★ Endocrine & Melanocortin

Melanotan II

Endocrine & Melanocortin · 10mg × 10 vials

Non-selective melanocortin agonist. Studied for melanogenesis and central melanocortin signaling.

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Overview

What Is Melanotan II?

Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone. It is a non-selective melanocortin receptor agonist with activity at MC1R, MC3R, MC4R, and MC5R. The pigmentation effect arises from MC1R activation on melanocytes, which upregulates eumelanin synthesis and shifts output away from lighter pheomelanin. UV exposure still triggers tan formation; MT2 increases the gain of the melanocyte response, so pigmentation develops at lower cumulative UV dose in the published studies.

The sexual-arousal effect is driven by MC4R activation in the central nervous system, the same receptor that PT-141 (bremelanotide) targets selectively, and the nausea, flushing, and yawning reported in trials are MC3R and MC4R crossover effects. MT2 was synthesised in the 1980s by Mac Hadley and Victor Hruby at the University of Arizona in a programme searching for a sunless-tanning agent to reduce melanoma risk in fair-skinned populations. It was never developed into an approved drug and its patent expired. PT-141 was derived from MT2 by retaining the sexual-response arm while reducing the pigmentary activity; MT2 is the older, broader-spectrum parent compound.

Published Safety Data

What the published studies measured.

What the studies show

Measured in clinical trials

Nausea: 50-70% in small phase 1 studies (Levine et al, Arizona, 1991) - mostly first-dose, tachyphylaxes within 3-5 doses
Flushing: ~40-50% in early studies - transient, 30-90 minutes post-dose, more pronounced in fair skin
Decreased appetite: 20-30% reported in early studies - melanocortin pathway crossover with MC4R appetite signaling; usually transient
Spontaneous erections in men: documented signal even in pure tanning trials, ~30-40% of male participants in Hadley/Dorr studies
Hyperpigmentation of moles, freckles, lips, gums, nipples: dose-dependent, develops over weeks to months of use, partially reversible after discontinuation
New nevi (mole) formation: reported in case series of long-term subjects
Yawning: characteristic melanocortin agonism signature
Case reports of melanoma in heavy long-term MT2 subjects (Cardones & Grichnik 2009, Langan et al 2009): causation NOT established, but the safety debate centers on whether MT2 accelerates transformation of existing atypical nevi or just makes them harder to monitor visually

The Research

Peer-reviewed studies and clinical guidelines - tap any to read the source.

PubMedLevine N et al, Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin, JAMA 1991

original Hadley/Levine UA Tucson phase 1 in humans, established 250-500 mcg dose-response

Read study ↗PubMedDorr RT et al, Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study, Life Sci 1996

early human PK and AE profile, documented spontaneous erections

Read study ↗PubMedHadley ME, Discovery that a melanocortin regulates sexual functions in male and female humans, Peptides 2005

Hadley's retrospective on MC4R sexual effect discovery from MT2 research

Read study ↗PubMedCardones AR, Grichnik JM, alpha-Melanocyte-stimulating hormone-induced eruptive nevi, Arch Dermatol 2009

eruptive nevi case report on MT2 user

Read study ↗PubMedLangan EA et al, Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?, Br J Dermatol 2010

melanoma case series and safety review