Melanotan II

What Is Melanotan II?

Melanotan II is a synthetic, cyclic analog of alpha-MSH that binds several melanocortin receptors rather than one. Case-report authors describe it as a non-selective melanocortin-receptor agonist whose effects in humans include increased skin pigmentation, spontaneous penile erection and sexual stimulation.^[1]

Its pigmentary effect is attributed to interaction with the melanocortin-1 receptor (MC1R) in skin, which induces hyperpigmentation.^[2] It is also described as a melanocortin-4 receptor (MC4R) agonist, a property that has led researchers to use it as a pharmacological tool for stimulating oxytocin-related activity in animal models.^[3]

Melanotan II has never been approved as a drug. Melanocortin analogs of this type have been used illegally for artificial tanning and have also been suggested as possible agents for erectile dysfunction.^[4] Much of the human literature therefore consists of case reports and surveys of unsupervised use rather than controlled trials.

Chemical Structure and Molecular Identity

Melanotan II is a seven-residue cyclic peptide, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, in which a lactam bond between the side chains of aspartic acid and lysine closes the ring. PubChem (CID 92432) lists the molecular formula C50H69N15O9 and a molecular weight of 1024.2 g/mol. The CAS number is 121062-08-6.

The ring encloses the His-D-Phe-Arg-Trp sequence, the same central segment found in afamelanotide (Melanotan I). The N-terminus carries an acetylated norleucine, a non-standard amino acid, and the C-terminus is a lysinamide. Because of the cyclic structure, the D-phenylalanine and the norleucine, the sequence cannot be written in standard one-letter code.

Melanotan II is structurally almost identical to bremelanotide: PubChem records show the same cyclic backbone, with bremelanotide carrying a free C-terminal carboxylic acid where Melanotan II has an amide. That single change gives bremelanotide the formula C50H68N14O10.

Comparison with Melanotan I

Research History and Development

Melanotan II emerged from melanocortin peptide research as a compact, cyclic alpha-MSH analog, and was investigated for both tanning and sexual-function effects. Its ability to cause spontaneous erections led to suggestions that melanocortin analogs could be developed for erectile dysfunction.^[4][1]

Over recent decades, the compound has become better known outside the laboratory. Unregulated acquisition of Melanotan II through the internet and other outlets became popular for use as a tanning agent, and clinicians began reporting adverse events in users.^[2] A 2026 review placed it among unapproved peptides, alongside BPC-157 and TB-500, that are used without prescriptions and lack established human safety profiles.^[5]

In parallel, laboratory research has continued to use Melanotan II as a melanocortin probe. Recent studies have examined it in mouse and zebrafish behavioral models^[3][6] and as a scaffold for new peptide-stapling chemistry.^[7]

Mechanisms Studied in Research

Melanotan II activates multiple melanocortin receptors; research has focused on MC1R-driven pigmentation and on central MC4R-linked effects on behavior and sexual function.^[1]

Pigmentation via MC1R

Like alpha-MSH, Melanotan II acts on MC1R to induce skin hyperpigmentation, which is the basis of its unregulated use as a tanning agent.^[2]

Central melanocortin signaling

Researchers studying autism-like behavior in mice chose Melanotan II as an MC4R agonist to stimulate oxytocinergic activity, building on evidence that oxytocin modulates social adaptation.^[3] In zebrafish, Melanotan II was used to target melanotropin receptors in a study of diet-related behavior.^[6]

Receptor binding of modified analogs

A 2024 chemistry study developed tryptathionine and 2,2′-bis-indole peptide staples, motifs borrowed from natural products, and applied them to Melanotan II, using chemoselective stapling of alpha-MSH-based sequences. Both classes of stapled peptides showed nanomolar binding affinities (Ki), with one analog reaching a sub-nanomolar Ki value.^[7]

Proposed mechanisms of toxicity

For renal injury reported in users, authors have proposed both a thrombotic pharmacological influence and a possible direct toxic effect on renal tissue.^[1]

Key Findings From Published Studies

Animal studies report behavioral effects of Melanotan II in models of autism and diet-induced memory impairment, while the human literature consists of case reports and observational data describing adverse events. No controlled human efficacy trials appear in the literature reviewed here.

Animal studies

• In a maternal immune activation mouse model of autism, Melanotan II rescued social behavioral metrics in adult male mice. In normal C57 mice it did not change social, anxiety-like or repetitive behaviors, but subacute treatment caused significant weight loss.^[3]
• In zebrafish, three weeks of a high-fat diet impaired recognition memory, raised anxiety and reduced exploration; Melanotan II reversed these changes, bringing behavior close to that of control animals.^[6]

Human case reports and observational studies

• A 2020 case report described renal infarction most likely attributed to Melanotan II and reviewed earlier reports of rhabdomyolysis and renal failure.^[1]
• A 2019 case report described low-flow priapism after melanotan use; the patient avoided surgical shunting but had not recovered erectile function at four-week follow-up.^[4]
• A systematic review of 179 patients with eruptive melanocytic nevi found that immunosuppressive agents, chemotherapy or melanotan accounted for 41% of suspected causes; 16% of cases had at least one histologically confirmed dysplastic nevus, and five associated melanoma cases were reported across all causes. The authors noted that the data did not allow assessment of malignant transformation risk.^[8]
• A case of melanoma in situ has been reported in association with melanotropic peptides sold as melanotan.^[9]
• A qualitative study of 623 online forum entries from 205 UK and Ireland participants found that users sought a tan before holidays or fitness competitions and identified misinformation, sunbed use and concerning practices.^[2]

Several case reports refer to melanotan without specifying which analog was used, so not every report can be assigned to Melanotan II with certainty.^[4][8][9]

Given published concerns about contamination and impurities in unregulated melanotan products, researchers typically verify identity and purity with HPLC and mass spectrometry certificates of analysis.

Given published concerns about contamination and impurities in unregulated melanotan products, researchers typically verify identity and purity with HPLC and mass spectrometry certificates of analysis.

Regulatory and Research Status

Melanotan II is not approved by the US Food and Drug Administration or, as far as the published literature shows, by any other regulator; it is an unlicensed compound with an unproven safety record.^[9][5] Its FDA Unique Ingredient Identifier (UNII UPF5CJ93X7) is a registration code, not an approval. Its close structural relative bremelanotide is an approved drug, but that approval does not extend to Melanotan II.

Reviewers have warned that unregulated peptides of this kind carry risks including product contamination and manufacturing impurities, and have urged clinicians to recognize their use.^[5] The authors of the forum study highlighted risks related to pigmented skin lesions, transmission of infectious diseases, contaminated products, polypharmacy and sunbed exposure.^[2]

As a research compound, Melanotan II remains a useful non-selective melanocortin agonist for receptor pharmacology, behavioral neuroscience and peptide chemistry. Open questions include its long-term effects on melanocytic lesions, the mechanisms behind reported renal events, and whether behavioral findings in mice and zebrafish translate to other models.^[8][1]