Melanotan I (Afamelanotide) Mechanism of Action
How Melanotan I (Afamelanotide) works: receptor targets, signalling pathways, and molecular profile.
Selective MC1R Activation
Melanotan I (afamelanotide) activates only the MC1R (melanocortin-1 receptor), the pigment-specific receptor that drives melanin production in skin. This is the key structural/functional difference from Melanotan II, which activates MC1R alongside MC3R and MC4R — receptors responsible for appetite and sexual-arousal effects. By targeting MC1R alone, afamelanotide produces skin darkening and photoprotection without those broader systemic effects.
Photoprotection Mechanism
Increased melanin production provides genuine photoprotective benefit by absorbing and dissipating UV and visible-light energy before it damages skin cells — the basis for its approved use in erythropoietic protoporphyria (EPP), where accumulated porphyrins make even normal light exposure intensely painful.
References
- Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo · Lim HW, et al. · 2015