Sialorphin
The rat version of opiorphin — a natural neprilysin inhibitor that protects the body's enkephalins and substance P. A research peptide, not a drug
Sialorphin is a five-amino-acid rat peptide (Gln-His-Asn-Pro-Arg) and the rat counterpart of human opiorphin. Like opiorphin, it is not an opioid itself: it works by inhibiting neprilysin (neutral endopeptidase, NEP), the surface enzyme that normally breaks down signalling peptides such as the enkephalins and substance P. By protecting those peptides, sialorphin prolongs their action — and in rats this produces potent pain relief that depends on mu- and delta-opioid receptors, because it lets endogenous enkephalins keep signalling. It is made in the submandibular (salivary) gland and prostate under the control of male sex hormones and is released into the blood in response to stress. Beyond pain, sialorphin became central to erectile-function research: its gene (Vcsa1) is one of the most strongly switched-off genes in rat models of erectile dysfunction, and giving sialorphin relaxes penile smooth muscle and restores erectile responses in ageing rats. It is studied as the progenitor of a potential new class of NEP-inhibitor therapeutics; 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
Sialorphin is a rat peptide that has never been given to people as a treatment. The work is in rats, mice and cells, where synthetic peptide is given by injection or into tissue at experimental amounts that do not carry over to people.
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What is it?
Sialorphin is a short rat peptide, Gln-His-Asn-Pro-Arg, identified by the Institut Pasteur group as a natural, systemically active regulator of neutral endopeptidase (neprilysin, NEP). NEP is a cell-surface enzyme that switches off peptide signals by cleaving them; sialorphin binds NEP and blocks it, so the peptides NEP would destroy — notably substance P and Met-enkephalin — persist and keep signalling. It is the rat counterpart of human opiorphin, and the two peptides share this enkephalinase-inhibiting mechanism.
In the discovery work, sialorphin was shown to bind the membrane-anchored NEP in rat kidney, to inhibit the breakdown of substance P as a competitive inhibitor, and, given intravenously, to produce potent pain relief in two rat injury-pain models (the pin-pain and formalin tests). That analgesia required mu- and delta-opioid receptors, confirming it works by protecting endogenous enkephalins rather than by acting on opioid receptors directly. Sialorphin is made under androgen control in the submandibular gland and prostate and surges into the circulation on stress, suggesting a physiological role in modulating pain and behaviour.
A 2020 pharmacology study added an important nuance: sialorphin potentiated the effects of Met-enkephalin in mouse vas deferens and in rat antinociception, and it did so even beyond what peptidase inhibitors alone achieved and without affecting opioid-receptor binding — and critically without signs of toxicity such as motor dysfunction. The authors concluded sialorphin potentiates enkephalin partly by a mechanism other than peptidase inhibition, and suggested it could reduce the side effects seen with opioid drugs.
Sialorphin's second research life is in erectile function. Its gene, Vcsa1, is among the most strongly down-regulated genes in several rat models of erectile dysfunction. Intracorporeal sialorphin relaxed penile (corporal) smooth muscle and produced a time-dependent restoration of erectile responses in ageing rats, and work on cultured corporal smooth-muscle cells showed that sialorphin — through its effect on NEP — regulates the expression of G-protein-coupled receptors, part of how it modulates erectile physiology.
Researchers have also built improved versions: N-terminally lipidated sialorphin analogs are stronger NEP inhibitors in vitro and, in a mouse model of colitis, lipidated analogs reduced intestinal inflammation — extending the enkephalin-protecting strategy to inflammatory bowel disease. Throughout, sialorphin is a rat peptide and a research tool. No published study has given sialorphin 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
Sialorphin is a rat pentapeptide and the counterpart of human opiorphin. It inhibits neutral endopeptidase (neprilysin), protecting substance P and the enkephalins from breakdown, which amplifies endogenous mu-/delta-opioid analgesia. It is androgen-regulated and also modulates erectile function via corporal smooth-muscle relaxation and receptor expression.
Neprilysin (NEP) inhibition
Competitively inhibits neutral endopeptidase, protecting substance P and Met-enkephalin from degradation, so opioid analgesia is potentiated through mu-/delta-receptors (PMID 12835417).
Androgen-regulated signalling
Made in submandibular gland and prostate under androgen control and released on stress; modulates male sexual behaviour dose-dependently (PMID 15555512).
Erectile / smooth-muscle effects
Relaxes corporal smooth muscle and restores erectile responses in ageing rats, and regulates GPCR expression via NEP; its gene is down-regulated in ED models (PMIDs 17026587, 18554633).
Published Research
These are studies of sialorphin read from their PubMed records on November 7, 2026: the 2003 discovery paper establishing it as a neprilysin inhibitor with opioid-dependent analgesia in rats; animal studies of its androgen-regulated effects on male sexual behaviour and erectile function; mechanistic work on how it regulates receptor expression and potentiates enkephalin; and lipidated analogs tested against intestinal inflammation in mice. Sialorphin has not been given to people as a treatment; the evidence is rat, mouse and cell work.
Discovery: sialorphin inhibits neprilysin and relieves pain via opioid receptors
Sialorphin was shown to bind membrane-anchored neutral endopeptidase (neprilysin) in rat kidney and to competitively inhibit its breakdown of substance P and Met-enkephalin; given intravenously it produced potent analgesia in two rat injury-pain models, an effect requiring mu- and delta-opioid receptors — establishing sialorphin as a natural NEP regulator that protects endogenous enkephalins (a discovery study).
Androgen-regulated sialorphin modulates male rat sexual behaviour
In intact male rats, sialorphin given before pairing with a receptive female modulated the mating pattern in a dose-related way — increasing intromissions and apparent sexual arousal with a dual facilitative-or-inhibitory effect on performance depending on amount — consistent with a role for this androgen-regulated peptide in balancing male sexual response (a behavioural study).
Sialorphin relaxes penile smooth muscle and restores erectile function in ageing rats
Intracorporeal sialorphin produced a time-dependent increase in the erectile (intracorporal/blood-pressure) response to cavernosal-nerve stimulation in ageing rats, reaching a ratio associated with normal function, and in organ-bath studies it markedly enhanced relaxation of corporal smooth-muscle tissue — showing a role in erectile function via smooth-muscle relaxation (a preclinical result).
Sialorphin/NEP regulates GPCR expression in corporal smooth muscle
Knocking down the sialorphin gene Vcsa1 in cultured rat corporal smooth-muscle cells up-regulated G-protein-coupled receptors as a group, while lowering NEP activity did the opposite, and in rats with transected cavernous nerves reduced Vcsa1 accompanied increased GPCR expression — indicating sialorphin modulates erectile function partly by shaping receptor expression through NEP (a mechanistic study).
Sialorphin potentiates Met-enkephalin without toxicity, beyond peptidase inhibition
In mouse vas deferens and rat antinociception, sialorphin potentiated Met-enkephalin's effects beyond what chemical peptidase inhibitors achieved and without affecting opioid-receptor binding, producing a large augmentation of enkephalin analgesia without signs of toxicity such as motor dysfunction — suggesting it acts partly by a mechanism other than peptidase inhibition and may reduce opioid side effects (an in-vitro and in-vivo study).
Lipidated sialorphin analogs inhibit NEP and reduce colitis in mice
N-terminally lipidated analogs of sialorphin were synthesised; a stearic-acid analog was the strongest in-vitro inhibitor of neprilysin's degradation of Met-enkephalin, and in a dextran-sulphate-sodium mouse model of colitis, lipidated analogs reduced intestinal inflammation — extending the enkephalin-protecting approach toward inflammatory bowel disease (a preclinical result).
No Established Human Dose
Sialorphin is a rat peptide that has never been given to people as a treatment. The work is in rats, mice and cells, where synthetic peptide is given by injection or into tissue 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 12835417, PMID 17026587, PMID 32759368.
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 Sialorphin 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 Sialorphin 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 Sialorphin, 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 Sialorphin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Sialorphin. 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 short; a small peptide, with lipidated analogs made to improve stability. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Sialorphin. Results reported in the studies are under Published Research.
Source: half-life: PMID 36430928.
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 sialorphin to people; In animals its analgesia works through endogenous opioid pathways; one study specifically reported potentiation of enkephalin without signs of toxicity such as motor dysfunction (PMID 32759368) — an animal finding, not a human safety profile; Its androgen regulation and dose-dependent, dual effects on male sexual behaviour (PMID 15555512) indicate context-dependent actions beyond analgesia; Material sold online as 'sialorphin' 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 Sialorphin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Sialorphin is an endogenous rat 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 Sialorphin (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 Sialorphin 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 sialorphin (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
Sialorphin is an endogenous rat 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
Sialorphin has no approved use and no label. These points reflect its research status.
Legal Status
Sialorphin is an endogenous rat peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is sialorphin?
A five-amino-acid rat peptide (Gln-His-Asn-Pro-Arg) and the rat counterpart of human opiorphin. It inhibits the enzyme neprilysin (NEP), protecting the body's enkephalins and substance P.
?How does it relieve pain?
Indirectly. By blocking neprilysin it stops endogenous enkephalins being broken down, so they keep activating mu- and delta-opioid receptors; in rats this produced analgesia requiring those receptors (PMID 12835417).
?Why is it linked to erectile function?
Its gene (Vcsa1) is strongly down-regulated in rat erectile-dysfunction models, and giving sialorphin relaxes penile smooth muscle and restores erectile responses in ageing rats (PMIDs 17026587, 18554633).
?Is it approved or available to buy?
No. Sialorphin is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as sialorphin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Rougeot C, et al. "Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity." Proc Natl Acad Sci U S A, 2003;100(14):8549-54. PMID: 12835417.
- [animal] Messaoudi M, et al. "The endogenous androgen-regulated sialorphin modulates male rat sexual behavior." Horm Behav, 2004;46(5):684-91. PMID: 15555512.
- [animal] Davies KP, et al. "Sialorphin (the mature peptide product of Vcsa1) relaxes corporal smooth muscle tissue and increases erectile function in the ageing rat." BJU Int, 2007;99(2):431-5. PMID: 17026587.
- [mechanism] Tong Y, et al. "Transcription of G-protein coupled receptors in corporeal smooth muscle is regulated by the endogenous neutral endopeptidase inhibitor sialorphin." J Urol, 2008;180(2):760-6. PMID: 18554633.
- [animal] Kan T, et al. "Sialorphin Potentiates Effects of [Met(5)]Enkephalin without Toxicity by Action other than Peptidase Inhibition." J Pharmacol Exp Ther, 2020;375(1):104-114. PMID: 32759368.
- [animal] Sobocińska M, et al. "N-Terminally Lipidated Sialorphin Analogs-Synthesis, Molecular Modeling, In Vitro Effect on Enkephalins Degradation by NEP and Treatment of Intestinal Inflammation in Mice." Int J Mol Sci, 2022;23(22). PMID: 36430928.
- [other] Sialorphin is the rat pentapeptide Gln-His-Asn-Pro-Arg (QHNPR), the mature product of the rat Vcsa1 gene (also called SMR1). It is synthesised mainly in the submandibular gland and prostate under androgen control and released locally and systemically on stress, as described in the discovery paper carded on this page (read November 7, 2026). It is the rat counterpart of human opiorphin.
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no application and no label record for sialorphin. It is an endogenous rat 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. Sialorphin's structure (QHNPR), its origin from the rat Vcsa1 gene, its inhibition of neprilysin and protection of substance P and enkephalin, its opioid-dependent analgesia, its androgen-regulated effects on sexual and erectile function, and the lipidated analogs are from the discovery paper and animal, cell and chemistry 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. Sialorphin is the rat counterpart of human opiorphin. 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.