Deltorphin
A family of frog-skin peptides that are the most selective natural switches for the delta-opioid receptor; unusual for carrying a D-amino acid, they cross into the brain and are classic tools for studying opioid pain relief
The opioid system has three main receptors — mu, delta and kappa. Morphine and most opioid drugs act mainly on the mu receptor, which brings pain relief but also the euphoria, dependence and breathing risk that make opioids dangerous. The delta receptor is a different target that researchers have long hoped could give analgesia and mood benefits with fewer of those liabilities, and to study it they needed a probe that hits delta and nothing else. The deltorphins, discovered in the skin of South American Phyllomedusa frogs, are exactly that: the most delta-selective natural peptides known. They are also chemically odd — each carries a D-amino acid, the mirror-image form almost never seen in animal peptides — and they slip across the blood-brain barrier unusually well. Deltorphins are research tools in opioid pharmacology, not medicines; they have never been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
The deltorphins are amphibian research peptides, not treatments, and no human dose exists. They have been used only in laboratory and animal studies of the delta-opioid receptor, never given to people for any condition, and no regulator has approved a dose.
Work out syringe units → · New to syringes? · All dosing data ↓ · Dose and vial tracker · Is this vial OK?
What is it?
In the late 1980s, Vittorio Erspamer's group, famous for mining frog and toad skin for active peptides, was working out the gene for dermorphin, a potent mu-opioid peptide from the waxy monkey frog Phyllomedusa sauvagei. The gene's sequence hinted at a second, related peptide. When they made it, one version — built with a D-methionine in the second position — bound the delta-opioid receptor with remarkable selectivity, and they then isolated the natural peptide from frog skin and confirmed it really did contain that D-amino acid. They named it deltorphin, for its delta selectivity.
Two close relatives, deltorphin I and deltorphin II, were found in a sibling frog, Phyllomedusa bicolor; they share the structure Tyr-D-Ala-Phe-(Asp or Glu)-Val-Val-Gly-NH2. All the deltorphins have two features that make them prized probes. First, their delta-opioid selectivity is extreme — they activate the delta receptor at far lower concentrations than the mu or kappa receptors — so they can be used to ask what the delta receptor alone does. Second, the D-amino acid makes them resist the peptide-chewing enzymes that destroy ordinary peptides, which is part of why they last long enough to be useful.
Deltorphins also cross the blood-brain barrier unusually well. A study in isolated brain microvessels showed they are carried across by a specific, saturable transport system distinct from the routes used by amino acids or enkephalins, which helps explain their strong effects when given outside the brain. In animals, deltorphin analogues produce analgesia that is reversed by delta-selective blockers, confirming the effect runs through the delta receptor, and newer medicinal-chemistry work has tuned the peptide — for example adding halogens — to make better-behaved delta agonists and radioligands.
The delta receptor is not only about pain. Deltorphin II, infused into the reward circuitry of the rat brain, raised dopamine in the nucleus accumbens, linking delta signalling to the brain's reward system, though by a route that turned out not to depend simply on the classic opioid receptor. And in a more surprising direction, deltorphin-II slowed the development of malaria in infected mice, an antimicrobial-style effect blocked by a delta antagonist — a reminder that these peptides reach beyond neuroscience.
For all their usefulness in the laboratory, the deltorphins are research compounds. They are the tools that helped define what the delta-opioid receptor does and inspired efforts to make delta-selective painkillers, but deltorphin itself is approved nowhere, has never been given to people as a treatment, and what is sold online as ‘deltorphin’ is an unregulated research chemical. Nothing here is a dose or a therapy; this page records the published science on a landmark family of opioid research peptides.
Mechanism of Action
Deltorphins are selective keys for the delta-opioid receptor. Their D-amino acid and shape let them switch on delta signalling with little effect on the mu and kappa receptors, and a dedicated transporter carries them into the brain.
Delta-opioid selectivity
The deltorphins activate the delta-opioid receptor at far lower concentrations than the mu or kappa receptors, with the C-terminal tripeptide driving that selectivity (PMIDs 2542051, 1331451) — the property that made them the standard natural delta probes.
D-amino acid for stability
Each deltorphin carries a D-amino acid in position 2 (D-Met or D-Ala), a mirror-image residue almost unknown in animal peptides that resists the enzymes which rapidly destroy ordinary peptides (PMID 2542051), prolonging their action.
Brain entry and effects
A dedicated saturable transporter carries deltorphins across the blood-brain barrier (PMID 9256506), where delta activation produces analgesia (PMID 25844930) and engages reward circuitry by raising accumbal dopamine (PMID 15102530).
Published Research
These are studies of the deltorphins read from their PubMed abstracts on November 5, 2026. They run from the 1989 discovery of a delta-selective amphibian peptide, through its blood-brain-barrier transport, structure-activity work defining delta selectivity, analgesic halogenated analogues and a dopamine-releasing effect, to an unexpected antimalarial action. The work is entirely preclinical — deltorphins have not been given to people.
Discovery of a delta-selective frog peptide
Working from the dermorphin gene, the authors predicted and synthesised a related peptide; the version with D-methionine in position 2 bound the delta-opioid receptor with high affinity and selectivity in mouse vas deferens and rat brain, and the natural D-amino-acid peptide was then isolated from Phyllomedusa sauvagei skin. They named it deltorphin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2).
Crossing the blood-brain barrier
Deltorphins penetrated the brain unusually well in vivo, and in isolated bovine brain microvessels they were taken up by a specific, saturable transport system distinct from those carrying amino acids or enkephalins. The uptake was blocked by naloxone but not by delta or mu receptor ligands and did not involve detectable opioid receptors on the vessels, defining a dedicated transport route into the brain.
Analgesic halogenated analogues
A [D-Ala2]deltorphin II-based peptide was designed to be delta-selective over mu and kappa receptors; it was a full agonist and produced analgesia in mice that was blocked by the delta-selective antagonist naltrindole, confirming a delta-mediated effect. Adding halogens at the Phe3 ring gave a series whose binding tracked with halogen size, useful probes for delta-opioid pharmacology.
Dopamine release in the reward circuit
Perfused into the rat nucleus accumbens, deltorphin II raised extracellular dopamine, linking delta-opioid signalling to the brain's reward pathway. The effect was not blocked by selective delta, mu or non-selective opioid antagonists but was largely abolished by the sodium-channel blocker tetrodotoxin, suggesting an opioid-receptor-independent, neuronal mechanism.
An antimalarial effect in mice
In malaria-infected mice, deltorphin-II reduced parasitaemia over three weeks, with maximum activity at 0.8 mg/kg/day; pre-treatment with the delta-selective antagonist naltriben abolished the effect, indicating it was mediated by the delta-opioid receptor. An unexpected, antimicrobial-style action of a peptide best known in neuroscience.
Structure and delta-selectivity
Conformationally restricted deltorphin analogues were made to probe how the peptide achieves its delta selectivity. Substitutions in the N-terminal region produced partial agonists and even a potent, highly delta-selective antagonist, while the work showed the C-terminal tripeptide segment is crucial for delta affinity and selectivity of the agonists.
No Established Human Dose
The deltorphins are amphibian research peptides, not treatments, and no human dose exists. They have been used only in laboratory and animal studies of the delta-opioid receptor, never given to people for any condition, and no regulator has approved a dose. Animal studies used them by injection or brain infusion at microgram-to-milligram-per-kilogram amounts that do not carry over to people, so no amount is printed here.
What this rests on: PMID 2542051, PMID 9256506, PMID 25844930, PMID 38779626.
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 Deltorphin 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 Deltorphin 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 Deltorphin, 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 Deltorphin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Deltorphin. 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 longer-lived than ordinary peptides; the D-amino acid resists enzymatic breakdown. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Deltorphin. Results reported in the studies are under Published Research.
Source: half-life: PMID 2542051.
Side effects, and when to stop or get help
From the Side Effects section: No human safety data exist: the deltorphins have not been administered to people; They are delta-opioid agonists; in animals delta agonists can lower seizure threshold at high doses (a class caution); Effects in animals are blocked by delta-opioid antagonists, confirming receptor-mediated actions (PMIDs 25844930, 38779626); Material sold online as ‘deltorphin’ 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 Deltorphin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“The deltorphins are research peptides never given to people, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of Deltorphin (reviewed 2026-11-05) 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 Deltorphin 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 for deltorphin (searched November 5, 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
The deltorphins are research peptides never given to people, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
Deltorphin has no approved use and no label. These points reflect its research-only status.
Legal Status
The deltorphins are amphibian research peptides studied as delta-opioid probes; they are not drugs and are not approved in any country.
Frequently Asked Questions
?What is deltorphin?
A family of peptides from the skin of Phyllomedusa frogs — deltorphin, deltorphin I and deltorphin II — that are the most selective natural agonists of the delta-opioid receptor. They are unusual for containing a D-amino acid and are used as research probes.
?What does it do?
It switches on the delta-opioid receptor with little effect on the mu or kappa receptors (PMIDs 2542051, 1331451), crosses into the brain through a dedicated transporter (PMID 9256506), and in animals produces delta-mediated analgesia (PMID 25844930) and raises reward-circuit dopamine (PMID 15102530).
?Why is the delta receptor interesting?
Most opioid drugs act on the mu receptor, which carries the risks of dependence and breathing suppression. The delta receptor is studied as a route to pain relief and mood benefit with fewer of those liabilities, and deltorphins are the classic tools for probing it — though delta drugs themselves remain investigational.
?Is it approved or available to buy?
No. Deltorphin is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as deltorphin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Kreil G, et al. "Deltorphin, a novel amphibian skin peptide with high selectivity and affinity for delta opioid receptors." Eur J Pharmacol, 1989;162(1):123-8. PMID: 2542051.
- [animal] Fiori A, et al. "Deltorphin transport across the blood-brain barrier." Proc Natl Acad Sci U S A, 1997;94(17):9469-74. PMID: 9256506.
- [animal] Pescatore R, et al. "Synthesis and pharmacology of halogenated δ-opioid-selective [d-Ala(2)]deltorphin II peptide analogues." ACS Chem Neurosci, 2015;6(6):905-10. PMID: 25844930.
- [animal] Murakawa K, et al. "Deltorphin II enhances extracellular levels of dopamine in the nucleus accumbens via opioid receptor-independent mechanisms." Eur J Pharmacol, 2004;491(1):31-6. PMID: 15102530.
- [animal] Ajitbhai GA, et al. "Inhibitory effect of deltorphin-II on development of malaria in Plasmodium berghei-infected mice." Malariaworld J, 2015;6:3. PMID: 38779626.
- [mechanism] Schiller PW, et al. "Conformationally restricted deltorphin analogues." J Med Chem, 1992;35(21):3956-61. PMID: 1331451.
- [other] PubChem, read November 5, 2026: deltorphin II, CID 10033203, C38H54N8O10, MW 782.9, sequence Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2; one of the deltorphin heptapeptides, which carry a D-amino acid in position 2. https://pubchem.ncbi.nlm.nih.gov/compound/10033203
- [other] The deltorphins were found in the skin of Phyllomedusa frogs and named in 1989 as the most delta-opioid-selective natural peptides then known; deltorphin, deltorphin I and deltorphin II share a position-2 D-amino acid, as described in the discovery paper carded on this page (read November 5, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 5, 2026: no application and no label record for deltorphin. The deltorphins are amphibian research peptides, not registered drugs; FDA GSRS and ChEMBL hold no drug substance record for them.
Sources & Citations
The six studies carded above were read from their PubMed records on November 5, 2026. Structure and identifiers come from PubChem (deltorphin II, CID 10033203); the deltorphins' 1989 discovery and their D-amino-acid delta selectivity are from the discovery paper carded here; the absence of US approval and of a drug record from Drugs@FDA and openFDA 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.