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What Is Melanotan II?
Melanotan II (MT-II) is a synthetic cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (ฮฑ-MSH). Developed at the University of Arizona in the 1990s, it was originally created to induce tanning as a potential skin cancer prevention strategy by stimulating melanin production without UV exposure.
Melanotan II acts on multiple melanocortin receptors (MC1R-MC5R), producing various effects beyond tanning including appetite suppression and sexual arousal.
Key Characteristics
- Primary Effect: Melanogenesis (tanning without UV)
- Secondary Effects: Appetite suppression, sexual arousal
- Receptor Activity: MC1R, MC3R, MC4R, MC5R
- FDA Status: Not approved for any indication
Development Background
The research history of Melanotan II:
- Goal: Develop a tanning agent to protect fair-skinned people from UV damage
- Rationale: Melanin provides natural sun protection
- Discovery: Sexual side effects noted during initial human studies
- Outcome: Led to development of PT-141 (bremelanotide) for sexual dysfunction
Mechanism of Action
Melanocortin Receptor System
MT-II is a non-selective melanocortin agonist:
| Receptor | Location | Effect of MT-II |
|---|---|---|
| MC1R | Melanocytes (skin) | Melanin production โ tanning |
| MC3R | Brain, gut | Energy homeostasis, sexual function |
| MC4R | Brain (hypothalamus) | Appetite suppression, sexual arousal |
| MC5R | Sebaceous glands | Exocrine function |
Tanning Mechanism
How MT-II induces tanning:
- Binds to MC1R on melanocytes in the skin
- Activates cAMP signaling cascade
- Increases tyrosinase enzyme activity
- Stimulates eumelanin synthesis
- Results in darker pigmentation
Sexual Effects
The unexpected finding from early research:
- MC3R and MC4R activation in the brain
- Affects hypothalamic sexual response centers
- Produces spontaneous erections in men
- Increases arousal in both sexes
- Led to development of PT-141
Appetite Effects
- MC4R activation reduces appetite
- Similar mechanism to natural ฮฑ-MSH
- Promotes satiety signals
Research Findings
Tanning Studies
- Effective at inducing melanogenesis
- Tanning occurs even without UV exposure
- Enhanced tanning response when combined with UV
- Effects develop over days to weeks
Sexual Function Research
- Produced erections in clinical studies
- Effective in some men unresponsive to PDE5 inhibitors
- Increased female sexual arousal
- Central mechanism (brain) rather than vascular
Key Published Research
| Year | Focus | Key Finding | Reference |
|---|---|---|---|
| 1996 | Tanning | Induced tanning in humans | Levine et al. |
| 1998 | Sexual effects | Spontaneous erections noted | Wessells et al. |
| 2000 | Mechanism | CNS pathway confirmed | Hadley et al. |
| 2005 | Female arousal | Effects in women documented | Diamond et al. |
MT-II vs Melanotan I
Comparison
- Melanotan I (afamelanotide): Linear peptide, more selective for MC1R
- Melanotan II: Cyclic peptide, non-selective melanocortin agonist
- Tanning: Both effective
- Sexual effects: MT-II significant; MT-I minimal
- Status: MT-I (Scenesse) is approved in EU for specific condition
Safety Concerns
Important Safety Information
Melanotan II has significant safety concerns:
- Not FDA approved: No regulatory oversight of purity or quality
- Nausea: Very common, sometimes severe
- Facial flushing: Common
- Nevi changes: Can darken or change existing moles
- Melanoma concern: Theoretical risk of stimulating melanoma growth
- Blood pressure: Can cause increases
- Priapism: Prolonged erections reported
- Unknown long-term effects: Limited safety data
Common Side Effects
- Nausea (often severe initially)
- Facial flushing
- Fatigue/lethargy
- Injection site reactions
- Darkening of moles and freckles
- Spontaneous erections
- Appetite suppression
- White line effect (stretch mark tanning)
Regulatory Status
| Region | Status |
|---|---|
| United States | Not approved, not legal for human use |
| European Union | Not approved |
| Australia | Banned (TGA warning) |
| UK | Not approved (MHRA warnings) |
Legacy and Derivatives
MT-II research led to approved medications:
- PT-141 (Bremelanotide/Vyleesi): FDA-approved for female HSDD
- Afamelanotide (Scenesse): EU-approved for erythropoietic protoporphyria
- Setmelanotide: FDA-approved for rare genetic obesity disorders
Research Status
Melanotan II is not approved for human use in any country. Health authorities worldwide have issued warnings about its use. While the science of melanocortin agonism has led to approved medications, MT-II itself remains an unregulated research compound with significant safety concerns.
Summary
Melanotan II represents an important chapter in melanocortin research, demonstrating the broad effects of this receptor system on pigmentation, appetite, and sexual function. While MT-II itself has not achieved regulatory approval due to safety concerns and its non-selective receptor profile, it paved the way for more targeted drugs like PT-141 for sexual dysfunction and afamelanotide for photosensitivity disorders. The compound remains a subject of scientific interest but carries significant risks for human use.