unidentified receptor
Nocistatin does not bind the nociceptin (NOP) receptor, yet binds brain and spinal-cord membranes with high affinity and produces pertussis-toxin-sensitive effects — evidence for a distinct, still-unidentified G-protein-coupled nocistatin receptor (PMID 25345611).
Published Research
These are studies of nocistatin read from their PubMed abstracts on November 6, 2026. They include the Nature discovery paper showing nocistatin blocks nociceptin-induced allodynia and hyperalgesia, two reviews of the peptide and its biology, a cell study of how it sensitizes the TRPA1 channel, an animal study of its appetite-suppressing effect, and an isolated-tissue study of its effect on uterine contractions. Nocistatin has not been given to people as a treatment in any published study; the human evidence is its presence in brain and cerebrospinal fluid.
Discovery: nocistatin blocks nociceptin-induced pain
The discovery paper. A second bioactive peptide, named nocistatin, was found in the nociceptin precursor and isolated from bovine brain. Given into the spinal fluid of rodents, nocistatin blocked the allodynia and hyperalgesia that nociceptin causes and attenuated prostaglandin-E2 pain; the activity lay in its conserved C-terminal hexapeptide. Anti-nocistatin antibody lowered the threshold for nociceptin allodynia. Nocistatin did not bind the nociceptin receptor but bound brain and spinal-cord membranes with high affinity — a new peptide opposing nociceptin in pain (an animal and binding study).
Nocistatin, a novel peptide from the N/OFQ precursor
A review of nocistatin as a bioactive peptide from the prepronociceptin precursor, present in spinal cord, brain and human cerebrospinal fluid. It blocks the allodynia and hyperalgesia induced by nociceptin and by prostaglandin E2, attenuates inflammatory hyperalgesia from formalin or carrageenan, reverses nociceptin’s blunting of morphine analgesia at picogram doses, and counteracts the learning and memory impairment caused by nociceptin or scopolamine — the activity residing in the conserved C-terminal hexapeptide.
Nocistatin: a decade of research
A review summarising ten years of work on nocistatin and its relationship to nociceptin. Across in-vivo, ex-vivo and in-vitro methods — knockout mice, electrophysiology, immunohistology, affinity chromatography and energy-transfer assays — nocistatin was shown to have effects opposite to nociceptin on many central functions, and the review focuses on the molecular and cellular mechanisms of pain transmission regulated by the two peptides.
Nocistatin sensitizes the TRPA1 channel
In cultured mouse sensory neurons (dorsal root ganglia), nocistatin sensitized TRPA1 — the ion channel that detects irritants such as mustard oil — increasing TRPA1-dependent calcium responses, while leaving the heat-sensing TRPV1 channel unaffected. The effect appeared independent of the proposed nocistatin binding partner NIPSNAP1, revealing a route by which nocistatin can modulate pain signalling at the sensory-neuron level (a cell-culture result).
Nocistatin inhibits food intake in rats
Injected into the brain of food-deprived rats, nocistatin reduced food intake in the first two hours and suppressed the overeating normally provoked by nociceptin, without causing conditioned taste aversion and without activating the hypothalamic oxytocin and vasopressin ‘satiety’ neurons. The work showed nocistatin opposes nociceptin’s feeding effect through a distinct mechanism (a preclinical result).
Nocistatin relaxes the pregnant rat uterus
In isolated pregnant rat uterus, nocistatin — whose levels rose in the uterus by late pregnancy — inhibited prostaglandin- and potassium-evoked contractions dose-dependently, an effect involving calcitonin-gene-related peptide, calcium-dependent potassium channels and raised cAMP, and modulated by nociceptin and naloxone. It showed nocistatin generated locally in the uterus can relax smooth muscle (an isolated-tissue result).
No Established Human Dose
Nocistatin is an endogenous human peptide that has never been given to people as a treatment. The human evidence is its presence in brain and cerebrospinal fluid; the functional studies are in animals and cells, where it is injected into the brain or spinal fluid or applied to tissues at experimental amounts that do not carry over to people. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 9521323, PMID 10924690, PMID 25345611.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Nocistatin (NST) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Nocistatin (NST) has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Nocistatin (NST), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Nocistatin (NST) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Nocistatin (NST). What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans as a drug; an endogenous signalling peptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Nocistatin (NST). Results reported in the studies are under Published Research.
Source: half-life: PMID 10998544.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered nocistatin to people; In animals it suppresses feeding (PMID 10924690) and modulates pain and sensory channels (PMIDs 9521323, 27362459) — effects of a signalling peptide, not a safety profile; Its effects in animals appear over narrow, sometimes very low (picogram) dose ranges rather than scaling simply with amount (PMID 10998544); Material sold online as ‘nocistatin’ is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Nocistatin (NST). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Nocistatin is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of Nocistatin (NST) (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Nocistatin (NST) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for nocistatin (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Nocistatin is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
Nocistatin has no approved use and no label. These points reflect its endogenous, research status.
Legal Status
Nocistatin is an endogenous human peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is nocistatin?
An endogenous human peptide cut from prepronociceptin — the same precursor that makes nociceptin (orphanin FQ). Despite the shared origin, nocistatin largely opposes nociceptin, and its active part is a short, conserved C-terminal hexapeptide.
?What does it do?
It blocks the touch-pain (allodynia) and heightened pain (hyperalgesia) that nociceptin causes and blunts inflammatory pain (PMID 9521323), suppresses feeding (PMID 10924690), protects learning and memory (PMID 10998544) and modulates sensory channels and smooth muscle (PMIDs 27362459, 23792038).
?What receptor does it act on?
Not the nociceptin (NOP) receptor — nocistatin does not bind it. It binds brain and spinal-cord membranes with high affinity and acts through a G-protein-coupled receptor, but that receptor has never been identified (PMID 25345611).
?Is it a treatment, or available to buy?
No. Nocistatin is a research peptide, not a medicine; it has no FDA application or label and is approved nowhere, and no human trial has administered it. Material sold online as nocistatin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source.
References
- [mechanism] Okuda-Ashitaka E, et al. "Nocistatin, a peptide that blocks nociceptin action in pain transmission." Nature, 1998;392(6673):286-9. PMID: 9521323.
- [review] Okuda-Ashitaka E, et al. "Nocistatin: a novel neuropeptide encoded by the gene for the nociceptin/orphanin FQ precursor." Peptides, 2000;21(7):1101-9. PMID: 10998544.
- [review] Okuda-Ashitaka E, et al. "Nocistatin: milestone of one decade of research." Curr Pharm Des, 2015;21(7):868-84. PMID: 25345611.
- [mechanism] Avenali L, et al. "Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons." Channels (Austin), 2017;11(1):11-19. PMID: 27362459.
- [animal] Olszewski PK, et al. "Nocistatin inhibits food intake in rats." Brain Res, 2000;872(1-2):181-7. PMID: 10924690.
- [mechanism] Deák BH, et al. "Nocistatin inhibits pregnant rat uterine contractions in vitro: roles of calcitonin gene-related peptide and calcium-dependent potassium channel." Eur J Pharmacol, 2013;714(1-3):96-104. PMID: 23792038.
- [other] UniProt Q13519 (PNOC_HUMAN), read November 6, 2026: nocistatin is a peptide cut from prepronociceptin, the product of the PNOC gene, which is the same precursor that yields nociceptin / orphanin FQ; the human nocistatin peptide is 30 amino acids. https://www.uniprot.org/uniprotkb/Q13519/entry
- [other] Nocistatin was discovered as a second bioactive peptide in the nociceptin / orphanin FQ precursor and isolated from bovine brain; its allodynia-blocking activity lies in the conserved C-terminal hexapeptide Glu-Gln-Lys-Gln-Leu-Gln, and it does not bind the nociceptin receptor (the discovery paper carded on this page, read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for nocistatin. It is an endogenous human peptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (Q13519, gene PNOC); nocistatin’s origin in the nociceptin precursor, its conserved C-terminal hexapeptide, its opposition to nociceptin and the unidentified status of its receptor are from the discovery paper and reviews carded here; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.