Melanotan II
Melanotan II is a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH), developed at the University of Arizona in the 1980s by Victor Hruby, Mac Hadley, and Robert Dorr. The original goal was photoprotection: a drug that could induce melanin production without requiring the UV damage that normally drives tanning, aimed at people at high risk of skin cancer. Its structure, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, is a lactam-bridged ring that resists the enzymatic breakdown that makes native alpha-MSH useless as a drug.
- class
- cyclic heptapeptide, non-selective melanocortin receptor agonist
- receptors
- MC1R (pigment), MC3R and MC4R (libido, appetite), MC5R
- route
- subcutaneous
- plasma half-life
- roughly 1 hour, though pigmentation persists for weeks
- typical dose
- 250 mcg loading, 500 mcg to 1 mg weekly maintenance
- storage
- lyophilized refrigerated or frozen; reconstituted 2–8°C, 28-day max
Melanotan II Reconstitution & Dosage Protocol
weekly dose · reduces side effects| Phase | Window | Weekly dose | Draw (U-100, 2mL BAC) | Note |
|---|---|---|---|---|
| Tolerance test | Day 1 | 0.13 mg | 3 units· 0.03 mL | 125 mcg once, taken in the evening. At 5 mg/mL (10 mg vial in 2 mL BAC water) this is 0.025 mL, which is 2.5 units on a U-100 syringe. Nausea and facial flushing are the dose-limiting effects and they hit hardest on the first exposures, so a half dose on day one is the standard way to gauge them |
| Loading | Days 2–14 | 0.25 mg | 5 units· 0.05 mL | 250 mcg once daily, which is 0.05 mL or 5 units at 5 mg/mL. Dose at night so the nausea passes during sleep. Pigmentation is not immediate: visible darkening usually starts somewhere between day 7 and day 14 and requires some UV exposure to develop |
| Upper loading | As tolerated | 0.50 mg | 10 units· 0.10 mL | 500 mcg daily is the top of commonly reported loading, which is 10 units at 5 mg/mL. Going higher scales nausea, flushing, and spontaneous erections in men faster than it scales tanning, so most self-directed protocols stop here |
| Maintenance | After target tone | 0.50 mg | 10 units· 0.10 mL | 500 mcg to 1 mg once or twice weekly holds pigmentation once the desired tone is reached. Cumulative loading exposure is typically 5 to 10 mg total before switching to this phase |
| Skin check | Every cycle | 0.00 mg | 0 units· 0.00 mL | Photograph and map existing moles before starting and have a dermatologist review any new or changing pigmented lesion. Eruptive melanocytic nevi and darkening of existing nevi are documented case-report findings with this compound, not theoretical risks |
What is Melanotan II?
Melanotan II is a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH), developed at the University of Arizona in the 1980s by Victor Hruby, Mac Hadley, and Robert Dorr. The original goal was photoprotection: a drug that could induce melanin production without requiring the UV damage that normally drives tanning, aimed at people at high risk of skin cancer. Its structure, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, is a lactam-bridged ring that resists the enzymatic breakdown that makes native alpha-MSH useless as a drug.
The peptide is a non-selective agonist across the melanocortin receptor family, and that lack of selectivity explains both its effects and its problems. Agonism at MC1R on melanocytes drives eumelanin synthesis, which is the tanning effect. Agonism at MC3R and MC4R in the central nervous system drives the two large off-target effects: sexual arousal and appetite suppression. MC5R involvement is associated with sebaceous gland activity. One molecule therefore produces pigmentation, erections, nausea, and reduced hunger at overlapping doses, and there is no way to dose for one and avoid the others.
The erectile effect was not a side finding, it became its own drug. Wessells and colleagues published a double-blind placebo-controlled crossover study in J Urol in 1998 showing that subcutaneous Melanotan II initiated erections in men with psychogenic erectile dysfunction, followed by a 2000 Urology paper covering organic erectile dysfunction. That line of work led to bremelanotide (PT-141), the deaminated metabolite of Melanotan II, which is more selective and which the FDA approved in 2019 for hypoactive sexual desire disorder in premenopausal women. Melanotan II itself was never approved for anything, anywhere.
Human dosing data is thin and old. The Dorr 1996 pilot phase I study in Life Sci gave subcutaneous Melanotan II to healthy volunteers and established the basic dose range along with the side effect profile: nausea in most subjects, facial flushing, stretching and yawning, and spontaneous erections in men. Plasma half-life is short, on the order of an hour, but that number is misleading in practice because melanin, once produced, persists for weeks. This is why maintenance dosing drops to once or twice weekly while loading is daily.
The safety picture is the reason to be cautious rather than casual. Because the peptide stimulates melanocytes systemically, published case reports document eruptive melanocytic nevi, rapid darkening of existing moles, and changes in nevus morphology after use, including a 2009 Br J Dermatol report and a 2014 Eur J Dermatol case following a single injection. Langan and colleagues reviewed the broader clinical picture in Br J Dermatol in 2010. Compounding this, essentially all Melanotan II in circulation is unregulated grey-market material with no assay verification, and it is sold in the United States for research purposes only. Melanotan II is not sunscreen: it does not block UV, and any pigmentation it produces should not be treated as meaningful protection.