Melanotan-II (MT-II)
What happens when an analogue activates a whole family of receptors instead of one? Melanotan-II illustrates precisely the consequences of low pharmacological selectivity.
- Research Use Only
- Molecule under study
- Living document
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- Current research state
- Unapproved molecule. Used in preclinical research; the origin of bremelanotide (PT-141). PHL presents it as Research Use Only.
- Current clinical phase
- Preclinical and exploratory research — no marketing authorization
- Last update
- 21 July 2026 · Reference fact sheet v1.0
- Living document
- Updated regularly as research progresses.
What is Melanotan-II (MT-II)?
Melanotan-II, or MT-II, is a synthetic cyclic heptapeptide developed at the University of Arizona in the 1980s, building on research into α-MSH.
Its cyclic structure gives it greater stability and higher biological activity than natural α-MSH.
Originally designed for photoprotection, it was soon found to act on other melanocortin pathways (sexual desire, appetite) — which led to the development of bremelanotide, its derivative focused on sexual desire.
Names you may come across
This molecule is mainly designated under the following names in the literature.
Original research name.
A common abbreviation in the literature.
Understanding it simply
Three simple reference points for understanding Melanotan-II.
A broader-acting cousin of MT-1
Unlike Melanotan-I, it acts on several melanocortin receptors — hence its effects on pigmentation, libido, and appetite.
The origin of a medicine
Bremelanotide (Vyleesi®), derived from MT-II, is approved for female sexual desire. Scenesse® (afamelanotide), often mentioned alongside it, is a distinct molecule designed before it.
No approval
MT-II is not approved by any agency. Its safety profile during chronic use is poorly documented.
What research shows today
Science advances step by step. We clearly distinguish what is firmly established from what remains under study.
- A cyclic heptapeptide with the structure Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-NH2, an α-MSH analogue. — established
- A non-selective agonist of melanocortin receptors (MC1R, MC3R, MC4R, MC5R). — established
- Stimulates melanogenesis via MC1R — systemic skin pigmentation. — established
- Reported effects on libido (via central MC4R) and appetite (via hypothalamic MC4R). — established
- Precursor of bremelanotide (Vyleesi®, PT-141), its deamidated metabolite; afamelanotide (Scenesse®, MT-1) is a distinct linear analogue designed before MT-II. — established
- Long-term effects and the safety profile during chronic use are poorly documented in supervised clinical trials. — ongoing
Well-characterized melanocortin pharmacology and older preliminary clinical data; the molecule is not approved. Bremelanotide (PT-141), approved for a different indication, derives from MT-II; afamelanotide (MT-1) is a distinct analogue designed earlier.
What the research shows
- Comprehensive, well-characterized melanocortin pharmacology.
- Demonstrated induction of melanogenesis through MC1R activation.
- Central effects on libido (via MC4R) documented in preclinical models and confirmed through the clinical development of bremelanotide.
- Effects on appetite via hypothalamic MC4R — a pathway used in pharmaceutical development for obesity (setmelanotide).
What still remains to be studied
- Safety during chronic use — dermatological monitoring is important (skin darkening, ephelides, pigmented lesions).
- Isolated case reports of melanoma in users — no proof of causation, but monitoring is recommended.
- Pharmacokinetics and pharmacodynamics during prolonged use are poorly characterized.
What we know today
Not all information carries the same weight of evidence. We therefore present it across three clearly distinct levels, from the most solid to the most indicative.
What scientific publications show
Scientific evidence- MT-II provided the molecular scaffold of bremelanotide; afamelanotide, from the same laboratory, is independent of it.
- Publications consistently describe its non-selective melanocortin mechanism.
- Long-term tolerability data are limited because clinical development was not continued.
What some professionals report
Documented- Dermatologists emphasize that induced pigmentation does not replace conventional photoprotection.
- Monitoring of pigmented lesions is recommended in cases of prolonged exposure.
What the community reports
Field observations- Community reports describe rapid tanning, reduced appetite, and increased libido.
- These individual observations do not replace clinical data or medical advice.
The level of evidence is intermediate: solid pharmacology, but few supervised clinical trials of MT-II itself — most clinical data concern its derivatives.
How does Melanotan-II (MT-II) work?
Melanotan-II activates several melanocortin receptors, explaining the diversity of its reported effects.
- MC1R receptor (melanocytes)
- Activation of eumelanin synthesis — skin pigmentation.
- MC4R receptor (hypothalamus)
- Modulation of sexual desire (limbic circuits) and energy balance (satiety, appetite).
- MC3R receptor
- A complex role in energy homeostasis and inflammation.
- MC5R receptor
- Expressed notably in sebaceous glands — its physiological role remains debated.
This lack of selectivity explains both the wide range of observed effects and the subsequent shift in pharmaceutical development toward more targeted molecules.
Clinical trials timeline
A molecule under study progresses step by step. Here, simply, is where the research currently stands.
- Discovery· 1980sCompleted
Synthesis at the University of Arizona
Hruby and Hadley develop a cyclic α-MSH analogue with improved stability and affinity.
- Preclinical· 1990sCompleted
Multi-receptor characterization
Demonstration of activity at MC1R, MC3R, MC4R, and MC5R, and of effects on pigmentation, sexual function, and appetite.
- Repurposing· 1990s-2000sCompleted
Development of bremelanotide
Palatin Technologies develops bremelanotide (PT-141), an active metabolite of MT-II, for sexual desire. In parallel, Clinuvel develops afamelanotide (MT-1), a linear analogue designed before MT-II.
- Approval· 2014-2019Completed
Approvals of related molecules (Scenesse®, Vyleesi®)
Afamelanotide (EMA 2014, FDA 2019) and bremelanotide, derived from MT-II (FDA 2019), obtain their approvals.
- Current status· TodayOngoing
Research only
MT-II itself remains unapproved; it is used in research and as a reference in pharmacology.
Available analyses
No analytical document has been published for this molecule to date.
Open the analysis libraryFrequently asked questions
Is Melanotan-II an approved medicine?
Established: no. MT-II itself is not approved by any agency. Its derivative bremelanotide (Vyleesi®) is approved for female sexual desire; afamelanotide (Scenesse®), approved for EPP, is a distinct analogue.
How does it differ from Melanotan-I?
Established: MT-I (afamelanotide) is a linear peptide with 13 amino acids, more selective for MC1R (pigmentation). MT-II is a shorter, non-selective cyclic peptide with additional effects on libido and appetite.
Can it replace sun protection?
Established: no. The induced pigmentation does not replace conventional photoprotection measures.
What adverse effects have been reported?
Established: nausea (common), flushing, spontaneous erections, generalized skin darkening, the appearance of ephelides and pigmented spots, and injection-site reactions.
Is there a risk of melanoma?
Further study needed: a few case reports have been published, with no established proof of causation. Dermatological monitoring remains recommended.
Why has MT-II never been approved?
To be studied: not all reasons are public. Development shifted to bremelanotide, a derivative of MT-II, for a specific indication; MT-II itself has not been the subject of any known approval application.
Scientific publications
Selected reference publications on Melanotan-II — melanocortin pharmacology and historical clinical reports. An evolving bibliography.
Discovery and development of novel melanogenic drugs. Melanotan-I and -II
Hadley M. E., Hruby V. J. et al. · Pharmaceutical Biotechnology · 1987
Melanotan-II induced eruptive melanocytic naevi and drug-induced hyperpigmentation
Cardinali G. et al. · Journal of the European Academy of Dermatology and Venereology · 2011
Glossary
- α-MSH
- α-Melanocyte Stimulating Hormone — a naturally occurring hormone derived from POMC and an agonist of melanocortin receptors.
- Melanocortin receptors (MCR)
- A family of 5 receptors (MC1R–MC5R) involved in pigmentation, energy balance, sexuality, and inflammation.
- MC1R
- A receptor expressed on melanocytes, the main regulator of eumelanin synthesis.
- MC4R
- A central receptor, mainly hypothalamic, involved in sexual desire and appetite.
- Eumelanin
- A brown/black skin pigment with photoprotective properties.
- Ephelides
- Small pigmented skin spots (freckles) that may appear under melanocortin stimulation.
Continue your discovery
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Reference fact sheet — version 1.0, updated on 21 July 2026. The full regulatory and scientific framework is gathered in the “Important information” box at the top of the fact sheet.