Melanotan I

Both are alpha-MSH analogs, but their real-world profiles diverge. Melanotan II is a cyclic, non-selective melanocortin agonist with strong central activity at MC3R/MC4R, which is why research subjects report libido effects, appetite suppression, and nausea alongside tanning. Melanotan I (afamelanotide) is a linear analog whose effect in practice is dominated by MC1R-driven pigmentation, with far less of that central activity. If the research target is pigmentation with a cleaner side-effect profile, Melanotan I is the analog that went on to become a licensed drug.

Afamelanotide is the pharmaceutical name for Melanotan I ([Nle4-D-Phe7]-alpha-MSH). Marketed as Scenesse by Clinuvel, it is a 16mg controlled-release subcutaneous implant given roughly every two months. The EMA approved it in 2014 and the FDA in 2019, making it the first melanocortin analog to reach approval. Its approved indication is preventing phototoxicity in adults with erythropoietic protoporphyria.

EPP is a rare inherited disorder in which protoporphyrin builds up in the skin and causes severe burning pain within minutes of sunlight or even visible light. In the pivotal randomized, placebo-controlled trials, afamelanotide increased pain-free light exposure and improved quality of life versus placebo [1]. A long-term observational study in 115 patients supported sustained benefit and tolerability [4]. The proposed mechanism is MC1R-driven eumelanin plus enhanced antioxidant and DNA-repair activity [3,5].

Reports and clinical data point to much less. The spontaneous erections, appetite suppression, and nausea linked to Melanotan II are driven largely by central MC3R/MC4R activity. Melanotan I's profile is dominated by MC1R pigmentation, so those central effects are far less prominent at typical doses, though mild facial flushing and transient nausea can still occur.

Not strictly. In receptor-binding assays afamelanotide is a potent agonist across several melanocortin receptors, similar to native alpha-MSH. What separates it from Melanotan II in practice is a pigmentation-dominant, milder central profile rather than pure receptor selectivity [2]. Describing it as flatly 'MC1R-selective' is a simplification worth being honest about.

For research use, a 10mg vial is typically reconstituted with 1mL of bacteriostatic water, giving 10mg/mL (so 500 mcg equals 0.05mL, or 5 units on a U-100 insulin syringe). Community loading protocols use roughly 0.5-1mg subcutaneously daily until target pigmentation, then 2-3x weekly maintenance. The licensed clinical form is instead a 16mg controlled-release implant. Refrigerate after reconstitution and protect from light.