Identity a synthetic cyclic heptapeptide (7 amino acids, cyclically constrained for stability), a melanocortin-receptor agonist — strongest at MC4R, with some MC1R/MC3R activity. It is a metabolite/derivative of Melanotan II, engineered to be more MC4R-selective (sexual effect) and less MC1R (tanning). ## Development & history - In the 1980s at the University of Arizona, Mac E. Hadley and Victor J. Hruby were developing α-MSH analogs as sunless-tanning agents (to induce protective melanin without UV), synthesising Melanotan-I and Melanotan II.
- The discovery: while self-experimenting with Melanotan II, one of the scientists accidentally injected roughly twice the intended dose and experienced an ~eight-hour erection, along with nausea and vomiting. That unexpected central effect (later documented in a 1996 pilot trial and a 1998 placebo-controlled crossover study, Wessells et al., J Urology — erections in 8 of 10 men) redirected an entire research line from tanning toward sexual function. Hadley published it as "Discovery that a melanocortin regulates sexual functions in male and female humans" (Peptides, 2005).
- Palatin Technologies developed bremelanotide (PT-141) from Melanotan II for sexual dysfunction. An intranasal formulation was trialed for erectile dysfunction (Phase 2b; 2007 BJU Int: ~60% of men with mild-moderate ED responded vs 27% placebo) — but the ED program was abandoned because of blood-pressure increases (and PDE5-inhibitor competition).
- Palatin pivoted to a subcutaneous formulation for HSDD in premenopausal women (no approved drug existed then bar flibanserin). Two Phase 3 RECONNECT trials led to FDA approval of Vyleesi in June 2019 — one of only two FDA-approved drugs for female sexual dysfunction. ## Mechanism (as proposed) a central melanocortin agonist — activates MC4R (and MC3R) in the hypothalamus (paraventricular nucleus, medial preoptic area), driving sexual desire and arousal through dopaminergic and oxytocin pathways and autonomic output to the pelvis. This is fundamentally different from PDE5 inhibitors (sildenafil), which act peripherally on blood flow — PT-141 is better described as a desire enhancer than a blood-flow one, and its effect does not depend on hormone levels or direct stimulation.