Melanotan II

Overview

Melanotan II (MT-II) is a cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH) — Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 — developed at the University of Arizona in the 1980s by Hruby, Hadley, and colleagues as a candidate photoprotection / sunless-tanning agent. It has never been approved by the FDA or any other regulator for any indication; clinical development was abandoned and it is sold only via grey-market research-chemical channels. Genuine safety signals have been reported, including darkening of existing moles, eruptive atypical nevi, and case reports of new primary melanoma in young tanning-seeking users.

Mechanism of Action

MT-II is a non-selective agonist at all four peripheral melanocortin receptors — MC1R (melanocyte pigmentation), MC3R and MC4R (energy balance and central sexual arousal), and MC5R (exocrine gland function). MC1R activation on melanocytes increases cAMP → PKA → MITF → tyrosinase, driving eumelanin synthesis; UV exposure is generally required to produce visible tanning. MC4R activation in the hypothalamus mediates the prominent sexual arousal and spontaneous erection side effects seen in the original Phase I trials — this observation was the basis for developing the selective C-terminal analog bremelanotide (PT-141, Vyleesi) for female HSDD.

Research Summary

The seminal Phase I work is Dorr et al. (Life Sciences, 1996; PMID 8637402), a pilot study in three healthy male volunteers that documented dose-dependent facial/buttock pigmentation alongside nausea, yawning/stretching, and spontaneous penile erections. MT-II never progressed to Phase III and was abandoned as a drug candidate, although the structurally related linear afamelanotide (Melanotan-I / Scenesse) was later approved for erythropoietic protoporphyria. As unregulated consumer use expanded, dermatology case reports documented harms: Langan et al. (BMJ, 2009; PMID 19174439) reported mole changes in young users, Cardones & Grichnik (Arch Dermatol, 2009; PMID 19380666) described α-MSH-induced eruptive atypical nevi, and Evans-Brown et al. (BMJ, 2009; PMID 19224885) catalogued population-level unregulated use. Additional case series describe new primary melanoma in young MT-II users and rare rhabdomyolysis. This is not a recommended compound — there is no approved indication, no quality-controlled product, and documented oncologic safety signals.

Dosing Information

Reported Side Effects

• Nausea (very common, especially during loading)
• Facial flushing and transient hypertension
• Spontaneous penile erections / yawning-stretching complex (MC4R-mediated)
• Darkening of existing moles and freckles
• Eruption of new atypical nevi (case reports)
• New primary cutaneous melanoma (case reports in young tanning-seeking users)
• Rhabdomyolysis (rare case reports)
• Appetite suppression
• Fatigue, dizziness, headache
• Injection-site reactions

Research References

• Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study (Dorr et al., Life Sci) (1996)
• Change in moles linked to use of unlicensed 'sun tan jab' (Langan et al., BMJ) (2009)
• alpha-Melanocyte-stimulating hormone-induced eruptive nevi (Cardones & Grichnik, Arch Dermatol) (2009)
• Use of melanotan I and II in the general population (Evans-Brown et al., BMJ) (2009)