Melanotan I
Afamelanotide / Scenesse / MT-1 / NDP-alpha-MSH
Melanotan I (afamelanotide) is a synthetic 13-amino acid linear analog of alpha-melanocyte stimulating hormone (alpha-MSH) that selectively agonizes the melanocortin-1 receptor (MC1R) to stimulate eumelanin production in the skin. It is FDA-approved under the brand name Scenesse as a subcutaneous implant for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). Unlike its counterpart Melanotan II, afamelanotide has a more selective receptor profile with significantly fewer systemic side effects.
Mechanism of Action
Synthetic analog of alpha-melanocyte stimulating hormone (alpha-MSH). Binds melanocortin-1 receptor (MC1R) on melanocytes, stimulating eumelanin production and distribution. Produces gradual, UV-independent tanning. Does not significantly affect sexual function (unlike MT-II).
Research Protocols
For research purposes only. Not medical advice.
Research protocols use 0.5-1mg daily via subcutaneous injection for 10-14 days as a loading phase, then 0.5mg 2-3 times weekly for maintenance. Some UV exposure enhances tanning response.
Research Notes
Clinical Research Status
Afamelanotide received FDA approval in October 2019 and EMA approval in 2014 for erythropoietic protoporphyria, making it one of the few melanocortin peptides to achieve regulatory approval. Additional clinical trials have investigated its potential in vitiligo (to enhance repigmentation when combined with UV therapy), polymorphous light eruption, and solar urticaria. Research into its photoprotective properties for skin cancer prevention in organ transplant recipients has also been explored in Phase II studies.
Key Published Findings
The pivotal Phase III trial (CUV039) demonstrated that afamelanotide significantly increased pain-free time in sunlight for EPP patients compared to placebo, with a median increase of approximately 70 hours over a 6-month period. Vitiligo studies show enhanced and accelerated repigmentation when afamelanotide implants are combined with narrowband UVB phototherapy compared to phototherapy alone. Mechanistic research confirms that MC1R activation by afamelanotide triggers eumelanin synthesis through the cAMP/PKA pathway without requiring UV exposure.
Safety Profile
The most common adverse effects include nausea, headache, and darkening of pre-existing nevi (moles), with injection site reactions at the implant location. Unlike Melanotan II, afamelanotide does not typically cause facial flushing, nausea at therapeutic doses, or sexual side effects due to its selectivity for MC1R over MC3R/MC4R. Long-term surveillance data spanning over a decade of use has not identified increased melanoma risk, though regular dermatological monitoring is recommended.
Comparison to Related Compounds
Melanotan I is a linear peptide with high MC1R selectivity, while Melanotan II is a cyclic heptapeptide with broad activity across MC1R, MC3R, MC4R, and MC5R receptors, explaining MT-II's wider side effect profile including appetite suppression and sexual effects. Afamelanotide produces more gradual, natural-appearing tanning compared to the rapid but sometimes uneven pigmentation seen with Melanotan II. The FDA-approved implant formulation provides sustained release over approximately 60 days, whereas MT-II requires frequent subcutaneous injections.
Community Observations
Users seeking cosmetic tanning generally prefer Melanotan II for its faster onset and additional effects, while those specifically interested in photoprotection without sexual side effects may prefer Melanotan I. The FDA-approved implant form (Scenesse) is extremely expensive and limited to EPP patients, leading some users to source research-grade afamelanotide powder for self-administration. Community reports suggest more natural and even tanning compared to MT-II, but with a slower onset typically requiring 2-4 weeks before visible pigmentation changes.
Half-Life
~30 minutes
Reconstitution
Bacteriostatic water (BAC)
Storage
Lyophilized
Refrigerate 2-8C up to 24 months. Protect from light.
Reconstituted
Refrigerate 2-8C. Use within 30 days.
US Legal Status
Also Known As
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