Melanotan II

What is Melanotan II?

Melanotan II (MT-II) is a synthetic analog of alpha-melanocyte stimulating hormone (α-MSH) that was originally developed at the University of Arizona for potential treatment of skin conditions and sexual dysfunction. It is a cyclic lactam peptide that activates melanocortin receptors, producing multiple physiological effects including skin tanning, appetite suppression, and enhanced libido.

Unlike its predecessor Melanotan I (afamelanotide), which is more selective for melanin production, Melanotan II has broader receptor activity and is particularly noted for its effects on sexual function in both men and women.

Important Warning: Melanotan II is not approved by the FDA or most regulatory agencies. It carries significant safety concerns including potential links to melanoma development. This information is for educational purposes only.

Development History

Origins

Melanotan II was developed in the 1990s at the University of Arizona by researchers seeking a tanning agent that could provide sun-free melanin production as protection against skin cancer and UV damage.

Timeline

• 1980s: Research into MSH analogs begins
• 1991: Melanotan II synthesized at University of Arizona
• 1996: Initial human trials conducted
• 2000s: Widespread attention due to tanning and sexual effects
• 2007-Present: Regulatory warnings issued by multiple agencies
• Present: Remains unapproved; PT-141 (derivative) approved for HSDD

Regulatory History

Multiple regulatory agencies have issued warnings:

• FDA issued warnings about unapproved tanning products
• MHRA (UK) warnings about unlicensed products
• TGA (Australia) warnings about health risks
• Despite warnings, remains available through unregulated sources

Molecular Profile

Chemical Structure

Melanotan II is a cyclic heptapeptide:

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

Key Features

• Cyclic structure: Lactam bridge between Asp and Lys
• D-Phenylalanine: Increases stability and receptor selectivity
• Norleucine substitution: Replaces methionine to prevent oxidation
• N-terminal acetylation: Improves stability

Molecular Data

Mechanism of Action

Melanocortin Receptor System

Melanotan II activates multiple melanocortin receptors (MCRs):

Tanning Mechanism (MC1R)

Process:

1. MT-II binds MC1R on melanocytes
2. Activates cAMP signaling pathway
3. Increases tyrosinase activity
4. Stimulates melanin production (melanogenesis)
5. Melanin transferred to keratinocytes
6. Visible skin darkening occurs

Key Features:

• Works without UV exposure
• Effect enhanced by sun exposure
• Produces eumelanin (protective dark pigment)
• Results in tan that develops gradually

Sexual Function (MC4R)

Central Mechanism:

1. MT-II crosses blood-brain barrier
2. Activates MC4R in hypothalamus and limbic system
3. Initiates arousal and erectile response
4. Works independently of peripheral vascular effects

Effects Observed:

• Enhanced libido in both sexes
• Erectile function improvements
• May work when PDE5 inhibitors fail
• Central vs peripheral mechanism

Appetite Effects (MC3R/MC4R)

• Activation of central melanocortin receptors
• Associated with appetite suppression
• Part of natural satiety signaling
• May contribute to weight effects

Observed Effects

Tanning

Characteristics:

• Gradual tan development over 1-2 weeks
• Deeper, longer-lasting than sun tan
• Even coverage possible
• Works without UV (enhanced with UV)
• Tan persists longer after cessation

Sexual Function

In Men:

• Spontaneous erections reported
• Enhanced erectile function
• Increased libido
• May help non-responders to viagra

In Women:

• Increased sexual desire
• Enhanced arousal
• Effects led to development of PT-141 (Vyleesi)

Other Reported Effects

• Appetite suppression
• Facial flushing
• Nausea (especially initially)
• Fatigue/yawning
• Mole darkening (concerning)

Safety Concerns

Serious Risks

Melanoma Concerns:

The most significant safety concern:

• Stimulation of melanocytes may affect atypical moles
• Reports of melanoma in users (causal link unclear)
• Existing moles may darken or change
• May mask or promote skin cancers
• Dermatologists recommend against use

Other Serious Risks:

• Cardiovascular effects possible
• Blood pressure changes
• Nausea and vomiting
• Facial flushing
• Unknown long-term effects

Common Side Effects

Typical:

• Nausea (very common, especially initially)
• Facial flushing (common)
• Fatigue/drowsiness
• Headache
• Injection site reactions

Less Common:

• Spontaneous erections (can be problematic)
• Dizziness
• Stomach cramps
• Mood changes

Regulatory Warnings

Multiple agencies have issued warnings:

• FDA: Unapproved, potentially dangerous
• MHRA (UK): Public warning issued
• TGA (Australia): Strongly advised against use
• Health Canada: Warning about unlicensed products

Comparison: Melanotan II vs Melanotan I

Why the Difference?

• MT-I (afamelanotide) was designed for greater MC1R selectivity
• MT-II's cyclic structure provides broader receptor activation
• MT-I was successfully developed through FDA approval pathway
• MT-II remained in the unregulated market

PT-141 (Bremelanotide): The Approved Derivative

Development from MT-II

PT-141 (bremelanotide) is a modified version of Melanotan II:

• Developed specifically for sexual dysfunction
• FDA approved in 2019 as Vyleesi
• Approved for hypoactive sexual desire disorder (HSDD) in premenopausal women
• Removes tanning effects while preserving sexual function

Key Differences

Research and Academic Studies

Clinical Trials Conducted

Several clinical studies have examined MT-II:

Sexual Function Studies:

• Demonstrated erectile effects in men
• Showed increased arousal in women
• Effects observed regardless of psychological state
• Works through central mechanism

Tanning Studies:

• Confirmed melanin production increase
• Showed effectiveness without UV
• Demonstrated persistence of tan
• Raised safety concerns about mole changes

Current Research Status

• Active research largely shifted to PT-141
• Ongoing concerns about melanocyte stimulation
• No path to FDA approval for MT-II currently
• Academic interest in melanocortin system continues

Legal and Availability Status

Regulatory Status Worldwide

United States:

• Not FDA approved
• Cannot be legally sold for human use
• Available as "research chemical"
• Classified as unapproved new drug

United Kingdom:

• Unlicensed medicine
• Illegal to sell for human use
• MHRA warnings issued

Australia:

• Not approved by TGA
• Prescription-only if imported
• Warnings issued about health risks

Europe:

• Not approved by EMA
• Various national regulations apply

Availability

Despite regulatory status:

• Widely available online
• Sold as "research chemical" or "tanning injection"
• Quality and purity vary significantly
• No quality control or oversight

Frequently Asked Questions

Does Melanotan II protect against skin cancer?

While the premise of MT-II development was UV protection through melanin, the reality is more complex. The stimulation of melanocytes that produces tanning may also stimulate abnormal cells. Multiple dermatological organizations recommend against its use. Natural melanin from sun exposure and MT-II-induced melanin may not provide equivalent protection.

How long does the tan last?

The tan can persist for several months after stopping use, though it gradually fades. This is because the melanin produced is incorporated into skin cells. However, maintenance doses are typically used by those seeking persistent effects.

Is Melanotan II legal to buy?

The legality is complex. In most countries, it's not approved for human use but may be sold as a "research chemical." Purchasing for personal use exists in a legal gray area in many jurisdictions. It cannot be legally marketed or sold for human consumption.

Why wasn't Melanotan II approved like PT-141?

MT-II's broader receptor profile and multiple effects (tanning, sexual, appetite) make it less suitable for targeted therapeutic development. PT-141 was specifically developed to isolate the sexual function effects for a defined clinical indication. Additionally, the melanoma concerns with MT-II's tanning effects present significant safety hurdles.

Can women use Melanotan II?

While women do use MT-II and experience both tanning and sexual effects, the safety concerns apply equally. The development of PT-141/Vyleesi specifically for women's sexual health provides an FDA-approved alternative for sexual dysfunction.

Key References

1. Hadley, M.E., & Dorr, R.T. (2006). "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization." Peptides, 27(4), 921-930.

2. Wessells, H., et al. (2000). "Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study." Journal of Urology, 160(2), 389-393.

3. King, S.H., et al. (2007). "Melanocortin receptors, melanotropic peptides and penile erection." Current Topics in Medicinal Chemistry, 7(11), 1098-1106.

4. Nelson, M.E., et al. (2012). "Melanotan II." Drug Testing and Analysis, 4(11), 897-902.

5. Brennan, R., et al. (2014). "Melanotan II: a review of the literature on safety and side effects." Journal of Plastic, Reconstructive & Aesthetic Surgery, 67(5), 685-686.

Summary

Melanotan II remains one of the most controversial peptides in the research chemical market. While its effects on tanning and sexual function are well-documented, significant safety concerns—particularly regarding melanocyte stimulation and potential melanoma risk—have prevented its approval by regulatory agencies.

Key Points:

• Classification: Synthetic α-MSH analog, melanocortin receptor agonist
• Effects: Tanning, enhanced libido, appetite suppression
• Mechanism: MC1R (tanning), MC4R (sexual function)
• FDA Status: Not approved; multiple regulatory warnings issued
• Safety: Significant concerns about melanoma, mole changes
• Alternative: PT-141 (bremelanotide) approved for HSDD

The development of PT-141 from MT-II research demonstrates how specific effects can be isolated for legitimate therapeutic use. Those seeking tanning or sexual function effects should be aware of the significant safety concerns and regulatory status of Melanotan II.