Melanotan 1

Key Benefits#

• Induces skin pigmentation/tanning without UV exposure
• Provides photoprotection in photosensitivity conditions (EPP)
• FDA-approved for erythropoietic protoporphyria (SCENESSE)
• Approved in EU for EPP treatment
• Anti-inflammatory via MC1R
• Mild libido enhancement
• Potential skin cancer prevention through melanin protection

Mechanism of Action#

Melanotan 1 is a superpotent analog of α-MSH with substitutions [Nle4, D-Phe7] that increase receptor binding affinity and metabolic stability. It selectively activates MC1R on melanocytes, stimulating tyrosinase activity and melanin synthesis (eumelanin — the brown/black protective form). Unlike natural tanning which requires UV damage, MT-1 triggers melanogenesis without UV radiation. MT-1 also has anti-inflammatory, photoprotective, and mild libido-enhancing effects via MC1R and central MC3R/MC4R.

Dosing Protocols#

Side Effects#

• Nausea (especially at higher doses)
• Facial flushing
• Fatigue
• Injection site reactions
• Darkening of moles and freckles
• Rare: spontaneous erection (less than MT-II)
• Hyperpigmentation in unwanted areas

Contraindications#

Monitor moles regularly during use (melanogenesis may reveal pre-existing nevi). Personal or family history of melanoma requires caution. Not for use in pregnancy. Avoid excessive UV exposure during use.

Storage#

Store lyophilized at -20°C. Reconstituted: 4°C, use within 30 days. Protect from light (photosensitive compound).

Featured In Stacks#

1. 1.
   Investigation of the stability profile of therapeutic α-MSH analogue: Insights from liquid chromatography-high resolution mass spectrometry analysis of afamelanotide

   Chawathe A, Sharma N · Journal of pharmaceutical and biomedical analysis · 2026PubMed Verified

2. 2.
   Melanocortin Receptor Agonist Bremelanotide Induces Cell Death and Growth Inhibition in Glioblastoma Cells via Suppression of Survivin Expression

   Suzuki S, Kitanaka C, Okada M · Anticancer research · 2024PubMed Verified

3. 3.
   Melanocortin-receptor 4 activation modulates proliferation and differentiation of rat postnatal hippocampal neural precursor cells

   Carniglia L, Turati J, Saba J, López Couselo F, Romero AC, Caruso C et al. · Neuropharmacology · 2024PubMed Verified

4. 4.
   Polysorbate 80 coated chitosan nanoparticles for delivery of α-melanocyte stimulating hormone analog (NDP-MSH) to the brain reverse cognitive impairment related to neuroinflammation produced by a high-fat diet (HFD)

   Herrera G, Scimonelli T, Lasaga M, Granero G, Onnainty R · Neuropharmacology · 2024PubMed Verified

5. 5.
   Melanocortin receptor agonist NDP-α-MSH improves cognitive deficits and microgliosis but not amyloidosis in advanced stages of AD progression in 5XFAD and 3xTg mice

   Daini E, Vandini E, Bodria M, Liao W, Baraldi C, Secco V et al. · Frontiers in immunology · 2022PubMed Verified

6. 6.
   Structures of active melanocortin-4 receptor-Gs-protein complexes with NDP-α-MSH and setmelanotide

   Heyder NA, Kleinau G, Speck D, Schmidt A, Paisdzior S, Szczepek M et al. · Cell research · 2021PubMed Verified

7. 7.
   NDP-MSH treatment recovers marginal lungs during ex vivo lung perfusion (EVLP)

   Lonati C, Battistin M, Dondossola DE, Bassani GA, Brambilla D, Merighi R et al. · Peptides · 2021PubMed Verified

8. 8.
   Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice

   Fu S, Luo X, Wu X, Zhang T, Gu L, Wang Y et al. · Oxidative medicine and cellular longevity · 2020PubMed Verified

9. 9.
   Melanocortin therapy ameliorates podocytopathy and proteinuria in experimental focal segmental glomerulosclerosis involving a podocyte specific non-MC1R-mediated melanocortinergic signaling

   Qiao Y, Wang P, Chang M, Chen B, Ge Y, Malhotra DK et al. · Clinical science (London, England : 1979) · 2020PubMed Verified

10. 10.
    NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB/Nr4a1/NF-κB pathway after intracerebral hemorrhage in mice

    Wu X, Fu S, Liu Y, Luo H, Li F, Wang Y et al. · Journal of neuroinflammation · 2019PubMed Verified

11. 11.
    A tumor-targeted immune checkpoint blocker

    Zhang Y, Fang C, Wang RE, Wang Y, Guo H, Guo C et al. · Proceedings of the National Academy of Sciences of the United States of America · 2019PubMed Verified

12. 12.
    NDP-MSH reduces oxidative damage induced by palmitic acid in primary astrocytes

    Ramírez D, Saba J, Turati J, Carniglia L, Imsen M, Mohn C et al. · Journal of neuroendocrinology · 2019PubMed Verified

13. 13.
    A glimpse into the underground market of melanotan

    Callaghan Iii DJ · Dermatology online journal · 2018PubMed Verified

14. 14.
    Design of MC1R Selective γ-MSH Analogues with Canonical Amino Acids Leads to Potency and Pigmentation

    Zhou Y, Mowlazadeh Haghighi S, Zoi I, Sawyer JR, Hruby VJ, Cai M · Journal of medicinal chemistry · 2017PubMed Verified

15. 15.
    Key amino acid residue in Melanocortin-1 receptor (melanocyte α-MSH receptor) for ligand selectivity

    Yang Y, Chen M, Ventro G, Harmon CM · Molecular and cellular endocrinology · 2017PubMed Verified

16. 16.
    Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review

    Habbema L, Halk AB, Neumann M, Bergman W · International journal of dermatology · 2017ReviewPubMed Verified

17. 17.
    Effects of melanocortin-4 receptor agonists and antagonists on expression of genes related to reproduction in spotted scat, Scatophagus argus

    Jiang DN, Li JT, Tao YX, Chen HP, Deng SP, Zhu CH et al. · Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2017PubMed Verified

18. 18.
    A Macrocyclic Agouti-Related Protein/[Nle(4),DPhe(7)]α-Melanocyte Stimulating Hormone Chimeric Scaffold Produces Subnanomolar Melanocortin Receptor Ligands

    Ericson MD, Freeman KT, Schnell SM, Haskell-Luevano C · Journal of medicinal chemistry · 2017PubMed Verified

19. 19.
    Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

    Mykicki N, Herrmann AM, Schwab N, Deenen R, Sparwasser T, Limmer A et al. · Science translational medicine · 2016PubMed Verified

20. 20.
    [Nle4, D-Phe7]-α-MSH Inhibits Toll-Like Receptor (TLR)2- and TLR4-Induced Microglial Activation and Promotes a M2-Like Phenotype

    Carniglia L, Ramírez D, Durand D, Saba J, Caruso C, Lasaga M · PloS one · 2016PubMed Verified

21. 21.
    Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors

    Todorovic A, Ericson MD, Palusak RD, Sorensen NB, Wood MS, Xiang Z et al. · ACS chemical neuroscience · 2016PubMed Verified

22. 22.
    Molecular cloning, tissue distribution, and pharmacological characterization of melanocortin-4 receptor in spotted scat, Scatophagus argus

    Li JT, Yang Z, Chen HP, Zhu CH, Deng SP, Li GL et al. · General and comparative endocrinology · 2016PubMed Verified

23. 23.
    NDP-α-MSH attenuates heart and liver responses to myocardial reperfusion via the vagus nerve and JAK/ERK/STAT signaling

    Ottani A, Giuliani D, Neri L, Calevro A, Canalini F, Vandini E et al. · European journal of pharmacology · 2015PubMed Verified

24. 24.
    α-Melanocyte-stimulating-hormone (α-MSH) modulates human chondrocyte activation induced by proinflammatory cytokines

    Capsoni F, Ongari AM, Lonati C, Accetta R, Gatti S, Catania A · BMC musculoskeletal disorders · 2015PubMed Verified

25. 25.
    NDP-α-MSH induces intense neurogenesis and cognitive recovery in Alzheimer transgenic mice through activation of melanocortin MC4 receptors

    Giuliani D, Neri L, Canalini F, Calevro A, Ottani A, Vandini E et al. · Molecular and cellular neurosciences · 2015PubMed Verified

26. 26.
    Melanocortin 4 receptor activates ERK-cFos pathway to increase brain-derived neurotrophic factor expression in rat astrocytes and hypothalamus

    Ramírez D, Saba J, Carniglia L, Durand D, Lasaga M, Caruso C · Molecular and cellular endocrinology · 2015PubMed Verified

27. 27.
    Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole

    Modi ME, Inoue K, Barrett CE, Kittelberger KA, Smith DG, Landgraf R et al. · Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015PubMed Verified

28. 28.
    Homogeneous fluorescence anisotropy-based assay for characterization of ligand binding dynamics to GPCRs in budded baculoviruses: the case of Cy3B-NDP-α-MSH binding to MC4 receptors

    Veiksina S, Kopanchuk S, Mazina O, Link R, Lille A, Rinken A · Methods in molecular biology (Clifton, N.J.) · 2015PubMed Verified

29. 29.
    Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

    Ottani A, Neri L, Canalini F, Calevro A, Rossi R, Cappelli G et al. · European journal of pharmacology · 2014PubMed Verified

30. 30.
    Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease

    Giuliani D, Galantucci M, Neri L, Canalini F, Calevro A, Bitto A et al. · European journal of pharmacology · 2014PubMed Verified

31. 31.
    Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy in rats

    Lonati C, Carlin A, Leonardi P, Valenza F, Bosari S, Catania A et al. · Peptides · 2013PubMed Verified

32. 32.
    α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice

    Rinne P, Penttinen AM, Nordlund W, Ahotupa M, Savontaus E · PloS one · 2013PubMed Verified

33. 33.
    Gamma-melanocyte stimulating hormone regulates the expression and cellular localization of epithelial sodium channel in inner medullary collecting duct cells

    Cope G, Kaushik G, O'Sullivan SM, Healy V · Peptides · 2013PubMed Verified

34. 34.
    Effects of nesfatin-1 on food intake and LH secretion in prepubertal gilts and genomic association of the porcine NUCB2 gene with growth traits

    Lents CA, Barb CR, Hausman GJ, Nonneman D, Heidorn NL, Cisse RS et al. · Domestic animal endocrinology · 2013PubMed Verified

35. 35.
    Activation of MAPK by inverse agonists in six naturally occurring constitutively active mutant human melanocortin-4 receptors

    Mo XL, Tao YX · Biochimica et biophysica acta · 2013PubMed Verified

36. 36.
    Up-regulation of the canonical Wnt-3A and Sonic hedgehog signaling underlies melanocortin-induced neurogenesis after cerebral ischemia

    Spaccapelo L, Galantucci M, Neri L, Contri M, Pizzala R, D'Amico R et al. · European journal of pharmacology · 2013PubMed Verified

37. 37.
    Three novel human sporadic melanoma cell lines: signaling pathways controlled by MC1R, BRAF and β-catenins

    Zanna P, Maida I, Grieco C, Guida S, Turpin Sevilla MC, De Summa S et al. · Journal of biological regulators and homeostatic agents · 2013PubMed Verified

38. 38.
    Molecular characterization of human melanocortin-5 receptor ligand-receptor interaction

    Yang Y, Mishra VK, Chen M, Duffee E, Dimmitt R, Harmon CM · Biochemistry · 2013PubMed Verified

39. 39.
    NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis

    Figueiredo J, Ferreira AE, Silva RL, Ulloa L, Grieco P, Cunha TM et al. · Naunyn-Schmiedeberg's archives of pharmacology · 2013PubMed Verified

40. 40.
    Functions of the third intracellular loop of the human melanocortin-3 receptor

    Wang ZQ, Tao YX · Current pharmaceutical design · 2013PubMed Verified

41. 41.
    Synthesis and characterization of a melanoma-targeted fluorescence imaging probe by conjugation of a melanocortin 1 receptor (MC1R) specific ligand

    Tafreshi NK, Huang X, Moberg VE, Barkey NM, Sondak VK, Tian H et al. · Bioconjugate chemistry · 2012PubMed Verified

42. 42.
    [Nle3,d-Phe6 ]-γ2 -melanocyte-stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ2 -melanocyte-stimulating hormone in anaesthetized rats

    Cope G, Flanagan ET, Houghton BL, Walsh SA, Johns EJ, Healy V · Clinical and experimental pharmacology & physiology · 2013PubMed Verified

43. 43.
    The melanocortin 4 receptor: oligomer formation, interaction sites and functional significance

    Chapman KL, Findlay JB · Biochimica et biophysica acta · 2013PubMed Verified

44. 44.
    Hemodynamic actions and mechanisms of systemically administered α-MSH analogs in mice

    Rinne P, Tikka S, Mäkelä S, Streng T, Savontaus E · Peptides · 2012PubMed Verified

45. 45.
    Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands

    Beaumont KA, Smit DJ, Liu YY, Chai E, Patel MP, Millhauser GL et al. · Pigment cell & melanoma research · 2012PubMed Verified

46. 46.
    MC1R variant allele effects on UVR-induced phosphorylation of p38, p53, and DDB2 repair protein responses in melanocytic cells in culture

    Wong SS, Ainger SA, Leonard JH, Sturm RA · The Journal of investigative dermatology · 2012PubMed Verified

47. 47.
    Protective action of NDP-MSH in experimental subarachnoid hemorrhage

    Gatti S, Lonati C, Acerbi F, Sordi A, Leonardi P, Carlin A et al. · Experimental neurology · 2012PubMed Verified

48. 48.
    Melanotan-associated transverse melanonychia

    Paurobally D, El Hayderi L, Richert B, Andre J, Nikkels AF · Journal of the European Academy of Dermatology and Venereology : JEADV · 2013Case ReportPubMed Verified

49. 49.
    An eruptive pigmented lesion after melanotan injection

    Ferrándiz-Pulido C, Fernández-Figueras MT, Quer A, Ferrándiz C · Clinical and experimental dermatology · 2011Case ReportPubMed Verified

50. 50.
    Melanocortin 4 receptor activation protects against testicular ischemia-reperfusion injury by triggering the cholinergic antiinflammatory pathway

    Minutoli L, Bitto A, Squadrito F, Irrera N, Rinaldi M, Nicotina PA et al. · Endocrinology · 2011PubMed Verified