Melanotan II

Overview

Melanotan II (MT-II) is a synthetic cyclic peptide analog of alpha-melanocyte-stimulating hormone (α-MSH). Developed at the University of Arizona in the late 1980s, it was originally investigated as a potential preventive treatment for skin cancer by inducing protective melanogenesis.

While never approved for human use, Melanotan II has become widely known for its ability to produce skin tanning without UV exposure and its notable side effect of increasing sexual arousal. This dual action led to the development of PT-141 (bremelanotide), which isolated the sexual effects.

Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2

Mechanism of Action

Melanotan II is a non-selective melanocortin receptor agonist:

MC1R (Pigmentation)

• Primary receptor for tanning effects
• Stimulates melanocyte activity
• Increases eumelanin production
• Results in skin darkening independent of UV

MC3R/MC4R (Appetite/Sexual Function)

• Reduces appetite
• Increases sexual arousal and desire
• Effects on energy homeostasis

MC5R (Exocrine Function)

• May affect sebum production
• Role less well characterized

Melanin Production Pathway

1. MC1R activation on melanocytes
2. Increased cAMP production
3. CREB activation
4. Tyrosinase upregulation
5. Enhanced melanin synthesis
6. Transfer to keratinocytes

Research Summary

Clinical Studies (Limited)

University of Arizona Studies (1990s)

• Demonstrated melanogenesis in human subjects
• Noted sexual arousal as significant side effect
• LED to PT-141 development

Phase 1/2 Studies

• Showed dose-dependent tanning
• Confirmed erectile effects in men
• Nausea was dose-limiting factor

Preclinical Research

Key Observations

• Tanning occurs without UV exposure
• UV exposure enhances and accelerates effects
• Sexual effects consistent across studies
• Appetite reduction commonly noted

Why Not Approved

• Side effect profile concerns
• Uncontrolled melanin distribution (mole darkening)
• Cardiovascular effects observed
• Nausea at effective doses
• Long-term safety unknown

Pharmacokinetics

Melanin effects persist much longer than plasma half-life due to the sustained nature of melanogenesis.

Common Protocols

Note: Melanotan II is not approved for human use. The following represents protocols discussed in research communities, not medical recommendations.

Research Community Protocols

Loading Phase:

• Starting dose: 0.25mg
• Increase by 0.25mg every few days
• Target: 0.5-1mg daily
• Duration: 2-4 weeks or until desired tan

Maintenance:

• 0.5-1mg weekly to biweekly
• Or before sun exposure
• Frequency depends on individual response

Tanning Protocol

• Dose 30-60 minutes before UV exposure
• UV exposure accelerates melanin transfer
• Many report tan developing without UV
• Gradual approach minimizes nausea

Administration

Injection Method

• Subcutaneous injection
• Abdomen most common
• Insulin syringes (29-31 gauge)
• Rotate injection sites

Reconstitution

• Lyophilized powder + bacteriostatic water
• Common: 10mg + 2mL water = 5mg/mL
• Store reconstituted at 2-8°C
• Use within 4-6 weeks

Nasal Administration

• Some products marketed as nasal spray
• Bioavailability less predictable
• Less common than injection

Side Effects

Common (Expected)

• Nausea (very common, especially initially)
• Facial flushing
• Fatigue/drowsiness
• Spontaneous erections
• Darkening of existing moles
• Increased libido

Less Common

• Headache
• Dizziness
• Decreased appetite
• Yawning/stretching
• Injection site reactions

Serious Concerns

• Mole changes: Existing moles may darken or change
• New nevi: Reports of new moles appearing
• Uneven pigmentation: Facial darkening may be patchy
• Melanoma concerns: Theoretical - may mask or promote
• Cardiovascular: Blood pressure effects reported

Important Warnings

• Any mole changes should be evaluated by dermatologist
• Not studied in people with history of skin cancer
• Long-term effects unknown

Interactions

Contraindications (Theoretical)

• History of melanoma or atypical moles
• Cardiovascular disease
• Pregnancy/nursing
• History of skin cancer

Drug Interactions

• Other melanocortin peptides
• Blood pressure medications
• Erectile dysfunction medications

Precautions

• Fair skin individuals (unpredictable tanning)
• History of frequent sunburns
• Family history of melanoma
• Multiple atypical moles

Community Insights

The following represents aggregated reports from online communities and should not be considered medical advice or verified claims.

Commonly Reported Experiences

• Nausea most common complaint, especially early
• Tan develops even without sun exposure
• Sexual effects often pronounced
• Freckles and moles darken significantly
• Effects more dramatic in fair-skinned individuals

Practical Tips Shared

• Start very low to assess nausea tolerance
• Antihistamines (Benadryl) may reduce nausea
• Evening dosing allows sleeping through nausea
• Take on empty stomach (though may worsen nausea)
• UV exposure not required but accelerates results

Common Concerns

• Mole darkening worries many users
• Uneven facial pigmentation reported
• "Melanotan face" - dark patches
• Long-term safety frequently discussed
• Quality control with sources

Comparison to PT-141

• MT-II has stronger tanning effects
• PT-141 has less pigmentation side effects
• Sexual effects similar
• PT-141 FDA approved; MT-II is not

References

1. Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84. [PMID: 8637402]

2. Wessells H, et al. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000;12 Suppl 4:S74-9. [PMID: 11035391]

3. Langan EA, et al. The cutaneous biology of α-melanocyte-stimulating hormone and Melanotan II. Exp Dermatol. 2010;19(6):507-15. [PMID: 20163458]

4. Barnetson RS, et al. [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers. J Invest Dermatol. 2006;126(8):1869-78. [PMID: 16763549]

5. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-30. [PMID: 16412534]

6. ACMD (Advisory Council on the Misuse of Drugs). Consideration of the Novel Psychoactive Substances ('Legal Highs'). 2011.