Adrenorphin (Metorphamide)
The body's own amidated opioid peptide from proenkephalin — the only natural opioid peptide with high mu-receptor affinity. A research molecule, not a drug
Adrenorphin — also called metorphamide — is a short opioid peptide the body makes itself. It is an eight-amino-acid fragment (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2) cut from proenkephalin A, the same precursor protein that gives rise to the enkephalins, and capped with an amide group at its tail. Two groups isolated it independently in 1983 — one from bovine brain (naming it metorphamide), one from a human adrenal tumour (naming it adrenorphin) — and it turned out to be the same molecule. What made it stand out is its receptor profile: of all the opioid peptides the body produces, adrenorphin is the one with high affinity for the mu-opioid receptor (the morphine receptor), with moderate kappa and negligible delta activity. In animals, injected adrenorphin produces strong, naloxone-reversible pain relief and, at higher doses, the breathing suppression characteristic of mu-opioid drugs. It is found throughout the brain — concentrated in the striatum, hypothalamus and olfactory bulb — and in the adrenal medulla. It is studied as a piece of the body's endogenous opioid system; it is not a medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Adrenorphin (metorphamide) is a peptide the body makes; it has never been given to people as a treatment. The work is in animals and tissue, where synthetic peptide is injected into the brain or spinal space at experimental amounts that do not carry over to people.
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What is it?
The body makes a family of opioid peptides from three precursor proteins — proenkephalin, prodynorphin and proopiomelanocortin. Adrenorphin, better known in the neuroscience literature as metorphamide, is one of the proenkephalin products: an eight-amino-acid peptide, Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2, that begins with the Met-enkephalin sequence and ends in an amide group. It was isolated and sequenced in 1983, from bovine brain and from human adrenal (pheochromocytoma) tissue, by two groups who gave it two names for the same molecule.
Its defining feature is its receptor profile. Most endogenous opioid peptides prefer the delta or kappa receptors; adrenorphin is the one natural opioid peptide identified with HIGH affinity for the mu-opioid receptor — the receptor through which morphine acts — alongside moderate kappa affinity and very little delta activity. The C-terminal amide, formed from a terminal glycine, protects it from carboxypeptidase and is part of what mu-receptor binding and some antibodies recognise.
In live animals, synthetic adrenorphin behaves like a mu-opioid. Given into the brain ventricles or the spinal space it inhibits reflexes and produces analgesia that naloxone reverses but a delta-selective blocker does not; comparison with other proenkephalin fragments showed the activity is the peptide's own, not a breakdown product. In mice and rabbits it produces dose-dependent, naloxone-reversible analgesia and respiratory depression, with the analgesia traced to mu-1 receptors.
It is distributed widely but unevenly. Radioimmunoassay mapping found it throughout the brain — most concentrated in the olfactory bulb, striatum and hypothalamus, with immunoreactive cell bodies in the arcuate nucleus — and in the adrenal medulla, where it is stored in chromaffin granules. Its levels there rise sharply (several-fold) after reserpine, which depletes catecholamines, pointing to coordinated control of peptide processing and amidation in the secretory vesicle.
Adrenorphin is a piece of the body's own opioid machinery, studied to understand how proenkephalin peptides act. No published study has given adrenorphin or metorphamide to people as a treatment — the evidence is animal and tissue work — it is approved nowhere, and anything sold online under either 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
Adrenorphin (metorphamide) is an amidated proenkephalin-A octapeptide that acts as an endogenous mu-opioid agonist. Unusually among the body's opioid peptides it has high mu-receptor affinity, and in animals it produces naloxone-reversible analgesia and respiratory depression. It is stored in brain neurons and adrenal chromaffin granules.
Mu-opioid agonism
Binds the mu-opioid (morphine) receptor with high affinity, moderate kappa and negligible delta; analgesia maps to mu-1 receptors and is reversed by naloxone (PMIDs 6316361, 4000426).
Proenkephalin processing
Released from proenkephalin A by cleavage at a single arginine and C-terminal amidation of a glycine; its granule levels are controlled alongside enkephalin processing (PMIDs 6316361, 3958720).
CNS and adrenal distribution
Found across the brain — olfactory bulb, striatum, hypothalamus (arcuate neurons) — and in adrenal chromaffin granules, in a pattern distinct from other opioid peptides (PMIDs 2860609, 3612117).
Published Research
These are studies of adrenorphin (metorphamide) read from their PubMed records on November 7, 2026: the 1983 discovery paper establishing its structure and high mu-opioid affinity; in-vivo animal studies of its analgesia, spinal/supraspinal opioid activity and respiratory depression; brain-distribution mapping in cattle and rats; and a chromaffin-cell study of how its levels are controlled. Adrenorphin has not been given to people as a treatment; the evidence is animal and tissue work.
Discovery: isolation, structure and opioid activity of metorphamide
An amidated opioid octapeptide, Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2, was purified from bovine caudate nucleus, sequenced, and named metorphamide. It is derived from proenkephalin by cleavage at a single arginine and C-terminal amidation, and in binding and bioassays had high mu-opioid activity (kappa ~50% of mu, delta negligible) — the only naturally occurring opioid peptide with high mu-binding activity (a discovery and characterisation study).
Metorphamide shows supraspinal and spinal mu-opioid activity in vivo
Synthetic metorphamide injected into the brain ventricles or the spinal intrathecal space inhibited reflex contractions of the rat urinary bladder; the effect was reversed by naloxone but not by a delta-opioid antagonist, and comparison with other proenkephalin-A fragments indicated the activity was the peptide's own — evidence of potent in-vivo mu-opioid, not delta, activity (a preclinical result).
Analgesic and respiratory-depressant actions of metorphamide (mice, rabbits)
Metorphamide produced potent, dose-dependent, naloxone-reversible analgesia and respiratory depression in mice and rabbits; a relatively mu-1-selective blocker abolished the analgesia but not the respiratory depression, suggesting mu-1 receptors mediate the pain relief while the respiratory effect involves mu-2 or kappa sites (a preclinical result).
Brain distribution of metorphamide vs other opioid peptides (cattle)
By radioimmunoassay and chromatography, metorphamide was present in bovine caudate nucleus, hypothalamus, spinal cord and pituitary at concentrations lower than other proenkephalin-derived opioids but similar to prodynorphin-derived ones; the amounts, with its mu-receptor binding, were judged sufficient to make it a candidate physiological mu-opioid ligand (a tissue-mapping study).
Adrenorphin immunoreactivity in rat brain
A specific radioimmunoassay, verified against authentic peptide by HPLC, found adrenorphin distributed widely but in a pattern distinct from other endogenous opioids — most concentrated in the olfactory bulb, then hypothalamus and striatum — with immunoreactive neurons in the arcuate nucleus and fibre plexuses across the hypothalamus, suggesting a distinct physiological role (a distribution study).
Reserpine raises metorphamide levels in chromaffin cells
In cultured bovine chromaffin cells, reserpine caused a dose- and time-dependent rise in metorphamide (up to ~800% of control), several-fold more than Met- or Leu-enkephalin, shifting the Met-enkephalin:metorphamide ratio toward that seen in CNS neurons — indicating reserpine stimulates enkephalin processing and amidation in the secretory vesicle (a cell study).
No Established Human Dose
Adrenorphin (metorphamide) is a peptide the body makes; it has never been given to people as a treatment. The work is in animals and tissue, where synthetic peptide is injected into the brain or spinal space 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 6316361, PMID 3839922, PMID 4000426.
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 Adrenorphin (Metorphamide) 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 Adrenorphin (Metorphamide) 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 Adrenorphin (Metorphamide), 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 Adrenorphin (Metorphamide) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Adrenorphin (Metorphamide). 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 subject to rapid peptidase cleavage. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Adrenorphin (Metorphamide). Results reported in the studies are under Published Research.
Source: half-life: PMID 6316361.
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 adrenorphin/metorphamide to people; In animals it is a mu-opioid agonist, producing analgesia and — at higher doses — respiratory depression (PMID 4000426), the characteristic and potentially dangerous opioid effect; As a mu-opioid, the class risks of tolerance, dependence and sedation would be expected concerns — a mechanistic inference, not human data for this peptide; Material sold online as 'adrenorphin' or 'metorphamide' 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 Adrenorphin (Metorphamide). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Adrenorphin 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 opioid pharmacology”).
Interactions
Unknown: a PubMed search for human interaction studies of Adrenorphin (Metorphamide) (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 Adrenorphin (Metorphamide) 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 adrenorphin or metorphamide (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
Adrenorphin 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 opioid pharmacology.
Contraindications & Cautions
Adrenorphin has no approved use and no label. These points reflect its research status.
Legal Status
Adrenorphin (metorphamide) is an endogenous opioid peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is adrenorphin?
An eight-amino-acid opioid peptide (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2) the body makes from proenkephalin A. It is also called metorphamide — two 1983 groups isolated the same molecule and gave it two names.
?Why is it notable?
It is the only endogenous opioid peptide identified with high affinity for the mu-opioid receptor — the one morphine acts on — with moderate kappa and negligible delta activity (PMID 6316361).
?What does it do in animals?
Injected into the brain or spinal space it produces naloxone-reversible analgesia and, at higher doses, respiratory depression — the behaviour of a mu-opioid agonist (PMIDs 3839922, 4000426).
?Is it approved or available to buy?
No. Adrenorphin/metorphamide is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online under either name is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Weber E, et al. "Metorphamide: isolation, structure, and biologic activity of an amidated opioid octapeptide from bovine brain." Proc Natl Acad Sci U S A, 1983;80(23):7362-6. PMID: 6316361.
- [animal] Dray A, et al. "The proenkephalin A fragment metorphamide shows supraspinal and spinal opioid activity in vivo." Peptides, 1985;6(2):217-21. PMID: 3839922.
- [animal] Xu SF, et al. "The analgesic and respiratory depressant actions of metorphamide in mice and rabbits." Neuropeptides, 1985;6(2):121-31. PMID: 4000426.
- [animal] Sonders M, et al. "Distribution pattern of metorphamide compared with other opioid peptides from proenkephalin and prodynorphin in the bovine brain." J Neurochem, 1987;49(3):671-80. PMID: 3612117.
- [animal] Miyata A, et al. "Adrenorphin immunoreactivity in rat brain." Neuropeptides, 1985;5(4-6):517-20. PMID: 2860609.
- [mechanism] Eiden LE, et al. "Metorphamide levels in chromaffin cells increase after treatment with reserpine." J Neurochem, 1986;46(5):1651-4. PMID: 3958720.
- [uniprot] UniProt P01210 (PENK_HUMAN), proenkephalin-A: the precursor protein from which adrenorphin (metorphamide) is cleaved. The mature octapeptide Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2 is released by cleavage at a single arginine residue and C-terminal amidation of a glycine, as described in the discovery paper carded on this page (read November 7, 2026).
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no application and no label record for adrenorphin or metorphamide. It is an endogenous opioid 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. Adrenorphin's structure (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2), its origin from proenkephalin A, its high mu-opioid affinity, its in-vivo analgesia and respiratory depression, and its brain and adrenal distribution are from the discovery paper and the animal and tissue 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. 'Adrenorphin' and 'metorphamide' are two names for the same peptide. 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.