Effect of MELANOTAN®, [Nle4, D-Phe7]-α-MSH, on melanin synthesis in humans with MC1R variant alleles

MELANOTAN® (NDP-MSH) binds the MC1 receptor to significantly increase the eumelanin content of human skin cells. In this study of 77 Caucasian individuals, we investigated the effects of MELANOTAN® in individuals with variant MC1R genotypes, as it has been suggested through in vitro studies that variant alleles decrease MELANOTAN® binding efficacy, which would subsequently affect the synthesis of melanin. Administration of MELANOTAN® produced a significant (p < 0.001) increase in melanin density in treated, compared to placebo, individuals. Importantly, MELANOTAN® increased the melanin density to a greater extent in individuals carrying the variant alleles Val60Leu, Asp84Glu, Val92Met, Arg142His, Arg151Cys, and Arg160Trp than in individuals with no variant alleles. This study demonstrates that MELANOTAN® effectively increases the melanin content of skin in those individuals with MC1R variant alleles and therefore, those most in need of photoprotection.