Melanotan II
MetabolicMT-II — Synthetic Peptide
Overview
Melanotan II (MT-II) is a cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (α-MSH) developed at the University of Arizona in the 1990s. It is a non-selective melanocortin receptor agonist that binds MC1R through MC5R, producing a range of physiological effects including skin pigmentation (tanning), sexual arousal, appetite suppression, and lipolysis. Melanotan II is the parent compound from which PT-141 (bremelanotide) was derived.
Despite never receiving regulatory approval in any jurisdiction, Melanotan II has been widely available through grey-market suppliers and has been self-administered by a substantial number of individuals seeking tanning effects. This unregulated use has generated both clinical data (through case reports and surveillance) and safety concerns. The peptide's non-selective melanocortin receptor activity produces broader effects than the more targeted PT-141, which was specifically developed to isolate the MC4R-mediated sexual function effects while minimizing MC1R-driven pigmentation.
Mechanism of Action
Melanotan II activates melanocortin receptors across the MC1R-MC5R family, with its diverse effects mapping to specific receptor subtypes. MC1R activation on melanocytes stimulates the cAMP/PKA pathway, upregulating tyrosinase and other melanogenic enzymes to increase eumelanin production. This produces skin darkening even in the absence of UV exposure, though UV radiation potentiates the effect. MC4R activation in the hypothalamus produces the dual effects of appetite suppression (through POMC/AgRP neuron modulation) and sexual arousal (through oxytocin and dopamine release in reward circuits).
MC3R activation contributes to metabolic effects including enhanced fatty acid oxidation, while MC5R activation influences sebaceous gland function. The non-selectivity of Melanotan II — in contrast to the MC4R-preferring PT-141 — is both its therapeutic advantage (broader metabolic effects) and its liability (more off-target effects). The cyclic structure incorporating D-phenylalanine provides resistance to enzymatic degradation and constrains the peptide into a bioactive conformation that mimics the pharmacophore of native α-MSH.
Research Dosing
Not approved for human use in any jurisdiction. Doses derived from clinical trial data. Nausea, facial flushing, and fatigue are common initial side effects. UV exposure potentiates melanogenic effect.
Nasal spray formulations studied but absorption is less reliable than subcutaneous injection. Bioavailability approximately 25-50% of SC route.
Research data only. These dosing ranges are derived from published studies, primarily in animal models. This is not medical advice. No peptide discussed on this site is approved for human therapeutic use unless otherwise noted.
Published Studies
Subcutaneous administration of Melanotan II to human volunteers
Dorr RT, Lines R, Levine N, et al. — Clinical Pharmacology and Therapeutics, 1996
First human trial of Melanotan II in 3 healthy volunteers. Subcutaneous doses of 0.01-0.025 mg/kg produced measurable increases in skin melanin density within 5 days without UV exposure. Side effects included nausea, facial flushing, and fatigue, all dose-dependent and self-limiting.
PMID: 8841154 →HumanSynthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study
Wessells H, Fuciarelli K, Hansen J, et al. — Journal of Urology, 1998
Double-blind crossover study showing subcutaneous Melanotan II induced clinically meaningful erections in 8 of 10 men with psychogenic erectile dysfunction, establishing the sexual arousal effects as centrally mediated through melanocortin receptors rather than peripheral vascular mechanisms.
PMID: 9679287 →ReviewClinical efficacy of Melanotan II: a systematic review
Nelson ME, Bryant SM, Aks SE — Clinical Toxicology, 2012
Systematic review examining both clinical trial evidence and adverse event reports for Melanotan II. Documented skin darkening efficacy but noted concerning reports of new or changed nevi, cardiovascular effects, and the emergence of unregulated grey-market supply chains.
PMID: 22390218 →