Cyclic heptapeptide α-MSH analogue (broad melanocortin receptor agonist)
Melanotan II
Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-NH2 — a synthetic cyclic heptapeptide α-MSH analogue with a C-terminal amide, broadly active across MC1R, MC3R, MC4R and MC5R
Overview
Melanotan II is the historical parent of an entire branch of approved-product peptide pharmacology, and it has never itself been approved by any regulator. That paradox is the central editorial fact about the compound. In the 1980s and 1990s the Hruby and Levine groups at the University of Arizona developed a series of α-MSH analogues to study melanocortin receptor pharmacology. Melanotan II — a cyclic heptapeptide with an acetylated N-terminus, a D-phenylalanine substitution, and a C-terminal amide — became a foundational research tool because it activates all four peripheral melanocortin receptors (MC1R, MC3R, MC4R, MC5R) with high potency and much greater stability than native α-MSH. That broad pharmacology is what makes it interesting scientifically and what makes it problematic clinically.
The clinical trajectory began with an accidental observation. In early human tanning studies of Melanotan II at the University of Arizona, investigators noticed that male participants developed spontaneous erections. That single observation reframed the compound's future. Palatin Technologies licensed a modified version of the molecule (bremelanotide, PT-141 — differing from Melanotan II only in the C-terminal chemistry) and developed it into an FDA-approved treatment for HSDD in premenopausal women (Vyleesi, 2019-06-21). Clinuvel Pharmaceuticals took a different α-MSH analogue (afamelanotide — Melanotan I — differing more substantially in structure) into an FDA and EMA approval for erythropoietic protoporphyria (Scenesse, EMA 2014, FDA 2019-10-08). Melanotan II itself — the original — was not carried forward as a pharmaceutical product by any sponsor.
The regulatory position today is unambiguous. Melanotan II is not approved anywhere. Multiple national medicines regulators — the UK MHRA, the Norwegian Medicines Agency, the Irish HPRA, and the Australian TGA — have issued specific warnings against grey-market Melanotan products, citing unauthorised-medicine status and safety concerns. The compound circulates as a lyophilized peptide sold through research-supply channels for cosmetic tanning and sexual-response effects, and consumer discussions frequently blur the distinction between it and the approved products it inspired.
The safety picture matters because the compound's pharmacology touches many organ systems. Its broad melanocortin activity produces the sought-after skin darkening (via MC1R) and sexual-response effects (via MC4R), but also the characteristic acute nausea and flushing, appetite suppression, blood-pressure effect, and — importantly — melanocyte activation that can change the appearance of pre-existing moles. Case reports document melanoma diagnoses following naevus darkening during Melanotan II use, as well as episodes of rhabdomyolysis and priapism. None of these are 'proof' that the compound causes those outcomes at scale, but they establish a specific safety profile that any responsible page has to name.
Quick Facts & Evidence
- Category
- Cyclic heptapeptide α-MSH analogue (broad melanocortin receptor agonist)
- Research area
- Melanocortin peptide
- Most studied for
- Melanocortin receptor pharmacology (historical research tool)
- Skin darkening (cosmetic grey-market use — not an approved use)
- Sexual arousal / erectile response (the observation that led to bremelanotide)
- Appetite suppression (broader MC4R activation)
- Clinical status
- Research use only — no approved clinical indication
- Human evidence
- Preclinical Evidence
- Regulatory status
- Multiple national regulators (Norway, Ireland, Australia) have issued warnings against grey-market cosmetic use of Melanotan II. The compound has no approved product identity anywhere.
Preclinical Evidence
Data are from animal models, cell studies, or anecdotal community reports. No controlled human evidence.
Research Protocols
Research Protocol Snapshot
Preparation covered on this page
Freeze-dried injectable research format
This page covers the RUO lyophilized Melanotan II vial reconstituted with bacteriostatic water for subcutaneous research use, following the standard Healthy Mango preparation convention. Melanotan II itself has never been approved by any regulator; the approved products in the melanocortin space (Scenesse for afamelanotide/Melanotan I; Vyleesi for bremelanotide/PT-141) are different molecules with different regulatory identities.
Melanotan II research values at a glance.
| Item | Example value |
|---|---|
| Vial size | 10 mg |
| Liquid used to mix | Bacteriostatic water |
| Amount of liquid added | 2.0 mL |
| Final concentration | 5 mg/mL |
| How it's given | Subcutaneous injection |
| Starting dose | 0.25 mg (test for nausea; inject at night) |
| Maintenance dose | 0.5 mg once tolerance is established |
| Frequency | Daily during loading; 2–3× per week for maintenance |
| UV exposure | Required — same as Melanotan I; without UV substrate the tanning effect does not build |
Reported Dosing
The practitioner-reference research protocol for Melanotan II is 0.25 mg starting (to test for nausea, injected at night), stepping up to 0.5 mg once tolerance is established. Daily during loading, 2–3 times per week for maintenance. UV exposure is required for the tanning effect. It is educational reference, not a recommendation.
The Reported Protocol
| Dose | Frequency | Duration | Notes |
|---|---|---|---|
| 0.25 mg | Daily, subcutaneous, at night | Starting / tolerance test | 0.05 mL at 5 mg/mL; nausea peaks 30–90 min post-injection |
| 0.5 mg | Daily during loading, then 2–3× per week | Loading until colour established, then maintenance | 0.10 mL at 5 mg/mL |
Why protocols vary
Melanotan II activates all four peripheral melanocortin receptors (MC1R, MC3R, MC4R, MC5R). MC1R drives the tanning effect (like Melanotan I), MC3R drives appetite suppression, MC4R drives sexual arousal, MC5R has less-characterised effects. Broader receptor coverage explains faster and stronger tanning than Melanotan I — and also the extra side effects.
Starting at 0.25 mg at night is a tolerance strategy — nausea peaks 30–90 minutes post-injection, and sleeping through that window avoids most of the discomfort. Only once tolerance is established does the maintenance dose of 0.5 mg apply.
The daily-loading-then-2-3x/week-maintenance cadence matches the MC1R-driven melanin build-up; it is the same two-phase pattern as Melanotan I, adjusted to the higher receptor coverage.
Preparing the Solution
Turning the freeze-dried powder into a measurable liquid.
Documented preparation
The documented research protocol is based on this preparation concentration.
Freeze-dried powder: 10 mg vial
Diluent: 2.0 mL bacteriostatic water
Final concentration: 5 mg/mL
Vial and volume from the practitioner reference; concentration calculated · Research-practitioner guide
Your vial
Matching preparation
Bacteriostatic water
2mL
Resulting concentration
5 mg/mL
Equivalent volume
The reported research amount of 0.25–0.5 mg is contained within
0.05–0.10mL
of the prepared solution now in your vial.
Show calculation
- Documented concentration
- 10 mg ÷ 2 mL = 5 mg/mL
- Bacteriostatic water to match the documented concentration
- 10 mg ÷ 5 mg/mL = 2 mL
- Equivalent volume at this concentration
- 0.25–0.5 mg ÷ 5 mg/mL = 0.05–0.1 mL
This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.
This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.Sources for these values
- Documented in the practitioner referenceResearch-practitioner guide
This example explains how concentration and volume are calculated for the standard RUO preparation. It is not a preparation guide.
How It's Given
Method used for this format
Subcutaneous injection, daily during loading (at night) then 2–3× weekly for maintenance
Documented in the practitioner reference · Research-practitioner guide
Why this method
Melanotan II is a cyclic heptapeptide analogue of α-MSH; the subcutaneous route delivers it into circulation without the gastrointestinal degradation that would break the molecule down.
Systemic subcutaneous dosing is used because melanocortin receptor activation must reach melanocytes and other tissues throughout the body, not just a localised depot.
Injecting at night keeps the nausea window aligned with sleep during loading.
Injection sites reported
- Abdomen (rotate sites)
- Front of the thigh
- Avoid scarred, bruised, inflamed, or infected skin
Storage
Before mixing
- Refrigerate 2–8 °C
- Protect from light
- Do not freeze
General RUO practice · Research-practitioner guide
After mixing
- Refrigerate 2–8 °C
- Use within 7–10 days
- Do not freeze
- Discard if cloudy or discoloured
General RUO practice · Research-practitioner guide
Handling
- Direct diluent slowly down the vial wall
- Gently swirl until dissolved — do not shake
- New sterile needle each draw
- Do not share vials
General RUO practice · Research-practitioner guide
Storage guidance summarises standard RUO peptide handling. Melanotan II itself is not an approved product anywhere; Scenesse (afamelanotide/Melanotan I) and Vyleesi (bremelanotide/PT-141) are different molecules and their labelled storage instructions do not apply here.
Common Cycle
The practitioner reference frames Melanotan II as a two-phase pattern — daily loading until colour is established, then 2–3×/week maintenance.
- Cycle Length
- Loading (variable) + maintenance until desired result is maintained
- Break Before the Next Cycle
- No calendar-fixed cycle; goal-driven
- What the Research Shows
- No approved indication; no post-marketing surveillance framework applies to Melanotan II itself
Documented in the practitioner reference · Research-practitioner guide
Melanotan compounds darken existing moles; any personal or family history of melanoma is an absolute contraindication in the practitioner reference. Case reports of rhabdomyolysis have been published for Melanotan II specifically (Hoyle 2018) — an added risk not present with Melanotan I.
Compound Overview
Current areas of research
Effects reported in grey-market use and small pharmacological studies. There is no approved-use benefit list because there is no approved use.
- Skin darkening via MC1R-driven eumelanin synthesis
- Sexual-response effects — the accidental clinical observation that reframed the compound's development and led to bremelanotide
- Appetite suppression — a downstream consequence of broader MC4R activation
- Acute rapid onset — practitioners report perceptible effects within 30–60 minutes of dosing
Mechanism of action
Melanotan II is the historical parent of an entire branch of approved-product peptide pharmacology, and it has never itself been approved by any regulator. That paradox is the central editorial fact about the compound. In the 1980s and 1990s the Hruby and Levine groups at the University of Arizona developed a series of α-MSH analogues to study melanocortin receptor pharmacology. Melanotan II — a cyclic heptapeptide with an acetylated N-terminus, a D-phenylalanine substitution, and a C-terminal amide — became a foundational research tool because it activates all four peripheral melanocortin receptors (MC1R, MC3R, MC4R, MC5R) with high potency and much greater stability than native α-MSH. That broad pharmacology is what makes it interesting scientifically and what makes it problematic clinically.
The clinical trajectory began with an accidental observation. In early human tanning studies of Melanotan II at the University of Arizona, investigators noticed that male participants developed spontaneous erections. That single observation reframed the compound's future. Palatin Technologies licensed a modified version of the molecule (bremelanotide, PT-141 — differing from Melanotan II only in the C-terminal chemistry) and developed it into an FDA-approved treatment for HSDD in premenopausal women (Vyleesi, 2019-06-21). Clinuvel Pharmaceuticals took a different α-MSH analogue (afamelanotide — Melanotan I — differing more substantially in structure) into an FDA and EMA approval for erythropoietic protoporphyria (Scenesse, EMA 2014, FDA 2019-10-08). Melanotan II itself — the original — was not carried forward as a pharmaceutical product by any sponsor.
The regulatory position today is unambiguous. Melanotan II is not approved anywhere. Multiple national medicines regulators — the UK MHRA, the Norwegian Medicines Agency, the Irish HPRA, and the Australian TGA — have issued specific warnings against grey-market Melanotan products, citing unauthorised-medicine status and safety concerns. The compound circulates as a lyophilized peptide sold through research-supply channels for cosmetic tanning and sexual-response effects, and consumer discussions frequently blur the distinction between it and the approved products it inspired.
The safety picture matters because the compound's pharmacology touches many organ systems. Its broad melanocortin activity produces the sought-after skin darkening (via MC1R) and sexual-response effects (via MC4R), but also the characteristic acute nausea and flushing, appetite suppression, blood-pressure effect, and — importantly — melanocyte activation that can change the appearance of pre-existing moles. Case reports document melanoma diagnoses following naevus darkening during Melanotan II use, as well as episodes of rhabdomyolysis and priapism. None of these are 'proof' that the compound causes those outcomes at scale, but they establish a specific safety profile that any responsible page has to name.
- Cyclic heptapeptide α-MSH analogue with broad activity across MC1R, MC3R, MC4R and MC5R — the pharmacology that led to bremelanotide (Vyleesi) and inspired afamelanotide (Scenesse)
- Never approved by any regulator; multiple national medicines authorities have issued specific warnings against grey-market cosmetic use
- Case reports link Melanotan II use with melanocytic naevus darkening and subsequent melanoma diagnoses, priapism, and rhabdomyolysis
Human research
The foundational pharmacological characterisation of Melanotan II was published by the Dorr, Hadley and Hruby groups at the University of Arizona through the 1990s (Dorr et al. Life Sciences 1996 is the reference frequently cited for early tanning-effect confirmation). Those studies characterised the potent broad-spectrum melanocortin receptor activity of the compound and established the amino-acid sequence and cyclisation strategy that later drug programmes built on.
The clinical human evidence base for Melanotan II proper is small. There are no phase-3 randomised trials. The clinical data that exist are from small pharmacology studies and clinician-authored case reports. The safety literature is where the picture is most substantive: multiple case reports document rhabdomyolysis (Hoyle et al. 2018 is one representative example), priapism, systemic reactions, and — most concerning — melanoma diagnoses following naevus change during Melanotan II use (Cardones et al. 2009 and follow-up literature).
The Hadley and Hruby melanocortin review (2004) is a good framework document for readers who want to understand the compound's place in the broader melanocortin receptor pharmacology tradition, and how its receptor-broad activity contrasts with the more MC1R-selective afamelanotide and the more MC4R-selective bremelanotide.
Dorr et al. 1996 (Life Sciences)
Early clinical characterisation of Melanotan II tanning effects at the University of Arizona. One of the foundational human pharmacology reports on the compound. Small, uncontrolled by modern standards but historically important.
Hadley & Hruby 2004 (melanocortin review)
Consolidating review of the melanocortin receptor pharmacology tradition, with Melanotan II situated as the broad-agonist parent of the more selective molecules that later reached approved-product status.
Cardones et al. 2009 (melanoma after Melanotan II)
Case report of a melanoma diagnosed after conspicuous darkening of a pre-existing naevus in a patient using Melanotan II. One of the sentinel reports raising the naevus-surveillance concern that applies more broadly to the melanocortin peptide class.
Hoyle et al. 2018 (rhabdomyolysis)
Case report of rhabdomyolysis in a young user of grey-market Melanotan II. Representative of the broader case-report literature on systemic adverse events with the compound.
MHRA Melanotan warning
UK Medicines and Healthcare Products Regulatory Agency public warning about Melanotan I and II as unauthorised medicines sold as cosmetic tanning agents. The regulatory framing that gets omitted from most grey-market marketing.
Melanotan II has never been an approved medicinal product. Its historical importance is scientific — the observation of accidental sexual-response effects in tanning studies of the compound at the University of Arizona is the reason bremelanotide became a drug. Its consumer identity today is a grey-market cosmetic peptide, and multiple national medicines regulators have issued explicit warnings about that use.
The compound is on the WADA prohibited list in some interpretations under the S0 category (non-approved substances) when used for its intended purpose, though it is not listed as a specifically prohibited peptide by name. Competitive athletes should verify current WADA status.
There is no active pharmaceutical development program to bring Melanotan II itself to market. The commercial and regulatory attention to the melanocortin family has flowed to its structural relatives (afamelanotide and bremelanotide), both of which are approved products with narrow indications and specific safety monitoring frameworks that grey-market Melanotan II does not carry.
Safety considerations
Adverse events reported in grey-market use, small clinical studies, and published case reports.
- Acute nausea, flushing, yawning
- Injection-site reactions
- Facial and neck darkening beyond the intended cosmetic target
- Spontaneous erection / priapism (case reports)
- Melanocytic naevus darkening — case reports document subsequent melanoma diagnoses
- Rhabdomyolysis (case reports)
- Blood-pressure elevation and cardiovascular events (case reports)
- Appetite suppression — considered by users but a real physiological effect
There is no approved-label list because there is no approved use. The considerations below draw on the compound's pharmacology and case-report safety literature.
- Any history of melanoma or non-melanoma skin cancer — do not use
- Uncontrolled hypertension or cardiovascular disease — do not use
- Pregnancy and breastfeeding — no human safety data
- New or changing pigmented lesions during use warrant urgent dermatological assessment
- The compound has been the subject of MHRA and other regulator warnings; grey-market provenance is not equivalent to an approved product
- Do not conflate Melanotan II with Scenesse (afamelanotide) or Vyleesi (bremelanotide) — different molecules, different regulatory identities
Monitoring
- Full-skin dermatological examination before, during, and after use
- Blood pressure
- Any change in mole appearance during use
- Systemic symptoms after injection
Frequently asked questions
Is Melanotan II the same as PT-141 (bremelanotide)?
No — they are structurally related but not identical. Melanotan II is Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-NH2 (C-terminal amide). Bremelanotide is Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH (free C-terminal acid). The single-atom change substantially alters receptor selectivity: Melanotan II is broadly active across MC1R, MC3R, MC4R and MC5R; bremelanotide is more MC4R-selective. Only bremelanotide has an approved product identity (Vyleesi in HSDD). Consumer discussions that equate the two are inaccurate.
Is Melanotan II the same as Melanotan I (afamelanotide)?
No. Melanotan I is a linear tridecapeptide α-MSH analogue with Nle4 and D-Phe7 substitutions — it retains more α-MSH-like structure and is more MC1R-selective in relative terms. Melanotan II is a cyclic heptapeptide with broader receptor coverage. Melanotan I (as afamelanotide/Scenesse) is an approved product for EPP; Melanotan II is not approved anywhere.
Why isn't Melanotan II approved for cosmetic tanning?
Two reasons. First, the compound's pharmacology is broad — cosmetic pigmentation is one effect, but sexual-response effects, appetite suppression, cardiovascular effects and naevus activation are all inherent to its receptor coverage. That is not a favourable profile for a cosmetic-use approval. Second, no pharmaceutical sponsor has pursued the compound as a drug. The commercial attention to melanocortin peptides has gone to more selective structural relatives (afamelanotide and bremelanotide) for defined medical indications where the risk/benefit is different. The UK MHRA, Norwegian, Irish and Australian regulators have specifically warned against the grey-market use.
What is the naevus (mole) concern?
Melanotan II activates MC1R on melanocytes, and pre-existing melanocytic naevi can darken conspicuously during use. Case reports have documented melanoma diagnoses following naevus change under Melanotan II use (Cardones 2009 and follow-up literature). That does not prove the compound causes melanoma at scale — case reports do not — but it establishes a specific reason for baseline and periodic dermatological examination and for immediate assessment of any changing mole. This concern also applies to the more selective approved products (Scenesse, Vyleesi), which is why their labels contain naevus-monitoring language.
What are the rhabdomyolysis and priapism reports about?
Rhabdomyolysis (muscle breakdown releasing myoglobin into the bloodstream) and priapism (sustained painful erection) have been documented in case reports of Melanotan II users. Neither is a common outcome; both are documented adverse events specific to the compound. They are consistent with the compound's broad melanocortin activation. The consumer-facing sources that promote Melanotan II typically omit these reports — a page that represents the primary literature has to name them.
References
- [1]
Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study — Dorr RT, Lines R, Levine N, et al., Life Sciences (1996)
- [2]
Discovery and development of novel melanogenic drugs — the Melanotan I and Melanotan II peptides in the context of melanocortin receptor pharmacology — Hadley ME, Hruby VJ, Pigment Cell Research (chapter / review) (2004)
- [3]
MHRA public warning about Melanotan I and Melanotan II products — unauthorised medicines sold as cosmetic tanning agents — UK Medicines and Healthcare Products Regulatory Agency (MHRA), MHRA public statement (2018)
https://www.gov.uk/government/news/mhra-warning-on-melanotan-injections
- [4]
α-Melanocyte-stimulating hormone-related peptides — dysplastic naevus and melanoma reports following Melanotan II use — Cardones AR, Grichnik JM, Archives of Dermatology (2009)
- [5]
Rhabdomyolysis in a young adult using unauthorised Melanotan II for cosmetic tanning — a case report — Hoyle CH, Sun A, Clemens ML, et al., BMJ Case Reports (representative case report) (2018)
- [6]
Peptides & Compounds — The No-Jargon Guide (v5) — Healthy Mango Editorial, Healthy Mango practitioner reference (2026)
Laboratory Reference Notice
This section summarizes procedures and study parameters reported in published scientific literature and laboratory protocols. It is provided for educational and research reference only and must not be interpreted as medical advice, clinical guidance, or instructions for personal use.
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