Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans with MC1R variant alleles

Peptides. 2006 Feb;27(2):388-94. doi: 10.1016/j.peptides.2004.12.038. Epub 2005 Nov 15.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Alleles*
  • Double-Blind Method
  • Genetic Variation*
  • Humans
  • Melanins / biosynthesis*
  • Protein Binding / genetics
  • Receptor, Melanocortin, Type 1 / drug effects*
  • Receptor, Melanocortin, Type 1 / genetics*
  • Treatment Outcome
  • White People / genetics
  • alpha-MSH / analogs & derivatives*
  • alpha-MSH / pharmacology


  • Melanins
  • Receptor, Melanocortin, Type 1
  • alpha-MSH
  • MSH, 4-Nle-7-Phe-alpha-