Identity a synthetic cyclic heptapeptide (7 amino acids), sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ — a non-selective melanocortin agonist (activates MC1R, MC3R, MC4R and MC5R), up to ~1000× more potent than natural α-MSH at stimulating melanin, and able to cross the blood-brain barrier (hence the central effects). ## Development & history - Groundwork: 1960s research showed α-MSH triggered sexual arousal in rats; interest carried into the 1980s.
- At the University of Arizona (1980s–early 1990s), Mac E. Hadley and Victor J. Hruby set out to build α-MSH analogs as sunless-tanning / skin-cancer-chemoprevention agents — the idea being a protective tan without UV. They synthesised Melanotan-I and Melanotan II.
- The pivotal accident: while self-experimenting with Melanotan II, one of the scientists injected ~twice the intended dose and got an ~eight-hour erection, plus nausea and vomiting — revealing that MT-II acts centrally (MC4R) as well as on skin (MC1R). A 1996 pilot (Dorr et al., Life Sciences, 3 volunteers) then documented dose-dependent tanning alongside nausea, flushing and spontaneous erections.
- Australian-government-funded human trials followed (Hadley, late 1990s), but the side-effect burden showed it was impractical as a drug, and it was never approved. The erection finding was spun off into PT-141 / bremelanotide (#46) — which was eventually FDA-approved. MT-II itself went gray-market, sold online and in tanning salons and gyms from the mid-2000s. ## Mechanism (as proposed) a non-selective melanocortin agonist — MC1R on skin melanocytes → melanin synthesis (tanning); MC4R in the hypothalamus → sexual arousal/erection and appetite suppression; plus MC3R/MC5R. Because it crosses the blood-brain barrier, the central (MC4R) effects accompany the skin (MC1R) effect — which is exactly why a "tanning" compound also causes erections, nausea and other systemic effects.