Melanotan I
A synthetic version of a hormone that triggers skin darkening. It selectively activates the receptors that produce protective dark pigment (eumelanin) and UV protection. Approved for a rare condition where sun exposure causes severe pain. More selective than Melanotan II — produces skin tanning without the sexual arousal or appetite suppression. People use it for tanning and sun protection.
Dosage
0.5-1 mg subcutaneous daily (loading) then reduced frequency
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
0.5 hours (melanin production effects persist for weeks after dosing)
Half-Life Calculator →Administration
Subcutaneous implant (approved) or subcutaneous injection (research)
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Effects
Skin Tanning
Selective MC1R activation drives eumelanin production for genuine UV protection.
UV Protection
Eumelanin absorbs UV radiation and scavenges free radicals — FDA-approved for EPP.
Mechanism of Action
Melanotan I (afamelanotide) is a linear 13-amino-acid analogue of alpha-melanocyte stimulating hormone (α-MSH) with a single amino acid substitution (norleucine for methionine at position 4) that confers enhanced potency and metabolic stability. It acts as a selective agonist of the melanocortin 1 receptor (MC1R), the primary melanocortin receptor expressed on epidermal melanocytes.
MC1R is a Gs-coupled GPCR that, upon activation, stimulates adenylyl cyclase to produce cAMP. Elevated cAMP activates protein kinase A (PKA), which phosphorylates the CREB transcription factor. Phospho-CREB translocates to the nucleus and activates transcription of microphthalmia-associated transcription factor (MITF) — the master regulator of melanocyte biology. MITF drives expression of the key melanogenic enzymes: tyrosinase (the rate-limiting enzyme that converts tyrosine to DOPA and then to dopaquinone), tyrosinase-related protein 1 (TRP-1), and dopachrome tautomerase (TRP-2). These enzymes collectively convert dopaquinone through a series of oxidation and polymerization steps into eumelanin, the brown-black photoprotective pigment.
The selectivity of Melanotan I for MC1R over MC3R, MC4R, and MC5R is what distinguishes it from Melanotan II. MC4R activation in the hypothalamus drives sexual arousal and appetite suppression — effects that MT-I largely avoids. The eumelanin produced by MC1R stimulation provides genuine photoprotection by absorbing UV radiation and scavenging free radicals generated by UV exposure. This is why afamelanotide received FDA approval for erythropoietic protoporphyria (EPP) — patients with this condition have extreme photosensitivity, and the increased eumelanin provides a UV-absorbing shield that significantly extends their pain-free sun exposure time.
Regulatory Status
FDA approved (2019) as Scenesse for erythropoietic protoporphyria (EPP). EMA approved (2014). Off-label tanning use through research suppliers.
Risks & Safety
Common
nausea, facial flushing, headache, injection site reactions, darkening of existing moles and freckles.
Serious
may hide warning signs of skin cancer because overall skin darkening can mask changes; mole changes require dermatologist monitoring.
Rare
severe nausea, hypersensitivity reactions. Fewer sexual and appetite side effects than Melanotan II.
Compare Melanotan I With
Research Papers
8Published: January 4, 2026
AI Summary
Skin pigmentation by the endogenous pigment melanin is a highly coordinated process in which hormones play a crucial role. They are synthesized not only in classical endocrine organs but also in the skin itself, which acts as an independent endocrine organ. Among the endocrine target structures of the skin, the melanocortin 1 receptor (MC1R) is of particular importance.
Published: September 9, 2024
AI Summary
Glioblastoma is the most aggressive form of brain tumor and has a dismal prognosis; therefore, novel therapeutic approaches based on the mechanisms underlying its aggressive nature are urgently required. A growing body of evidence suggests that neurotransmitters play a key role in modulating the biology of glioblastoma; however, the role of melanocortins remains unclear..
Published: September 30, 2024
AI Summary
Postnatal hippocampal neurogenesis is essential for learning and memory. Hippocampal neural precursor cells (NPCs) can be induced to proliferate and differentiate into either glial cells or dentate granule cells. Notably, hippocampal neurogenesis decreases dramatically with age, partly due to a reduction in the NPC pool and a decrease in their proliferative activity.
Published: July 31, 2024
AI Summary
This study aimed to develop polysorbate 80-coated chitosan nanoparticles (PS80/CS NPs) as a delivery system for improved brain targeting of α-Melanocyte Stimulating Hormone analog (NDP-MSH). Chitosan nanoparticles loaded with NDP-MSH were surface-modified with polysorbate 80 ([NDP-MSH]-PS80/CS NP), which formed a flattened layer on their surface. Nanoparticle preparation involved ionic gelation...
Published: January 2, 2023
AI Summary
Voluntary feed intake is insufficient to meet the nutrient demands associated with late pregnancy in prolific ewes and early lactation in high-yielding dairy cows. Under these conditions, peripheral signals such as growth hormone and ceramides trigger adaptations aimed at preserving metabolic well-being. Recent work in rodents has shown that the central nervous system-melanocortin (CNS-MC) syst...
Published: January 9, 2022
AI Summary
Alzheimer's disease (AD) is the most frequent cause of dementia and still lacks effective therapy. Clinical signs of AD include low levels of endogenous melanocortins (MCs) and previous studies have shown that treatment with MC analogs induces neuroprotection in the early stages of AD..
Published: November 23, 2021
AI Summary
The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy homeostasis and appetite, is a class A G-protein-coupled receptor and a prime target for the pharmacological treatment of obesity. Here, we present cryo-electron microscopy structures of MC4R-Gs-protein complexes with two drugs recently approved by the FDA, the peptide agonists NDP-α-MSH and setmelanotide, with 2...
Published: July 14, 2021
AI Summary
The increasing use of marginal lungs for transplantation encourages novel approaches to improve graft quality. Melanocortins and their receptors (MCRs) exert multiple beneficial effects in pulmonary inflammation. We tested the idea that treatment with the synthetic α-melanocyte-stimulating hormone analogue [Nle4,D-Phe7]-α-MSH (NDP-MSH) during ex vivo lung perfusion (EVLP) could exert positive i...
Frequently Asked Questions
What is Melanotan I?
A synthetic version of a hormone that triggers skin darkening. It selectively activates the receptors that produce protective dark pigment (eumelanin) and UV protection. Approved for a rare condition where sun exposure causes severe pain. More selective than Melanotan II — produces skin tanning without the sexual arousal or appetite suppression. People use it for tanning and sun protection.
What is Melanotan I used for?
A synthetic version of a hormone that triggers skin darkening. It selectively activates the receptors that produce protective dark pigment (eumelanin) and UV protection. Approved for a rare condition where sun exposure causes severe pain. More selective than Melanotan II — produces skin tanning without the sexual arousal or appetite suppression. People use it for tanning and sun protection.
What is the dosage for Melanotan I?
FDA-approved (Scenesse): 16 mg subcutaneous implant every 2 months. Research/off-label: 0.5-1 mg subcutaneous once daily during loading phase, then reduced frequency for maintenance.
What are the side effects of Melanotan I?
Common: nausea, facial flushing, headache, injection site reactions, darkening of existing moles and freckles. Serious: may hide warning signs of skin cancer because overall skin darkening can mask changes; mole changes require dermatologist monitoring. Rare: severe nausea, hypersensitivity reactions. Fewer sexual and appetite side effects than Melanotan II.
How does Melanotan I work?
Melanotan I (afamelanotide) is a linear 13-amino-acid analogue of alpha-melanocyte stimulating hormone (α-MSH) with a single amino acid substitution (norleucine for methionine at position 4) that confers enhanced potency and metabolic stability. It acts as a selective agonist of the melanocortin 1 receptor (MC1R), the primary melanocortin receptor expressed on epidermal melanocytes. MC1R is a Gs-coupled GPCR that, upon activation, stimulates adenylyl cyclase to produce cAMP. Elevated cAMP activates protein kinase A (PKA), which phosphorylates the CREB transcription factor. Phospho-CREB translocates to the nucleus and activates transcription of microphthalmia-associated transcription factor (MITF) — the master regulator of melanocyte biology. MITF drives expression of the key melanogenic enzymes: tyrosinase (the rate-limiting enzyme that converts tyrosine to DOPA and then to dopaquinone), tyrosinase-related protein 1 (TRP-1), and dopachrome tautomerase (TRP-2). These enzymes collectively convert dopaquinone through a series of oxidation and polymerization steps into eumelanin, the brown-black photoprotective pigment. The selectivity of Melanotan I for MC1R over MC3R, MC4R, and MC5R is what distinguishes it from Melanotan II. MC4R activation in the hypothalamus drives sexual arousal and appetite suppression — effects that MT-I largely avoids. The eumelanin produced by MC1R stimulation provides genuine photoprotection by absorbing UV radiation and scavenging free radicals generated by UV exposure. This is why afamelanotide received FDA approval for erythropoietic protoporphyria (EPP) — patients with this condition have extreme photosensitivity, and the increased eumelanin provides a UV-absorbing shield that significantly extends their pain-free sun exposure time.
How is Melanotan I administered?
Melanotan I is administered via subcutaneous implant (approved) or subcutaneous injection (research).
What is the half-life of Melanotan I?
The half-life of Melanotan I is 0.5 hours (melanin production effects persist for weeks after dosing).
Is Melanotan I legal?
FDA approved (2019) as Scenesse for erythropoietic protoporphyria (EPP). EMA approved (2014). Off-label tanning use through research suppliers.
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