Both are α-MSH analogs studied for pigmentation, but they differ in receptor selectivity — and that difference explains Melanotan II’s notorious side-effect profile.
Research reference only. Not medical advice, prescribing guidance, or a product recommendation.
| Dimension | Melanotan II | Melanotan I (Afamelanotide) |
|---|---|---|
| Structure | 7-aa cyclic truncated analog | 13-aa linear α-MSH analog |
| Receptor profile | Non-selective: MC1R / MC3R / MC4R / MC5R | MC1R-selective (~1000× lower MC3R/MC4R) |
| Primary effect | Pigmentation + MC4R central effects | Pigmentation via MC1R |
| Notable side effects | Nausea, flushing, spontaneous erections (MC4R) | Fewer off-target effects |
| FDA status | Not approved | Approved (Scenesse) for EPP photoprotection |
| Characterizing work | Dorr et al., 1996 (Phase I) | Afamelanotide / Scenesse program |
Both peptides activate Gs-coupled melanocortin receptors, raising cAMP to drive melanin production. Afamelanotide (Melanotan I) is a 13-amino-acid analog highly selective for MC1R — roughly 1000-fold lower affinity for MC3R / MC4R — so its action stays largely confined to pigmentation. It is FDA-approved as Scenesse for photoprotection in erythropoietic protoporphyria.
Melanotan II is a truncated 7-amino-acid cyclic analog with much less selectivity, also hitting MC4R centrally. In a 1996 Phase I study (Dorr et al.) it produced tanning alongside dose-dependent nausea, flushing, and spontaneous erections — effects consistent with MC4R activation. Those off-target effects are why MT-II never reached approval: they can’t be cleanly separated from the tan.
The two are a textbook case of selectivity determining safety. Afamelanotide’s MC1R selectivity gives it a clean enough profile to be an approved drug; Melanotan II’s non-selectivity drives both its broader effects and its side effects, and it remains unapproved. This page is a research and educational reference, not a usage recommendation.
Melanotan I (afamelanotide) is a 13-amino-acid analog highly selective for the MC1R receptor and is FDA-approved as Scenesse. Melanotan II is a truncated cyclic analog that activates MC1R, MC3R, MC4R and MC5R non-selectively; its MC4R activity drives side effects, and it is not approved.
Because it is non-selective and activates MC4R in the brain, producing nausea, flushing and spontaneous erections (documented in Dorr et al., 1996) that cannot be cleanly separated from its pigmentation effect.
Afamelanotide (Melanotan I) is FDA-approved as Scenesse for photoprotection in erythropoietic protoporphyria. Melanotan II is not FDA-approved. This page is a research and educational reference.
Both stimulate melanin production through MC1R. Melanotan I does so selectively; Melanotan II does so along with broader, non-selective melanocortin effects.