Melanotan I vs IIPharmacology, Safety & Research

Two synthetic analogs of the same natural hormone, developed in the same Arizona laboratory, with radically different fates. Melanotan I became afamelanotide (Scenesse) — FDA/EMA-approved for erythropoietic protoporphyria, with 10+ years of safety data across 1,000+ patients. Melanotan II became a gray-market tanning peptide banned in every major regulatory jurisdiction.

The divergence traces to a single structural decision. MT-I is a linear peptide selective for MC1R (the skin pigmentation receptor). MT-II is a cyclic peptide that activates four of five melanocortin receptor subtypes indiscriminately — including brain receptors controlling appetite and sexual arousal. MT-I is a single-purpose key; MT-II is a master key that opens doors you may not want opened.

The appetite suppression and erectile effects that made MT-II popular in bodybuilding communities are not features — they are pharmacological proof of non-selective CNS receptor activation. This article covers the receptor pharmacology, clinical evidence for MT-I, safety signals between the two compounds, and next-generation melanocortin agents that may make this comparison obsolete.

At a Glance

What Melanotan Actually Is

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Melanotan refers to two synthetic analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), a natural tridecapeptide that regulates skin pigmentation through melanocortin-1 receptor (MC1R) activation on melanocytes — the cells that produce pigment. Both analogs were developed at the University of Arizona, share the same core pharmacophore, and incorporate two amino acid substitutions that make them far more stable and potent than the native hormone. They differ in length, shape, receptor selectivity, and regulatory fate.

Alpha-MSH degrades rapidly in circulation — plasma half-life measured in minutes — rendering it impractical as a drug.^5 In 1980, Tomi Sawyer, Victor Hruby, and Mac Hadley synthesized a modified version with two key changes: replacing methionine at position 4 with norleucine (preventing oxidative degradation) and substituting L-phenylalanine at position 7 with the D-isomer.^5,^6 The D-Phe7 substitution increased receptor binding approximately 1,000-fold and conferred protease resistance by forming an additional hydrogen bond with the TM2 domain of MC1R.^6 This linear tridecapeptide — [Nle4, D-Phe7]-alpha-MSH — became Melanotan I, later developed clinically as afamelanotide.

Nine years later, a second compound emerged from the same laboratory. Al-Obeidi, Hadley, and Hruby truncated alpha-MSH to its minimal active core — the His-Phe-Arg-Trp tetrapeptide at positions 6 through 9 — and cyclized the sequence with a lactam bridge between aspartic acid and lysine side chains, producing a cyclic heptapeptide: Melanotan II (also referred to as melanotan 2 or MT-2).^7 The cyclization increased enzymatic stability beyond that of the linear analog. It also eliminated meaningful receptor selectivity, creating an agonist — a molecule that activates a receptor — that binds four of the five melanocortin receptor subtypes with roughly equivalent affinity.^8

The first became an FDA-approved drug. The second became a gray-market phenomenon.

MT-I vs MT-II — The Structural Divergence

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The structural difference between these two peptides functions like the difference between a single-purpose key and a master key. MT-I's linear shape fits one lock well — the MC1R receptor on skin cells that drives pigmentation. MT-II's cyclic shape fits multiple locks across the body, including receptors in the brain that control appetite and sexual arousal. This is the origin of every downstream divergence: pharmacology, safety, regulation, and clinical utility.

MT-I preserves the full 13-residue alpha-MSH sequence (Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2). Its linear architecture retains approximately 10-fold selectivity for MC1R over other melanocortin receptors — modest pharmacologically, but sufficient to concentrate effects on cutaneous melanogenesis and photoprotection.^6 The linear peptide does not meaningfully cross the blood-brain barrier, which accounts for the absence of central nervous system effects in clinical use.^9

MT-II condenses the pharmacophore into a 7-residue ring (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2). The lactam bridge constrains the peptide backbone, increasing proteolytic stability but also eliminating receptor discrimination. MT-II activates MC1R, MC3R, MC4R, and MC5R with sub-nanomolar to low-nanomolar affinity.^8 Its cyclic structure confers sufficient lipophilicity to cross the blood-brain barrier, enabling direct activation of hypothalamic MC4R — the receptor subtype mediating appetite regulation and sexual arousal.^10

Neither peptide activates MC2R, the ACTH-specific adrenal receptor. This means neither compound triggers cortisol synthesis — an important safety boundary.^6,^8

Pharmacokinetic Comparison

The pharmacokinetic profiles diverge as sharply as the structures.

Afamelanotide is administered as a 16 mg bioresorbable subcutaneous (under-the-skin) implant every 60 days. The implant provides controlled release: median Tmax at approximately 36 hours, with over 90% of drug liberated by day 5 and plasma levels undetectable by day 10.^9,^11 The intrinsic elimination half-life of the free peptide is approximately 30 minutes, but the slow-release formulation yields an apparent half-life of roughly 15 hours through flip-flop kinetics.^9

MT-II, by contrast, is rapidly absorbed after subcutaneous injection (absorption half-life 0.07-0.79 hours) with elimination half-life of 0.8-1.7 hours.^10 Nasal spray administration — the route popularised on social media — has substantially lower and more variable bioavailability than subcutaneous injection. No published clinical trial has used the intranasal route, and no quantitative pharmacokinetic comparison between nasal and subcutaneous delivery exists in the literature.

Despite its short pharmacokinetic presence, afamelanotide's melanogenic effects persist for weeks beyond the period of detectable drug levels, reflecting the time required for melanin turnover in the epidermis. No late effects have been reported in volunteers followed for 25 years after first exposure.^4,^9

How Melanocortin Receptors Shape the Effects

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The melanocortin receptor family comprises five subtypes (MC1R through MC5R), each with distinct tissue distribution and function. MT-I preferentially activates MC1R, confining its effects largely to melanogenesis and DNA repair. MT-II activates MC1R through MC5R non-selectively, producing tanning, sexual arousal, appetite suppression, and exocrine effects simultaneously — a pharmacological breadth that proved too broad for targeted clinical development.

MC1R — Melanogenesis and DNA Repair. Both peptides activate MC1R on melanocytes, driving eumelanin synthesis (the brown-black pigment that absorbs UV radiation and scavenges reactive oxygen species). MC1R activation also enhances nucleotide excision repair of UV-induced DNA damage — a photoprotective mechanism independent of pigment production.^4,^6 This DNA repair function connects to the broader cellular maintenance axis explored in the NAD+ guide. Loss-of-function MC1R variants (R151C, R160W, D294H), prevalent in fair-skinned populations, are established melanoma risk factors precisely because they impair both eumelanin production and DNA repair capacity.^4

MC3R and MC4R — Central Nervous System Effects. MC4R activation in the hypothalamus mediates appetite suppression and sexual arousal. MC3R modulates energy homeostasis — the body's system for balancing energy intake and expenditure — and contributes to erectile signalling.^10,^12 These effects are predominantly relevant to MT-II because the cyclic peptide crosses the blood-brain barrier; MT-I's linear structure and limited CNS penetration confine its actions to the periphery.^9

MC5R — Exocrine Effects. MC5R, expressed in exocrine glands, modulates sebaceous secretion and may contribute to fat breakdown. MT-II activates this receptor; the clinical significance remains uncertain.^8

MC2R — The Safety Boundary. MC2R is the ACTH-specific receptor responsible for adrenal steroidogenesis (cortisol production). Neither MT-I nor MT-II activates MC2R (Ki > 1 microM), meaning neither compound triggers cortisol release.^6,^8 This is a non-trivial safety feature for peptides with broad melanocortin activity.

The non-selectivity of MT-II is both its pharmacological interest and its clinical liability. The tanning effect attracted consumer demand, but the concurrent MC4R-mediated erectile, appetite, and CNS effects — combined with MC3R and MC5R activity of uncertain long-term significance — created a side-effect profile incompatible with any single therapeutic indication.

Clinical Evidence — What the Trials Show

Afamelanotide: Phase III Data in Erythropoietic Protoporphyria

Afamelanotide's clinical programme for EPP — a rare inherited porphyria causing acute phototoxicity on light exposure — represents the most rigorous investigation of any melanocortin agonist: three Phase III randomised controlled trials enrolling 244 patients across US and European sites.^1

The pivotal US trial (CUV039, n=93) demonstrated that patients receiving three afamelanotide implants every 60 days spent a median of 64.1 hours in pain-free direct sunlight over 180 days, compared to 40.5 hours for vehicle controls (P=0.04).^1 The European trial (CUV029, n=74) showed a more pronounced effect over 270 days: median pain-free sunlight of 6.0 hours versus 0.75 hours for vehicle (P<0.05), with phototoxic reactions reduced from 146 to 77 events (P=0.04).^1 A third trial (CUV017, n=91) demonstrated significant reductions in pain frequency (P=0.0023) and average pain severity (P=0.0017) over 12 months.^1,^13

Long-term data are equally consistent. Biolcati and colleagues followed 115 EPP patients for up to 8 years on afamelanotide, documenting quality-of-life scores rising from 31% to 74% of maximum — a gain sustained throughout the entire observation period.^2 Adverse events were predominantly mild: nausea, headache, and localised hyperpigmentation at the implant site.

The FDA granted priority review and orphan drug designation, approving Scenesse in October 2019.^14 The EMA authorised the drug in 2014 under exceptional circumstances and in September 2025 removed the 4-implant-per-year cap, harmonising with US labelling for year-round treatment.^15

Beyond EPP, a Phase II vitiligo trial (n=55, Fitzpatrick skin types III-VI) showed that afamelanotide combined with narrowband UV-B phototherapy achieved 48.6% repigmentation at day 168 versus 33.3% with NB-UVB alone, with significantly faster onset on the face and upper extremities.^16 Phase III trial CUV105, enrolling over 200 patients as of May 2025, will evaluate afamelanotide for vitiligo as both monotherapy and adjunctive therapy — the first systemic non-immunosuppressive agent trialled for repigmentation.^17

Melanotan II: Phase I and Small Studies

MT-II's human evidence base is qualitatively different. The only formal clinical trial is Dorr and colleagues' 1996 Phase I study: a single-blind, alternating-day, placebo-controlled trial in three male volunteers receiving subcutaneous injections.^10 Observed effects included dose-dependent tanning, nausea, and — unexpectedly — spontaneous penile erections. This serendipitous discovery of MC4R-mediated sexual arousal redirected MT-II's development trajectory, eventually producing bremelanotide (PT-141), which received FDA approval in 2019 as Vyleesi for hypoactive sexual desire disorder.^18

The erectile response data from Wessells and colleagues, while drawn from small crossover studies (n=10-20), are pharmacologically notable: 8 of 10 men with psychogenic erectile dysfunction developed clinically apparent erections after MT-II administration, with mean tip rigidity exceeding 80% for 38 minutes versus 3 minutes on placebo (P=0.0045).^19 Increased sexual desire was reported after 68% of MT-II doses versus 19% of placebo doses.^20 A subsequent study in men with organic erectile dysfunction showed reduced efficacy, suggesting the MC4R-mediated mechanism is most effective in the absence of vascular pathology.^21

MT-II reduces meal size through central MC3R/MC4R activation, but tachyphylaxis — diminishing response with repeated dosing — of the anorectic effect occurs with chronic use, limiting sustained utility.^22 For appetite suppression with established clinical evidence, GLP-1 receptor agonists operate through an entirely different mechanism with Phase III data and FDA approval.

No Phase III trial has ever been conducted for MT-II in any indication.

Safety — The Melanoma Question

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The weight of evidence indicates that MC1R activation is photoprotective rather than oncogenic. The Addison's disease cohort — 3,299 patients with chronic MC1R activation over 40 years — shows a standardised incidence ratio for melanoma of 0.7, numerically below expected rates. Afamelanotide's clinical programme reports zero melanoma events across more than 1,000 patients over periods exceeding 10 years. All five melanoma cases reported in MT-II users involved confounding UV exposure or pre-existing risk factors.

The Mechanistic Argument

MC1R activation drives two distinct protective mechanisms: eumelanin synthesis, which absorbs UV radiation and scavenges reactive oxygen species, and — independently of pigmentation — enhanced nucleotide excision repair of UV-induced DNA damage.^4,^6 Loss-of-function MC1R variants are established melanoma risk factors because they impair both pathways.^4

Epidemiological Evidence

The Addison's disease cohort provides the strongest epidemiological signal. Patients with Addison's disease experience chronic MC1R activation through tonically elevated ACTH. A 40-year follow-up of 3,299 patients found a standardised incidence ratio for melanoma of 0.7 (95% CI: 0.2-1.6) — numerically below expected rates, though the confidence interval crosses unity.^4 This natural experiment in lifelong MC1R activation found no evidence of increased melanoma risk.

The afamelanotide clinical programme contributes concordant pharmacological data: across more than 1,000 patients exposed over periods extending beyond 10 years of continuous treatment, zero melanoma events have been reported.^2,^4 Many EPP patients increased their sun exposure substantially after treatment, making the zero-melanoma finding more meaningful than it might otherwise appear in a population that historically avoids sunlight.

MT-II Case Reports

Five published case reports describe melanoma in MT-II users.^4,^23,^24,^25,^26 In every case, confounding risk factors were present: concurrent tanning bed use, fair skin phenotype, family history of melanoma, or MC1R loss-of-function variants. One case involved a teenager with familial atypical multiple mole and melanoma syndrome who was using both MT-II and sunbeds.^24

The most parsimonious interpretation: MT-II users represent a self-selected population of sun-seekers, many with fair skin, who combine pharmacological melanogenesis with excessive UV exposure. The melanoma risk in these cases is more plausibly attributed to UV damage than to MC1R activation per se.

Two melanoma cases reported in the setmelanotide (Imcivree) programme — a related MC4R-selective agonist — both occurred in patients with pre-existing high risk factors and were detected early through mandated dermatologic monitoring, supporting a detection bias rather than drug-induced oncogenesis.^4

The documented dermatologic risk signal for MT-II is nevi changes: darkening of existing moles, eruption of new nevi including those with dysplastic histology, and melanonychia — changes reproduced across multiple independent case series.^23,^25,^26,^27

No formal animal carcinogenicity studies have been conducted for either peptide, a gap acknowledged in the Scenesse FDA label.^14

Serious Adverse Events (MT-II)

Nausea is the most common adverse event, dose-dependent, with 13% experiencing severe nausea at the preferred erectile dose.^10,^19 Beyond predictable pharmacological effects, case reports of unregulated use document:

• Rhabdomyolysis: A 39-year-old male injected 6 mg and presented with creatine phosphokinase peaking at 17,773 IU/L, requiring three days of intensive care.^28
• Renal infarction: A 45-year-old with approximately 27 mg cumulative exposure over 6 months developed right-sided renal infarction affecting approximately 50% of the kidney, likely through a vasoconstrictive or thrombotic mechanism.^29
• Priapism: Reported with overdose, consistent with the MC4R-mediated erectile mechanism.

These events occurred at doses far exceeding typical user protocols, but they underscore the inherent danger of unregulated self-dosing without medical oversight or quality-assured product.

The Gray Market and Product Quality Problem

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MT-II is illegal to sell in the United States, United Kingdom, and Australia, though it is not a DEA-scheduled controlled substance. The FDA classified it as Category 2 in 2023, barring it from compounding pharmacy preparation. Despite this, MT-II circulates widely through gray-market channels, with online peptide advertisements surging 208% in 2024 and marketplace sales growing 276% over five years.

The gray-market landscape for melanotan 2 underwent a qualitative shift beginning in approximately 2022, driven by TikTok content promoting nasal tanning sprays. Search volume for "nasal tanners" increased over 300% since spring 2024.^3,^4 TikTok has banned related hashtags (#melanotan, #melanotan2, #nasaltanningspray) and removed promotional content, but sellers adapt rapidly through euphemistic language and generic branding.^3

The Product Quality Issue

The most underappreciated risk of MT-II use is manufacturing-related, not pharmacological. When Imperial College London researchers analysed 10 commercially available tanning kits, some products contained more than 100 unidentified ingredients.^3,^4 LegitScript surveillance data indicate that 68% of adverse event reports associated with tanning peptides involved unlicensed vendors, and 41% of tested products showed laboratory-confirmed contamination or mislabelling.^4

Users cannot meaningfully assess their exposure. They may be injecting or inhaling degradation products, bacterial endotoxins, residual solvents, or entirely different peptide sequences alongside or instead of MT-II. For context on what proper peptide preparation involves, see the reconstitution guide. The BPC-157 guide covers the regulatory landscape and quality considerations in more detail.

The Youth Targeting Concern

The emergence of flavoured nasal tanning sprays — peach, bubblegum, grape — has raised alarm about youth targeting. The UK Chartered Trading Standards Institute has drawn explicit parallels to the disposable vape epidemic, warning that these products risk becoming consumer items among young people unfamiliar with melanocortin pharmacology or the consequences of non-selective receptor activation.^30

The FDA issued its first warning letter to Melanocorp in 2007 for marketing MT-II as a skin cancer preventative.^31 In the UK, nasal tanning sprays sold as "cosmetics" fall outside both medicinal products regulation and cosmetics regulation, creating an enforcement void that vendors actively exploit.^30 The TGA requested removal of 4,800+ unlawful therapeutic goods advertisements from digital platforms in 2023-2024, many related to melanotan.^32

MT-II is expected to remain restricted even following the February 2026 HHS partial reversal of Category 2 peptide bans, given its cardiovascular risk profile and melanoma signal.^33

The Emerging Melanocortin Frontier

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The melanocortin receptor system is experiencing a renaissance in drug development. Next-generation agents address the selectivity limitations that made MT-II unsuitable for clinical use — pursuing defined receptor targets through defined routes with characterised manufacturing standards. The trajectory is toward specificity, not potency.

Bivamelagon — Oral MC4R Agonism

Rhythm Pharmaceuticals in-licensed bivamelagon from LG Chem in January 2024 and reported positive Phase 2 results in July 2025 for acquired hypothalamic obesity.^34 The compound achieved BMI reductions of -9.3% (600 mg dose) and -7.7% (400 mg dose) versus a +2.2% increase in the placebo group at 14 weeks. As the first orally bioavailable MC4R agonist to demonstrate clinical efficacy, bivamelagon represents a structural advance in melanocortin therapeutics. Adverse events were mild: diarrhoea, nausea, and localised hyperpigmentation.^34

PL-8177 — Locally Acting Oral MC1R Agonism

Palatin Technologies' PL-8177 is a cyclic heptapeptide with sub-nanomolar MC1R affinity that, when administered orally, is not systemically absorbed — acting locally on intestinal MC1R to produce anti-inflammatory effects.^35 Phase 2 results in ulcerative colitis (March 2025) showed 78% clinical response versus 33% placebo, with 33% achieving clinical remission versus 0% placebo.^35 The sample size is extremely small (n=12), and these results require Phase 3 confirmation. No treatment-related side effects were reported.

Setmelanotide and Receptor-Selective Design

Setmelanotide (Imcivree), an MC4R-selective agonist with 20-fold selectivity over other melanocortin receptors (EC50: MC4R 0.27 nM vs MC1R 5.8 nM), received FDA approval for genetic obesity caused by POMC, PCSK1, or LEPR deficiency.^36 It embodies the selectivity paradigm that MT-II lacked — defined target, defined indication, characterised safety.

Neuroprotection and Expanding Indications

Preclinical research has identified MC4R agonists as neuroprotective agents in models of ischaemic stroke, traumatic brain injury, and Alzheimer's disease, acting through anti-inflammatory and anti-apoptotic pathways with a broad therapeutic time window.^37 Afamelanotide itself has entered a Phase IIa stroke trial, with early data (n=6) showing median NIHSS improvement from 6 to 2 by day 7.^38

The 2019 convergence — both Scenesse and Vyleesi approved in the same year — marked the moment the melanotan pharmacophore achieved clinical legitimacy through two separate regulatory pathways. The next phase of melanocortin therapeutics extends further: oral bioavailability, receptor-subtype selectivity, locally acting formulations, and indications spanning obesity, autoimmune inflammation, neurodegeneration, and skin repigmentation.

Risk-Benefit Assessment

Afamelanotide has established itself as a well-tolerated, effective MC1R agonist with a clean safety record spanning over a decade. Its limitation is narrow indication scope, though active Phase III trials in vitiligo and exploration in photodermatoses and stroke suggest the therapeutic surface is expanding. The melanoma safety question appears resolved for MC1R-selective activation: the compound is photoprotective, not oncogenic.

MT-II occupies a more complex position. Its pharmacological effects are real. The erectile response data from Wessells and colleagues remain among the most dramatic effect sizes in sexual medicine.^19 MT-II-driven melanogenesis reflects direct MC1R-mediated eumelanin synthesis without necessarily requiring UV-induced DNA damage. The appetite-suppressive effect, mediated centrally through MC4R, is measurable but subject to tachyphylaxis.

None of this changes the fundamental problem: MT-II was never designed for clinical use, was never subjected to the dose-ranging and safety protocols that regulatory approval demands, and is now distributed through channels where product quality is unverifiable. The serious adverse events — rhabdomyolysis, renal infarction, dysplastic nevi — occurred predominantly at supratherapeutic doses, but the absence of dosing guidance, quality assurance, or medical oversight makes such outcomes structurally predictable in the gray-market setting.

The social media amplification of nasal tanning sprays represents a genuine public health concern. The target demographic encounters a product of unknown composition through a route of unknown bioavailability, often combined with the UV exposure that constitutes the actual melanoma risk.

The lesson of MT-I versus MT-II is that receptor selectivity is not a pharmacological detail — it is the difference between a viable therapeutic and an uncontrollable polypharmacological agent. The next generation of melanocortin drugs embodies this lesson, pursuing defined targets through defined routes with defined manufacturing standards. For how receptor selectivity shapes protocol design more broadly, see the peptide stacking guide.

Frequently Asked Questions

References

^1 Langendonk JG et al. Afamelanotide for Erythropoietic Protoporphyria. NEJM 2015;373(1):48-59. PMID: 26132941

^2 Biolcati G et al. Long-term observational study of afamelanotide in 115 patients with EPP. Br J Dermatol 2015;172(6):1601-1612. PMID: 25494545

^3 LegitScript. Emerging Threat: Melanotan, Repackaging, and Online Sales. April 2024.

^4 Bohm M et al. An overview of benefits and risks of chronic MC1R activation. JEADV 2025;39:39-51. PMID: 39082868

^5 Sawyer TK et al. [Nle4, D-Phe7]-alpha-MSH: a highly potent alpha-melanotropin with ultralong biological activity. PNAS 1980;77(10):5754-5758. PMID: 6777774

^6 Mun Y, Kim W, Shin D. MC1R: Pharmacological and Therapeutic Aspects. Int J Mol Sci 2023;24(15):12152. PMID: 37569558

^7 Al-Obeidi F et al. Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin. J Med Chem 1989;32(12):2555-2561. PMID: 2555512

^8 Hruby VJ et al. Approaches to the rational design of selective melanocortin receptor antagonists. Expert Opin Drug Discov 2015;10(10):1057-1069. PMC4608743

^9 Minder EI et al. Pharmacokinetics and Pharmacodynamics of Afamelanotide. Clin Pharmacokinet 2017;56(8):815-823.

^10 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):1777-1784. PMID: 8637402

^11 FDA NDA 210797 — Scenesse clinical pharmacology review.

^12 King SH et al. Melanocortin receptors, melanotropic peptides and penile erection. Curr Top Med Chem 2007;7(11):1098-1106. PMID: 17584130

^13 Wensink D et al. Afamelanotide for prevention of phototoxicity in EPP. Expert Rev Clin Pharmacol 2021;14(2):151-160.

^14 FDA SCENESSE Label (revised August 2024).

^15 EMA EPAR: Scenesse.

^16 Lim HW et al. Afamelanotide and NB-UVB for Vitiligo. JAMA Dermatol 2015;151(1):42-50. PMID: 25230094

^17 CLINUVEL. Phase III vitiligo trial CUV105 recruits 200 patients. May 2025.

^18 Bremelanotide (Vyleesi). FDA approved 2019 for HSDD.

^19 Wessells H et al. Synthetic melanotropic peptide initiates erections in men with psychogenic ED. J Urol 1998;160(2):389-93. PMID: 9679884

^20 Wessells H et al. Melanocortin receptor agonists, penile erection, and sexual motivation. Int J Impot Res 2000;12(Suppl 4):S74-79. PMID: 11035391

^21 Wessells H et al. Effect of an alpha-MSH analog on penile erection in men with organic ED. Urology 2000;56(4):641-6. PMID: 11018622

^22 Intermittent MTII Application Evokes Repeated Anorexia and Robust Fat and Weight Loss. PMC2860181

^23 Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology 2014;228:34-6. PMID: 24355990

^24 Mahieu et al. Changes of melanocytic lesions induced by Melanotan injections and sun bed use in a teenage patient with FAMMM syndrome. Dermatol Pract Concept 2013;3(2):51-4. PMID: 23785612

^25 Eruptive dysplastic nevi following melanotan use. PMID: 22425244

^26 Habbema L et al. Risks of unregulated use of alpha-MSH analogues: a review. Int J Dermatol 2017;56(10):975-80. PMID: 28266027

^27 Dermoscopic changes in melanocytic nevi during use of melanotan II. PMID: 23052015

^28 Nelson ME et al. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol 2012;50(10):1169-73. PMID: 23121206

^29 Peters B et al. Melanotan II: a possible cause of renal infarction. CEN Case Rep 2020;9(2):159-61. PMID: 31953620

^30 UK CTSI. Nasal Tanning Sprays Linked with Skin Cancer and Serious Respiratory Problems. May 2025.

^31 FDA Warning Letter to Melanocorp. 2007.

^32 TGA. Don't risk using tanning products containing melanotan. January 2025.

^33 Frier Levitt. Regulatory Status of Peptide Compounding in 2025.

^34 Rhythm Pharmaceuticals. Bivamelagon Phase 2 results in acquired hypothalamic obesity. July 2025.

^35 Palatin Technologies. PL8177 Phase 2 topline results in UC. March 2025.

^36 Setmelanotide — NCBI Bookshelf / StatPearls. NBK589641

^37 Giuliani et al. Multiple beneficial effects of MC4R agonists in experimental neurodegenerative disorders. PMID: 27916623

^38 Stanislaus V et al. A feasibility and safety study of afamelanotide in acute stroke patients. BMC Neurol 2023;23(1):281.