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OTHERPEPTIDE PROFILE

Dermorphin

Also known as H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, Frog Skin Opioid Peptide

Dermorphin is a heptapeptide (7 amino acids) isolated from the skin of Phyllomedusa South American tree frogs. It is a potent and selective mu-opioid receptor (MOR) agonist, estimated to be 30–40 times more potent than morphine on a molar basis. A defining structural feature is the presence of a D-amino acid (D-alanine at position 2), which is exceptionally rare in naturally occurring vertebrate peptides and confers metabolic resistance and high receptor affinity. Dermorphin gained notoriety in horse racing doping scandals in 2012.

Last updated April 10, 2026

TL;DR

Quick summary

Dermorphin is a 7-amino acid frog-skin peptide 30-40x more potent than morphine at the mu-opioid receptor. Its rare D-alanine residue confers metabolic resistance; it gained notoriety in 2012 horse racing doping scandals.

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Overview

Dermorphin is a heptapeptide (7 amino acids) isolated from the skin of Phyllomedusa South American tree frogs. It is a potent and selective mu-opioid receptor (MOR) agonist, estimated to be 30–40 times more potent than morphine on a molar basis. A defining structural feature is the presence of a D-amino acid (D-alanine at position 2), which is exceptionally rare in naturally occurring vertebrate peptides and confers metabolic resistance and high receptor affinity. Dermorphin gained notoriety in horse racing doping scandals in 2012.

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Mechanism of action

Dermorphin binds mu-opioid receptors with high affinity and selectivity, activating Gi/Go signaling to inhibit adenylyl cyclase, suppress voltage-gated calcium channels, and activate GIRK potassium channels. The result is profound neuronal inhibition in pain pathways including the dorsal horn and periaqueductal gray matter. The D-alanine residue at position 2 increases resistance to aminopeptidase cleavage, extending biological activity compared to endogenous opioid peptides. Dermorphin does not have meaningful affinity at delta or kappa opioid receptors at therapeutic concentrations.

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Dosing protocols

PurposeRouteDosageFrequency
mu-opioid receptor research / pain models (animal)intravenous0.011 mg/kgper experimental protocol
receptor binding / characterization studiesintramuscular0.0010.1 mg/kgper experimental protocol

Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.

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Research summary

Dermorphin's extreme potency and selectivity have made it a valuable pharmacological tool for opioid receptor characterization. Research applications include receptor binding studies, pain model experiments, and development of dermorphin-derived analogs with improved pharmacokinetics. Analogs such as DALDA (Tyr-D-Arg-Phe-Lys-NH2) and other modified sequences are studied for targeted analgesia. In 2012, dermorphin was detected in post-race urine samples of multiple racehorses at US tracks, leading to bans and prosecutions. No approved therapeutic applications exist for dermorphin in humans.[1][2][3]

📄This section cites 3 peer-reviewed sources. View all references →
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Evidence grading

Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.

strong
30-40x more potent than morphine at mu-opioid receptorDecades of receptor binding and in vivo potency assays consistently confirm extreme MOR potency
strong
D-alanine confers metabolic resistanceBiochemical peptidase resistance studies confirm D-Ala-2 prevents aminopeptidase cleavage
strong
Detected in horse racing doping scandals 2012Documented detection in multiple post-race urine samples at US tracks led to bans and prosecutions
strong
Selective for mu over delta/kappa receptorsReceptor binding studies confirm orders-of-magnitude selectivity for MOR over other opioid receptors
insufficient
No approved human therapeutic applicationsDespite 40+ years since discovery, no clinical development has advanced to regulatory approval

Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data

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Side effects

Profound analgesia
Respiratory depression (MOR-mediated)
Sedation
GI motility reduction
Physical dependence with repeated dosing

Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.

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Common stacks

Peptides commonly paired with Dermorphin for synergistic effects.

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Sourcing & access

Research compound

Dermorphin is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).

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Frequently asked questions

Dermorphin is a heptapeptide isolated from Phyllomedusa South American tree frogs. It is a potent and selective mu-opioid receptor agonist estimated to be 30-40 times more potent than morphine. Its defining feature is a D-amino acid (D-alanine at position 2), which is exceptionally rare in naturally occurring vertebrate peptides.

Dermorphin binds mu-opioid receptors with high affinity and selectivity, activating Gi/Go signaling to inhibit adenylyl cyclase, suppress calcium channels, and activate potassium channels, producing profound neuronal inhibition in pain pathways. The D-alanine residue increases resistance to aminopeptidase cleavage, extending its biological activity.

Dermorphin carries significant risks including profound analgesia, respiratory depression (the primary danger of mu-opioid agonists), sedation, GI motility reduction, and physical dependence with repeated dosing. It is not approved for human or veterinary therapeutic use.

In 2012, dermorphin was detected in post-race urine samples of multiple racehorses at US tracks, leading to bans and prosecutions. Its extreme potency as a pain-masking agent gave treated horses an unfair competitive advantage. It is banned by all major racing regulatory bodies.

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Research references

  1. Dermorphin: an opioid peptide from frog skin with mu-receptor selectivityMor A, Nicolas P, et al.Proc Natl Acad Sci USA, 1981PubMed
  2. Structure-activity relationships of dermorphin analogues as opioid analgesicsSalvadori S, Bianchi C, et al.J Med Chem, 1992PubMed
  3. Dermorphin peptides: pharmacological characterization and D-amino acid effectsErspamer V, Melchiorri P, et al.Peptides, 1989PubMed
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