Maple Melanotan I (afamelanotide, [Nle4, D-Phe7]-alpha-MSH) and Melanotan II are synthetic analogues of alpha-melanocyte-stimulating hormone (alpha-MSH), a 13-amino acid endogenous peptide that regulates melanogenesis, energy homeostasis, and sexual function through melanocortin receptor signaling. Both compounds were originally developed at the University of Arizona as research tools for studying the melanocortin receptor system, and they remain among the most widely used melanocortin pathway research peptides in preclinical investigation.
Maple Research Labs supplies both Melanotan I and Melanotan II to Canadian laboratories, universities, and documented research buyers. Every batch ships with an independent third-party Certificate of Analysis confirming identity and purity.
For research purposes only. Not for human consumption. Not for diagnostic or therapeutic use.
Molecular Profiles
| Parameter | Melanotan I | Melanotan II |
|---|---|---|
| Full name | Afamelanotide, [Nle4, D-Phe7]-alpha-MSH | [Ac-Nle4, D-Phe7]-alpha-MSH(4-10) amide |
| CAS Number | 75921-69-6 | 121062-08-6 |
| Structure | Linear 13-amino acid peptide | Cyclic 7-amino acid lactam |
| Molecular Formula | C78H111N21O19 | C50H69N15O9 |
| Molecular Weight | 1646.9 Da | 1024.2 Da |
| MC receptor selectivity | MC1R preferring | Non-selective (MC1R, MC3R, MC4R, MC5R) |
| Purity | ≥99% (HPLC) | ≥99% (HPLC) |
| Storage | -20°C, lyophilized, desiccated | -20°C, lyophilized, desiccated |
The Melanocortin Receptor System
Five melanocortin receptor subtypes (MC1R through MC5R) mediate the diverse physiological effects of melanocortin peptides. Understanding the receptor distribution and function is essential for interpreting the differential activity profiles of Melanotan I and Melanotan II.
MC1R is expressed primarily on melanocytes and immune cells. Activation stimulates eumelanin synthesis through the cAMP/PKA/MITF signaling cascade, shifting the melanogenesis pathway from pheomelanin (red/yellow) to eumelanin (brown/black) production. MC1R is the primary target for melanogenesis research.
MC3R is expressed in the hypothalamus, gut, and placenta. MC3R is involved in energy homeostasis and metabolic regulation. Its activation modulates feeding behavior and energy partitioning in preclinical models.
MC4R is expressed predominantly in the CNS, particularly the hypothalamus, paraventricular nucleus, and spinal cord. MC4R activation regulates appetite, energy expenditure, and erectile function. MC4R is the target implicated in the sexual function effects observed in melanocortin research.
MC5R is expressed in sebaceous glands, adrenal glands, and various peripheral tissues. MC5R regulates exocrine gland function, including sebum production.
Melanotan I: MC1R-Preferring Linear Analogue
Melanotan I (afamelanotide) is a full-length 13-amino acid linear analogue of alpha-MSH with two modifications: norleucine at position 4 (replacing methionine, preventing oxidative degradation) and D-phenylalanine at position 7 (conferring DPP-IV resistance and increasing receptor binding affinity). These modifications extend the biological half-life from minutes (native alpha-MSH) to approximately 30 minutes while maintaining the MC1R-preferring selectivity profile of the parent peptide.
Afamelanotide received EMA approval in 2014 (Scenesse) for the prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP), making it the first melanocortin receptor agonist to receive regulatory approval for a non-cosmetic indication. In research contexts, Melanotan I serves as the reference MC1R agonist for melanogenesis, photoprotection, and immune modulation studies.
Melanotan II: Non-Selective Cyclic Analogue
Melanotan II is a truncated, cyclic analogue comprising alpha-MSH residues 4-10 with a lactam bridge between positions 4 and 10 (Asp-His-D-Phe-Arg-Trp-Lys cyclization). The cyclic structure confers significantly higher metabolic stability and altered receptor selectivity compared to the linear Melanotan I. Melanotan II activates MC1R, MC3R, MC4R, and MC5R with varying potency, producing a broader pharmacological profile than the MC1R-preferring Melanotan I.
The non-selective receptor engagement of Melanotan II is responsible for its observed effects on both melanogenesis (via MC1R) and sexual function in preclinical models (via MC4R). This dual activity made Melanotan II the lead compound for the development of bremelanotide (PT-141), a modified version that was optimized for MC4R selectivity and advanced through clinical trials for hypoactive sexual desire disorder.
Melanotan I vs. Melanotan II: Research Comparison
| Feature | Melanotan I | Melanotan II |
|---|---|---|
| Structure | Linear (13 amino acids) | Cyclic (7 amino acids, lactam bridge) |
| MC1R activity | High (preferring) | High |
| MC3R activity | Low | Moderate |
| MC4R activity | Low | High |
| MC5R activity | Low | Moderate |
| Melanogenesis | Primary research use | Yes, plus additional MC receptor effects |
| Regulatory status | EMA approved (Scenesse, EPP) | Not approved; led to PT-141 development |
| Research focus | MC1R pharmacology, photoprotection | Multi-receptor MC signaling, sexual function |
Product Specifications
| Specification | Melanotan I | Melanotan II |
|---|---|---|
| Purity | ≥99% (HPLC verified) | ≥99% (HPLC verified) |
| Available Sizes | 10mg | 10mg |
| Form | Lyophilized powder | Lyophilized powder |
| COA | Third-party COA included | Third-party COA included |
| Shipping | Same-day from Canada | Same-day from Canada |
| Use | Research only | Research only |
Melanotan I product page | Melanotan II product page | Certificates of Analysis
Frequently Asked Questions
What is the difference between Melanotan I and Melanotan II?
Melanotan I is a linear 13-amino acid analogue of alpha-MSH that preferentially activates MC1R (melanogenesis). Melanotan II is a cyclic 7-amino acid truncated analogue that activates MC1R, MC3R, MC4R, and MC5R non-selectively. The broader receptor profile of Melanotan II produces effects beyond melanogenesis, including MC4R-mediated activity. Melanotan I received EMA approval (Scenesse) for erythropoietic protoporphyria; Melanotan II has not received regulatory approval but led to the development of PT-141 (bremelanotide).
What are melanocortin receptors?
Melanocortin receptors (MC1R-MC5R) are a family of G-protein coupled receptors that mediate the effects of melanocortin peptides including alpha-MSH, ACTH, and their synthetic analogues. MC1R regulates melanogenesis, MC3R and MC4R regulate energy homeostasis and sexual function, and MC5R modulates exocrine gland function. Melanotan I primarily activates MC1R, while Melanotan II activates multiple subtypes.
Can I buy Melanotan research peptides in Canada?
Yes. Maple Research Labs supplies both Melanotan I (10mg) and Melanotan II (10mg) from within Canada. Both compounds are verified at 99%+ purity via independent third-party HPLC analysis and ship with batch-specific Certificates of Analysis. All melanocortin peptides are sold exclusively for research purposes.
Related Research Resources
- Melanotan I vs Melanotan II Comparison — Detailed head-to-head analysis
- GHK-Cu Research — Gene expression modulation and tissue remodeling
- Purity Testing Methods — HPLC and mass spectrometry explained
- All Research Peptides — Complete compound catalog
For research purposes only. Not for human consumption. Not for diagnostic or therapeutic use.