One Receptor System, Many Effects

The melanocortin system comprises five receptor subtypes (MC1–MC5) that, depending on their distribution in the body, control entirely different processes – from skin pigmentation to appetite to sexual function.

Selectivity Makes the Difference

Melanotan I is largely selective for the MC1 receptor on melanocytes and is therefore primarily associated with pigmentation effects. The corresponding drug class (afamelanotide) has been approved since 2019 under the name Scenesse for a rare light-sensitivity disorder – one of the few melanocortin peptides with formal FDA approval.

Melanotan II, by contrast, activates several receptors at once (MC1, MC3, MC4, MC5), resulting in a broader but less predictable effect profile spanning pigmentation, appetite, and sexual function simultaneously.

PT-141 (bremelanotide), originally derived from Melanotan II research, was specifically focused on the MC4 receptor in the hypothalamus. It has been approved since 2019 as Vyleesi for treating HSDD in premenopausal women.

Sources

  • Langendonk JG, et al. NEJM. 2015;373(1):48–59. PMID 26132941
  • Dorr RT, et al. Life Sciences. 1996;58(20):1777–1784. PMID 8637402
  • Clayton AH, et al. Obstet Gynecol. 2019;134(5):899–908. PMID 31599840

References without a PMID can be located via the respective publisher.