Melanotan II: Non-Selective Melanocortin Agonist

Synthetic cyclic analogue of α-MSH developed as a UV-free tanning agent and precursor to PT-141. Never approved; widely sold illicitly.

👥 Human studies

Full name
Melanotan II (MT-II)
Class
Non-selective MC1R/MC3R/MC4R agonist (cyclic heptapeptide)
Half-life
~1 hour
Route
Subcutaneous (illicit); also intranasal
Developer
University of Arizona (academic) → partial clinical programmes
Regulatory status
No approval anywhere; multiple national health warnings

What it is

Melanotan II was developed at the University of Arizona in the 1980s as a potential UV-free tanning agent. Because it is a non-selective melanocortin agonist, it activates MC1R (pigmentation), MC3R/MC4R (appetite, arousal), with off-target effects. PT-141 is a selective derivative.

How it works

MC1R agonism on melanocytes stimulates eumelanin production, producing tanning even without UV exposure. Effects persist for weeks after dosing stops.

MC3R/MC4R activation in the central nervous system causes nausea, reduced appetite, spontaneous erections in men, and flushing — off-target effects that limit tolerability and contributed to its non-approval.

What the research shows

Academic pharmacodynamic studies and multiple case reports of illicit use.

Dorr RT et al. (1996) — Phase 1/2 in healthy volunteers

Dorr R.T. et al., Life Sci 1996;58:1777–1784. 👥 Human studies

Healthy volunteers received subcutaneous MT-II with concomitant UV.

Melanin density increased and tanning was achieved with lower UV doses; nausea and flushing were dose-limiting.

Limitations: Off-target effects substantial; programme not continued commercially.

Langan EA et al. (2010) — case-series and atypical naevi

Langan E.A. et al., BMJ 2009;338:b577 (case series). 👥 Human studies

Multiple case reports of new or changing naevi, atypical dysplastic lesions, and rare melanoma in users of illicit MT-II.

Dermatology bodies in the UK, Australia and Europe have issued public warnings.

Limitations: Causality not definitively established; case-based evidence.

Safety and limitations

Common: nausea (severe with initial doses), spontaneous erections, flushing, darkening of moles, focal hyperpigmentation, and lip/gingival darkening. Rare: reports of rhabdomyolysis, kidney injury, and changing naevi.

Illicit preparations sold online have unpredictable purity. Multiple national drug agencies have issued warnings.

Sources

  1. Dorr R.T. et al. Life Sci 1996;58:1777–1784. PubMed
  2. Langan E.A. et al. BMJ 2009;338:b577. PubMed

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