Dermorphin
Also known as: Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, frog-skin opioid peptide
Not approved for any human or veterinary use; target of equine and human doping-control testing.
4 notable studies · 5 references
TLDR
Dermorphin is a seven-amino-acid opioid peptide from frog skin, containing a rare D-alanine, that strongly and selectively activates mu-opioid receptors and was far more potent than morphine in early rodent tests; it has no human clinical trials, is not approved anywhere, carries opioid-class risks, and is mainly known as a racehorse doping agent.
At a Glance
Classification: Naturally occurring amphibian heptapeptide containing a D-amino acid; potent, selective mu-opioid receptor agonist
Dermorphin is a seven-amino-acid opioid peptide first isolated from the skin of the South American frog Phyllomedusa sauvagei. Its sequence is Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2. It is unusual because it contains a D-amino acid (D-alanine), which is rare in animal peptides and helps protect it from breakdown. In early pharmacology work it was many times more potent than morphine on isolated tissues, and hundreds to thousands of times more potent than morphine for pain relief when injected into rat brain ventricles. Dermorphin is not an approved drug anywhere. It is best known outside the lab as a doping agent found in racehorses, and doping-control labs have developed tests for it in both horses and humans. As a mu-opioid agonist, it carries opioid-class risks such as tolerance, dependence and breathing suppression.
What Is Dermorphin?
Dermorphin belongs to a family of frog-skin opioid peptides that also includes the deltorphins (which prefer delta-opioid receptors). The frog gene actually codes for ordinary L-alanine at position 2. An enzyme converts it to D-alanine after the peptide is made, a rare post-translational step. The N-terminal tetrapeptide (Tyr-D-Ala-Phe-Gly) carries the core opioid activity, and the D-Ala2 residue is essential.
What Are Researchers Studying?
Opioid pharmacology and analgesia
Dermorphin produced potent, long-lasting analgesia in mice (IV) and rats (into the brain ventricles). Morphine was 752 to 2,170 times less potent in the rat tests. Naloxone blocked its effects.
Tolerance and dependence
Continuous infusion into rat brain produced tolerance and naloxone-precipitated withdrawal, although less than with morphine in that study. Lower dependence in one rodent study does not mean it is safe or non-addictive.
Peptide biochemistry
Dermorphin is a classic example of a D-amino acid created by post-translational modification of an L-amino acid, studied through cloning of its frog-skin precursor.
Doping and detection
Dermorphin has been found in post-race horse samples. In horses given dermorphin, it caused excitation and increased heart rate after IV dosing, with a plasma half-life under an hour, and was detectable in urine for 48-72 hours. Methods to detect dermorphin in human urine have also been developed for doping control.
Analog development
Most current research uses dermorphin as a template for new mu-opioid analogs (for example, peripherally acting or hybrid peptides), rather than studying dermorphin itself as a therapy.
How Does It Work?
Dermorphin ↓ mu-opioid receptor (MOR), with high selectivity ↓ Gi/o protein signaling: less cAMP, reduced neuronal excitability and neurotransmitter release ↓ analgesia, sedation/catalepsy at high doses, and the usual opioid adverse-effect profile ↓ effects reversed by naloxone.
What Does the Research Show?
Human research
NONE meaningful in PubMed. No controlled human efficacy or safety trials were identified. Human-related publications concern doping detection, not therapy.
Animal research
MODERATE: classic rodent pharmacology and equine pharmacokinetic studies.
In-vitro research
MODERATE: isolated-tissue (guinea-pig ileum, mouse vas deferens) and receptor studies establish mu-opioid activity.
Notable Studies
Amino acid composition and sequence of dermorphin, a novel opiate-like peptide from the skin of Phyllomedusa sauvagei
in-vitroJournal: International Journal of Peptide and Protein Research. Isolation and sequencing of dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) from frog skin, identifying a vertebrate peptide that contains a D-amino acid.
Limitations: Structural identification study; no clinical information.
View publication →Pharmacological data on dermorphins, a new class of potent opioid peptides from amphibian skin
animalJournal: British Journal of Pharmacology. Dermorphin was about 39-40 times more potent than morphine in isolated-tissue assays and produced potent, long-lasting, naloxone-reversible analgesia in mice and rats; morphine was 752-2,170 times less potent after intracerebroventricular injection. Infusion produced tolerance and dependence, less marked than with morphine. The N-terminal tetrapeptide and D-Ala2 were essential.
Limitations: 1981 rodent and isolated-tissue pharmacology; central injection routes; no human data.
View publication →D-alanine in the frog skin peptide dermorphin is derived from L-alanine in the precursor
in-vitroJournal: Science. Cloning of frog-skin dermorphin precursors showed an ordinary alanine codon where D-alanine appears in the final peptide, indicating a novel post-translational L-to-D conversion.
Limitations: Molecular biology study; no pharmacology or clinical data.
View publication →Pharmacokinetics and pharmacodynamics of dermorphin in the horse
animalJournal: Journal of Veterinary Pharmacology and Therapeutics. Ten horses received dermorphin IV and/or IM. Elimination half-life was about 0.7-0.8 hours; IM bioavailability was variable (47-100%). IV dosing caused excitation and increased heart rate for about 5 minutes. Dermorphin was detected in plasma for 12 hours and urine for 48-72 hours.
Limitations: Small equine study focused on doping detection; no therapeutic endpoints.
View publication →What We Still Don't Know
• Human safety, pharmacokinetics and abuse liability (no controlled human studies identified) • Respiratory-depression risk relative to other opioids in people • How much crosses the blood-brain barrier after peripheral injection in humans • Quality and identity of research-market material • Any legitimate therapeutic role for dermorphin itself, as opposed to its analogs
Recent publications
Latest titles from PubMed, not reviewed by Aminodex. Not an endorsement. See all on PubMed ↗
Take the Dermorphin research with you.
Get the Aminodex Dermorphin Brief—a concise summary of the research, notable studies, evidence types, limitations, and references.
One-time email. We do not add you to any mailing list.
Sources & References
- Montecucchi PC et al. Amino acid composition and sequence of dermorphin, a novel opiate-like peptide from the skin of Phyllomedusa sauvagei. International Journal of Peptide and Protein Research. 1981.
- Broccardo M et al. Pharmacological data on dermorphins, a new class of potent opioid peptides from amphibian skin. British Journal of Pharmacology. 1981.
- Richter K et al. D-alanine in the frog skin peptide dermorphin is derived from L-alanine in the precursor. Science. 1987.
- Robinson MA et al. Pharmacokinetics and pharmacodynamics of dermorphin in the horse. Journal of Veterinary Pharmacology and Therapeutics. 2015.
- Castro JL, et al. A high throughput approach for determination of dermorphin in human urine using liquid chromatography-mass spectrometry for doping control purposes. J Mass Spectrom. 2020.
Supplier Listings
A directory of relevant research suppliers for this compound is not yet available.