Melanotane-2

What is Melanotane-2

Melanotane-2 is a synthetic cyclic heptapeptide and an agonist at several melanocortin receptors (MC1R, MC3R, MC4R, MC5R). It was developed at the University of Arizona in the late 1980s, originally to give people with fair skin protection from UV-related damage by stimulating melanin production.

Amino acid sequence: Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-NH2. Molecular weight: 1024.18 g/mol. CAS No 121062-08-6. Structurally very similar to PT-141 (bromelanotide), the difference lies in the terminal lysine (carboxyl group vs amide group).

Clinical development was never completed. Melanotane-2 does not have a pharmaceutical license. The related melanotan-1 (afamelanotide, scenesse) was approved for erythropoietic protoporphyria in the EU in 2014, but this is another molecule with a different profile.

Mechanism of action

MC1R activation on melanocytes is the main pathway responsible for the pigmentation effect. MC1R stimulates the synthesis of eumelanin, the dark pigment that is also responsible for UV protection. When used repeatedly, the skin becomes measurably darker, similar to a sunburn-free tanning effect.

In addition, Melanotane-2 activates MC3R and MC4R in the central nervous system, which modulates the sexual pleasure and erection circuits. Hence the frequent reports of erections and increased desire, similar to PT-141.

MC5R activation in sebaceous glands can increase sebum production, which can lead to acne. MC3R/MC4R in the hypothalamus also modulates satiety, with moderate appetite reduction effects.

The pigmentation effects are dose-dependent and cumulative. Without UV stimulation, only a slight effect is achieved, in combination with sun exposure a significantly darker browning is produced than without MT-2.

Areas of application in research

UV protection and tanning: Original development indication
Erythropoietic protoporphyria: Related afamelanotide allowed
Sexual pleasure and erection problems: Off-label application, similar to PT-141
Obesity: MC4R activation with saturation effect
Skin diseases: Vitiligo studies, mixed results

Study situation

Early Phase 1 and Phase 2 studies were conducted in the 1990s and 2000s, after which commercial development was halted. Most of the available data comes from academic research or observational studies.

Important works:

Dorr et al. (Life Sciences, 1996): First clinical data on the pigmentation effect
Dorr et al. (Archives of Dermatology, 2000): Effect on skin pigmentation in healthy adults
Wessells et al. (Urology, 2000): Erection effects in men with psychogenic ED
Multiple case reports: skin lesions, new nevi and suspected melanoma diagnoses in non-pharmaceutical users

What is clear: Melanotane-2 works biologically as expected (pigmentation, sexual effects). What remains unclear: long-term safety, especially with regard to melanocytic changes and melanoma risk.

Mixing (reconstitution)

Typical Vial sizes: 10 mg lyophilisate (most common form).

10 mg Vial with 1 ml bacteriostatic water → 10 mg/ml (corresponds to 1 mg per 0.1 ml)
10 mg Vial with 2 ml → 5 mg/ml for finer dosage
10 mg Vial with 5 ml → 2 mg/ml for very small doses

After mixing cooling 2 to 8 degrees, stability about 4 to 6 weeks. Lyophilisateeeee stable at -20 degrees over years.

Dosage range (research data)

From the research use community (no validated clinical protocols):

Charging phase:

Start with 0.25 mg, once daily, subcutaneously
Slow increase to 0.5-1 mg per day over 1-2 weeks
UV exposure (sun or solarium) enhances the pigmentation effect
batch phase typically 2 to 4 weeks until desired pigmentation is achieved

Maintenance phase:

1 mg, once or twice a week
Only with occasional UV exposure to maintain pigmentation

Higher single doses drastically increase the frequency of side effects (nausea, vomiting).

Side effects

From clinical studies and case reports:

Nausea (very common, especially in the first few days)
Vomiting
Hot flashes and flushing
Spontaneous erections in men (often unexpected, long-lasting)
Temporary fatigue after injection
Appetite reduction
Darkening of existing moles and freckles
New pigment stains (lentigines)
Acne, increased sebum flow
In isolated cases, reports of atypical melanocytic lesions and melanoma

Melanocytic risk is the central safety aspect. Several case reports describe new or changed nevi in MT-2 users. A direct causal relationship is not established, but the biological plausibility is high: MC1R activation can theoretically affect tumorigenesis in melanocytes.

Half-Life and Pharmacokinetics

Elimination half-life: about 30 to 60 minutes. Bioavailability subcutaneously high. Maximum plasma level after about 30 minutes.

metabolism via peptidic degradation processes. No relevant CYP interactions. Excretion Renal and Biliary.

The biological effects (especially pigmentation) last far longer than the plasma half-life because they are mediated by melanin synthesis, which takes days to weeks.

Frequent questions

How Fast Does Melanotane-2 Whererk? Pigmentation typically becomes visible after 2 to 4 weeks, depending on dose and UV exposure. Sexual effects often occur after the first doses.

Does MT-2 protect against sunburn? Theoretically yes, through increased melanin production. Practically, protection is not reliable enough to replace sunscreen. The tan is not a complete UV protection.

What is the risk of melanoma? Not quantifiable with current data. Biologically plausible, but no controlled long-term studies. Existing nevi should be dermatologically documented before and during use.

What to do about the nausea? Low initial dose (0.25 mg, in the evening, if necessary with antiemetic. The nausea decreases in most users after 1 to 2 weeks.

Is MT-2 the same as Melanotan-1? No. Melanotan-1 is afamelanotide (Scenesse, approved for EPP), a related but different peptide with a more selective MC1R effect and fewer central effects.

Can I drop MT-2 and keep the tan? The tan fades after discontinuation for 1 to 3 months, similar to a normal tanning phase. Some hyperpigmentations can remain long-term or permanent.

Legal status U.S.

As of 2026: Melanotane-2 does not have a pharmaceutical license in Germany, Austria and Switzerland. Sales take place in the research-use-only rail, which is a legal grey area when applied to humans.

Several EU authorities (UK, Norway, Sweden) have issued active warnings about MT-2, in particular due to the risk of melanoma and the often poor product quality on the research use market.

WADA status: Melanocortin agonists are currently not explicitly on the prohibited list. Status can change.

Own import: §73 AMG restrictions on therapeutic or cosmetic intention.

Related compounds

afamelanotide (Melanotan-1, Scenesse)Approved for EPP
PT-141 (bromelanotide)MC4R-selective, less pigmentation, stronger sexual effects
α-MSH: Body’s own melanocortin hormone

Note: All information is for research information only. These peptides are not approved as medicines in Germany. The contents do not replace medical advice. Application to humans is not legally covered in Germany.