Dermorphin vs Apraglutide
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, Frog juice
Dermorphin is a seven-amino-acid opioid peptide (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) first found in the skin of South American Phyllomedusa frogs. It is a strong, highly selective mu-opioid agonist, the same receptor morphine and fentanyl hit, and in mouse brain-injection studies it was hundreds of times more potent than morphine. It is not approved anywhere for human use. Its main claim to fame is doping: it was caught in dozens of American racehorses in 2012, where it was nicknamed 'frog juice'. This is an opioid, and it should be treated like one.
Also: FE 203799, Once-weekly GLP-2 analog
Apraglutide is a once-weekly GLP-2 analog for short bowel syndrome, originally from VectivBio and now owned by Ironwood Pharmaceuticals. Its phase 3 STARS trial hit its main goal in 2024, but in April 2025 Ironwood said the FDA wanted a confirmatory trial, partly because patients in STARS got less drug exposure than planned due to how doses were prepared and given. That new trial, STARS-2, started in June 2026, so approval is years away (a submission before end of 2029 has been mentioned).
Key Comparison Insights
- Both peptides belong to the Healing category, suggesting similar primary applications.
- Apraglutide has stronger research evidence (Human Trials) compared to Dermorphin (Animal Studies).
Detailed Comparison
| Attribute | Dermorphin | Apraglutide |
|---|---|---|
| Category | Healing | Healing |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | Dermorphin binds the mu-opioid receptor with very high affinity and selectivity. In rat brain binding work it had a Ki of 0.7 nM at mu receptors versus 62 nM at delta and over 5,000 nM at kappa receptors, a selectivity on par with the reference lab mu-agonist DAMGO. It is unusual for a natural peptide because its second amino acid is a D-alanine, which protects it from the enzymes that normally chew up opioid peptides within seconds. Mu activation blocks pain signaling in the spinal cord and brain, and it also drives the classic opioid problems: euphoria, sedation, slowed breathing, constipation, tolerance and dependence. There is no special 'safe' mechanism here. Claims that it is less addictive than morphine are mostly marketing and horse-racing talk, not proven in people. | Like teduglutide and glepaglutide, apraglutide activates GLP-2 receptors in the gut, signaling the intestinal lining to grow and absorb more. It was engineered for very low clearance and high plasma protein binding, which gives it a much longer half-life. In rat studies its IV half-life was about 159 minutes versus 19 for teduglutide and 16 for glepaglutide, and it kept more gut-growth activity when dosed less often. That is the basis for once-weekly dosing in humans. Same class caveat as the others: long-term stimulation of gut tissue growth carries a theoretical polyp and tumor risk that requires monitoring. |
| Common Dosing | No safe human dose established Not established | 2.5-5 mg once weekly by body weight (trial dose) Once weekly |
| Administration | Intravenous infusion (human study); intravenous or intramuscular (horse study) | Subcutaneous injection once weekly |
| Typical Duration | Single administrations in research settings | 24-week primary endpoint, with treatment continued to week 48 and beyond in STARS |
| Best Time to Take | Not applicable | Same day each week (trial schedule) |
Possible Side Effects May vary by individual |
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| Research Summary | Most of the science is animal pharmacology and drug-testing chemistry. A 1990 rat-brain study confirmed dermorphin as a near-specific mu 'super-agonist' and found that, injected into the brains of mice, it was up to 670 times more potent than morphine as a painkiller, with higher doses causing catalepsy. The human data are tiny: a 1986 Brain Research study gave an intravenous infusion of 0.16 mg/kg to healthy volunteers and found a marked, long-lasting rise in the threshold of a spinal pain reflex; naloxone only reversed about half the effect. No modern clinical trials exist. In horses, a 2015 pharmacokinetic study (about 9 mcg/kg IV or IM) found an elimination half-life under an hour, excitation with a raised heart rate after IV dosing, and detection in urine for 48 to 72 hours. The doping story is the reason most people have heard of it: around 30 positive tests turned up in Southern US racing in 2012, including 11 horses tied to nine trainers in Louisiana, which led to suspensions of up to 10 years, and racing labs in Australia, the US and Hong Kong have since built sensitive tests for dermorphin and its synthetic analogs. A 2017 federal indictment charged a Louisiana veterinarian with supplying it to trainers. | STARS (NCT04627025) randomized 164 adults with SBS and intestinal failure 2:1 to weekly apraglutide (2.5 mg or 5 mg by body weight) or placebo. Topline results in February 2024: weekly parenteral support volume fell 25.5% versus 12.5% on placebo at week 24 (p=0.001). In stoma patients the gap was bigger (25.6% vs 7.8%), and 43% vs 27.5% gained at least one day a week off IV support. But the colon-in-continuity endpoints missed, and enteral autonomy at week 48 (12.5% vs 7.4%) was not significant. Discontinuation for side effects was low (3.6% vs 1.9%). While preparing the NDA, Ironwood found exposure in STARS was lower than intended because of dose preparation and administration, and in April 2025 said the FDA required a confirmatory trial. STARS-2 is a 24-week, placebo-controlled trial of about 124 patients (NCT07742735), started June 2026. So: a positive phase 3 on paper, with a dosing problem that undercuts confidence, and no approval in sight before the end of the decade. |
Frequently Asked Questions: Dermorphin vs Apraglutide
What is the difference between Dermorphin and Apraglutide?
Dermorphin is a healing peptide that dermorphin is a seven-amino-acid opioid peptide (tyr-d-ala-phe-gly-tyr-pro-ser-nh2) first found in the skin of south american phyllomedusa frogs. it is a strong, highly selective mu-opioid agonist, the same receptor morphine and fentanyl hit, and in mouse brain-injection studies it was hundreds of times more potent than morphine. it is not approved anywhere for human use. its main claim to fame is doping: it was caught in dozens of american racehorses in 2012, where it was nicknamed 'frog juice'. this is an opioid, and it should be treated like one. Apraglutide is a healing peptide that apraglutide is a once-weekly glp-2 analog for short bowel syndrome, originally from vectivbio and now owned by ironwood pharmaceuticals. its phase 3 stars trial hit its main goal in 2024, but in april 2025 ironwood said the fda wanted a confirmatory trial, partly because patients in stars got less drug exposure than planned due to how doses were prepared and given. that new trial, stars-2, started in june 2026, so approval is years away (a submission before end of 2029 has been mentioned). The main differences lie in their mechanisms of action and clinical applications.
Which is better, Dermorphin or Apraglutide?
Neither is universally "better" - the choice depends on your specific goals. Dermorphin is typically used for healing purposes, while Apraglutide is used for healing. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can Dermorphin and Apraglutide be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Dermorphin and Apraglutide together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.