Spinorphin
An endogenous peptide from spinal cord that protects enkephalins, calms inflammation, and potently blocks the P2X3 pain receptor. A research molecule, not a drug
Spinorphin is a seven-amino-acid peptide (Leu-Val-Val-Tyr-Pro-Trp-Thr) first isolated from bovine spinal cord, where it appears to act as a natural neuromodulator. Its sequence is a fragment of the hemoglobin beta-chain, so it is also a member of the hemorphin family. Spinorphin has three overlapping jobs. First, like opiorphin and sialorphin it inhibits the enzymes that break down enkephalins — among them aminopeptidase, dipeptidyl peptidase III, angiotensin-converting enzyme and enkephalinase — so it protects the body's own opioid peptides and has an antinociceptive (pain-relieving) effect. Second, it is anti-inflammatory: it blocks the fMLP receptor on neutrophils, damping their chemotaxis and activation. Third, and strikingly, it is one of the most potent known antagonists of the ATP-gated P2X3 receptor, a key channel in pain sensation. Researchers have built analogs — the DPP-III-selective tynorphin, and modified spinorphins with anticonvulsant activity — to explore these actions. Spinorphin is studied as an endogenous regulator of pain and inflammation; 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
Spinorphin is a peptide the body makes; it has never been given to people as a treatment. The work is in cells, tissue and animals, where synthetic peptide is applied at experimental amounts that do not carry over to people.
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What is it?
Spinorphin was isolated from bovine spinal cord by Japanese researchers searching for natural regulators of enkephalin breakdown. The molecule they found and named — for its spinal-cord origin — is the heptapeptide Leu-Val-Val-Tyr-Pro-Trp-Thr. Its sequence is a fragment of the hemoglobin beta-chain, which also makes it a hemorphin, one of the family of opioid-active peptides released from hemoglobin.
Its first-described role is as an endogenous inhibitor of enkephalin-degrading enzymes. The discovery work showed spinorphin inhibits several of them — aminopeptidase, a dipeptidyl aminopeptidase, angiotensin-converting enzyme and enkephalinase — from brain tissue, while sparing the same enzymes from kidney and blood, suggesting a selective neuromodulatory role. Later work pinned its strongest activity on dipeptidyl peptidase III. By protecting enkephalins from breakdown, spinorphin potentiates endogenous opioid signalling and has antinociceptive effects, and a synthetic analog, tynorphin, was made as an even stronger DPP-III inhibitor.
In rat hippocampal slices, spinorphin potentiated the facilitatory effect of enkephalin on synaptic field potentials at low stimulation frequencies — consistent with preventing enkephalin degradation — while at high frequencies it inhibited synaptic transmission and blocked long-term potentiation by a separate, use-dependent mechanism. So its effect on neural signalling is dual and context-dependent.
Spinorphin is also an inflammation regulator. In human neutrophils it suppressed chemotaxis, the respiratory burst (superoxide generation) and enzyme release triggered by the bacterial peptide fMLP, and it did so by blocking fMLP binding to its receptor — an effect other neuropeptides did not share — lowering the downstream calcium signal. A review of spinorphin framed it as an endogenous anti-inflammatory and anti-nociceptive regulator, noting it also inhibited bradykinin-induced pain responses by a mechanism different from morphine's and reduced neutrophil accumulation in an inflammation model.
Perhaps its most remarkable property emerged later: spinorphin is a potent and selective non-competitive antagonist of the ATP-gated P2X3 receptor, a purinergic channel central to pain signalling, acting at extraordinarily low concentrations. Structure-activity work mapped which residues carry this activity, and separate chemistry produced N-modified spinorphin analogs with anticonvulsant activity in mice. Throughout, spinorphin is an endogenous peptide and a research tool. No published study has given it to people as a treatment, it is approved nowhere, and anything sold online under its name is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says.
Mechanism of Action
Spinorphin is a hemoglobin-derived heptapeptide with three overlapping actions: it inhibits enkephalin-degrading enzymes (especially dipeptidyl peptidase III) to protect endogenous enkephalins, it blocks the neutrophil fMLP receptor to damp inflammation, and it potently antagonises the ATP-gated P2X3 pain receptor.
Enkephalinase inhibition
Inhibits aminopeptidase, dipeptidyl peptidase III, ACE and enkephalinase, protecting enkephalins and producing antinociception (PMIDs 8230703, 12470213).
Anti-inflammatory (fMLP receptor)
Blocks fMLP binding on neutrophils, suppressing chemotaxis, superoxide burst and enzyme release (PMID 9310346).
P2X3 antagonism
A potent, selective non-competitive antagonist of the ATP-gated P2X3 receptor, a key pain channel (PMID 17676725).
Published Research
These are studies of spinorphin read from their PubMed records on November 7, 2026: the discovery paper identifying it as an enkephalinase-inhibitor heptapeptide from spinal cord; work on its anti-inflammatory action on neutrophils and its effects on hippocampal synaptic transmission; a review of its roles in pain and inflammation; the discovery of its potent P2X3-receptor antagonism; and anticonvulsant spinorphin analogs. The evidence is in cells, tissue and animals; spinorphin has not been given to people as a treatment.
Discovery: spinorphin, an enkephalinase-inhibitor peptide from spinal cord
A potent inhibitor of enkephalin-degrading enzymes was isolated from bovine spinal cord and its sequence determined as the heptapeptide Leu-Val-Val-Tyr-Pro-Trp-Thr; it inhibited aminopeptidase, dipeptidyl aminopeptidase, angiotensin-converting enzyme and enkephalinase from brain while sparing those from kidney and blood, and was named spinorphin and proposed as a spinal-cord-derived neuromodulator (a discovery study).
Spinorphin inhibits neutrophil activation by blocking the fMLP receptor
In human neutrophils, spinorphin inhibited chemotaxis, superoxide generation and enzyme exocytosis triggered by the bacterial peptide fMLP; it did so by suppressing fMLP binding to its receptor (an effect angiotensin II and substance P did not share) and the resulting calcium signal, suggesting spinorphin is an endogenous inflammation-regulatory peptide (an in-vitro study).
Spinorphin's dual effects on hippocampal synaptic transmission (rat)
In rat hippocampal slices, spinorphin potentiated the facilitatory effect of enkephalin on field potentials at a low stimulation frequency (consistent with preventing enkephalin breakdown) but, at high frequency, inhibited transmission use-dependently and blocked long-term potentiation by a separate mechanism — a dual, context-dependent action (an ex-vivo study; the analog tynorphin potentiated enkephalin without the use-dependent block).
Spinorphin in pain and inflammation (review)
A review of spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes (strongest against dipeptidyl peptidase III): it inhibits bradykinin-induced nociceptive responses by a mechanism distinct from morphine's, suppresses neutrophil function via the fMLP receptor, and reduces neutrophil accumulation in an inflammation model — framing it as an endogenous anti-nociceptive and anti-inflammatory regulator.
Spinorphin is a potent, selective P2X3-receptor antagonist
Against recombinant human P2X3 receptors expressed in Xenopus oocytes, spinorphin (LVVYPWT) was a potent non-competitive antagonist acting at picomolar concentrations; alanine-scanning and a cyclic form kept the antagonism, while a C-terminal threonine-to-alanine change instead enhanced agonist activity — mapping the structural basis of its P2X3 block (a mechanistic study).
N-modified spinorphin analogs show anticonvulsant activity (mice)
Newly synthesised N-modified (rhodamine-tagged) spinorphin analogs were characterised and screened for bioactivity; two analogs had anticonvulsant effects comparable to the parent against psychomotor and chemically induced seizures in mice, alongside modest antioxidant activity — illustrating spinorphin-based analog development (a preclinical result).
No Established Human Dose
Spinorphin is a peptide the body makes; it has never been given to people as a treatment. The work is in cells, tissue and animals, where synthetic peptide is applied 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 8230703, PMID 9310346, PMID 17676725.
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 Spinorphin 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 Spinorphin 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 Spinorphin, 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 Spinorphin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Spinorphin. 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; a small endogenous 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 Spinorphin. Results reported in the studies are under Published Research.
Source: half-life: PMID 11226390.
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 spinorphin to people; Its actions span opioid potentiation, anti-inflammatory and P2X3-blocking effects — broad biology that would need careful study, an inference, not human safety data; In rat hippocampus it blocked long-term potentiation at high stimulation frequencies (PMID 11226390), a reminder its effects on neural signalling are context-dependent; Material sold online as 'spinorphin' 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 Spinorphin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Spinorphin 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 and its biology”).
Interactions
Unknown: a PubMed search for human interaction studies of Spinorphin (reviewed 2026-11-07) 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 Spinorphin 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 drug record for spinorphin (searched November 7, 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
Spinorphin 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 and its biology.
Contraindications & Cautions
Spinorphin has no approved use and no label. These points reflect its research status.
Legal Status
Spinorphin is an endogenous peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is spinorphin?
A seven-amino-acid peptide (Leu-Val-Val-Tyr-Pro-Trp-Thr) isolated from spinal cord. Its sequence is a hemoglobin-beta fragment, so it is also a hemorphin. It inhibits enkephalin-degrading enzymes.
?What does it do?
Three things: it protects enkephalins (antinociception), it damps neutrophil inflammation by blocking the fMLP receptor, and it is a potent antagonist of the P2X3 pain receptor (PMIDs 8230703, 9310346, 17676725).
?How does it relate to opiorphin and sialorphin?
All three are endogenous inhibitors of enkephalin-degrading enzymes that boost the body's own opioid signalling. Spinorphin is hemoglobin-derived and additionally blocks the P2X3 receptor.
?Is it approved or available to buy?
No. Spinorphin is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as spinorphin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Nishimura K, et al. "[Spinorphin, a new inhibitor of enkephalin-degrading enzymes derived from the bovine spinal cord]." Masui, 1993;42(10):1497-503. PMID: 8230703.
- [mechanism] Yamamoto Y, et al. "Inhibitory effects of spinorphin, a novel endogenous regulator, on chemotaxis, O2- generation, and exocytosis by N-formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils." Biochem Pharmacol, 1997;54(6):695-701. PMID: 9310346.
- [mechanism] Yamazaki T, et al. "Effects of spinorphin and tynorphin on synaptic transmission in rat hippocampal slices." Eur J Pharmacol, 2001;413(2-3):173-8. PMID: 11226390.
- [review] Yamamoto Y, et al. "Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes: roles in pain and inflammation." Curr Protein Pept Sci, 2002;3(6):587-99. PMID: 12470213.
- [mechanism] Jung KY, et al. "Structure-activity relationship studies of spinorphin as a potent and selective human P2X(3) receptor antagonist." J Med Chem, 2007;50(18):4543-7. PMID: 17676725.
- [animal] Todorov P, et al. "Synthesis, Characterization and Biological Investigation of New N-Modified Spinorphin Analogs." Pharmaceuticals (Basel), 2022;15(10). PMID: 36297364.
- [other] Spinorphin is the heptapeptide Leu-Val-Val-Tyr-Pro-Trp-Thr (LVVYPWT), isolated from bovine spinal cord and identified as an endogenous inhibitor of enkephalin-degrading enzymes, as described in the discovery paper carded on this page (read November 7, 2026). Its sequence corresponds to a fragment of the hemoglobin beta-chain, placing it in the hemorphin family of hemoglobin-derived peptides.
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no application and no label record for spinorphin. It is an endogenous peptide studied in research, not a drug; FDA GSRS and ChEMBL hold no drug record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 7, 2026. Spinorphin's structure (LVVYPWT), its hemoglobin-beta origin and isolation from spinal cord, its inhibition of enkephalin-degrading enzymes (especially DPP III), its anti-inflammatory action on neutrophils, its dual effects on hippocampal transmission, its potent P2X3 antagonism and its anticonvulsant analogs are from the discovery paper, review and mechanistic and animal studies carded here; the absence of US approval or a drug 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.