Peptide Protocol

Melanotan I: selective MC1R — photoprotective tanning, no side effects.

α-MSH analog with high MC1R selectivity. Induces photoprotective melanogenesis without the sexual side effects of Melanotan II.

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peppercalc.com · research use only
250 mcg–1 mg
Daily SubQ Dose
4–8 weeks on / 8 off
Cycle
SubQ injection
Route
Once daily
Frequency
Overview

What is Melanotan I?

Melanotan I (afamelanotide) was developed at the University of Arizona as a stable, potent analog of α-MSH. The [Nle4,D-Phe7]-α-MSH modification dramatically extends its half-life and receptor affinity. By selectively activating MC1R on melanocytes, it stimulates eumelanin production — the brown/black photoprotective form of melanin — without the broad melanocortin receptor activation of Melanotan II.

Scenesse® (afamelanotide 16 mg implant) received EMA approval in 2014 and FDA approval in 2019 for EPP — a rare genetic condition causing severe phototoxic pain. Beyond this approved indication, Melanotan I is researched for photoprotection in polymorphous light eruption and as a skin-darkening agent. Its selectivity profile makes it significantly safer than Melanotan II for cosmetic melanogenesis research.

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MC1R Agonism
Selectively activates melanocortin 1 receptors on melanocytes, triggering cAMP-mediated upregulation of MITF and melanogenic enzymes (tyrosinase, TRP-1, TRP-2).
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Eumelanin Production
Preferentially stimulates production of eumelanin (brown/black) over phaeomelanin (red/yellow), producing photoprotective pigmentation.
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Photoprotection
UV-independent eumelanin buildup provides intrinsic photoprotective barrier, reducing photosensitivity and UV-induced DNA damage.
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MC4R Sparing
Does not activate MC4R or MC3R, avoiding the sexual arousal (MC4R) and metabolic (MC3R) effects characteristic of Melanotan II.
Dosing Protocol

Dosing Schedule

Parameters documented in published preclinical and clinical research.

⚠️ Research use only. The following documents parameters from published preclinical and clinical research. Not medical advice. Not for human consumption. Consult a licensed healthcare professional before any use.
PhaseDoseFrequencyDurationNotes
FDA-approved implant16 mg implantEvery 60 daysPer EPP protocolScenesse 16 mg biodegradable SubQ implant for EPP only. Physician-administered — not applicable to injection protocol.
Starting dose250 mcgDaily SubQDays 1–5Start low to assess nausea and flushing response before escalating.
Research injection500 mcg–1 mgDaily SubQ2–4 weeksAdvance to 500 mcg after tolerance is established. Injection protocol for melanogenesis research — not FDA-approved.
Maintenance500 mcgEvery other dayOngoingLower-frequency maintenance after initial melanogenesis loading phase.
Off cycle8–12 weeksAllow natural melanin fade between research cycles.
Safety Profile

Safety & Side Effects

✓ Generally Well Tolerated
FDA and EMA approved (Scenesse) for EPP — highest regulatory validation
MC1R-selective — no sexual or appetite side effects
Extensive clinical safety data from EPP trials
Stimulates photoprotective eumelanin specifically
⚠ Potential Concerns
Nausea common, especially with higher injection doses
Spontaneous erections not reported (unlike MT-II) but facial flushing possible
Research-grade injections lack EPP-approved formulation quality control
Theoretical melanoma concern — clinical EPP data does not support but warrants monitoring
⚠️
Research use onlyThis page is an educational reference. None of this constitutes medical advice. Consult a qualified professional before any use. All compounds are for research purposes only.
Evidence Base

Academic References

  1. [1]
    Minder EI, et al. (2009). Afamelanotide, an agonistic analogue of α-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria. Expert Opin Investig Drugs. 18(12):1925–35. PubMed ↗
  2. [2]
    Langendonk JG, et al. (2015). Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 373(1):48–59. PubMed ↗
  3. [3]
    Harms J, et al. (2009). An alpha-melanocyte-stimulating hormone analogue in erythropoietic protoporphyria. Br J Dermatol. 160(2):266–72. PubMed ↗
  4. [4]
    Hadley ME, Dorr RT. (2006). Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 27(4):921–30. PubMed ↗
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