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Melanotan-I

Afamelanotide, MT-I, [Nle4-D-Phe7]-α-MSH, Scenesse, CUV-1647

A synthetic analog of alpha-melanocyte-stimulating hormone that stimulates melanogenesis, increasing skin pigmentation and providing photoprotection against UV radiation.

Quick Stats
Studies 225
Trials 100
Formula C78H111N21O19
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Utility 1
pubmed Nov 25, 1997

Alpha-melanocyte-stimulating hormone and endothelin-1 have opposing effects on melanocyte adhesion, migration, and pp125FAK phosphorylation.

Scott. G G; Cassidy. L L; Abdel-Malek. Z Z

The study shows that the alpha‑MSH analog (melanotan‑I) changes skin cell (melanocyte) shape and makes them stick more tightly to the surrounding matrix, while a different molecule, endothelin‑1, does the opposite by boosting cell movement and reducing stickiness. These effects are linked to different internal signaling pathways, but the research doesn’t provide any direct health‑boosting protocol for longevity or performance.

Utility 1
pubmed 1996

Enhanced binding and inertness to dehalogenation of alpha-melanotropic peptides labeled using N-succinimidyl 3-iodobenzoate.

Garg. P K PK; Alston. K L KL; Welsh. P C PC; Zalutsky. M R MR

Scientists tested two ways to stick a radioactive tag onto a skin‑pigment peptide used for targeting melanoma cells. The newer tagging method (using SIB) stuck better to the cells and broke down less, meaning less stray radioactivity in the body, but this is mainly a research tool, not a new way to use melanotan‑I for personal health.

Utility 1
pubmed Mar 1, 2010

Laurdan spectrum decomposition as a tool for the analysis of surface bilayer structure and polarity: a study with DMPG, peptides and cholesterol.

Lúcio. Aline D AD; Vequi-Suplicy. Cíntia C CC; Fernandez. Roberto M RM; Lamy. M Teresa MT

The study shows a better way to look at how molecules sit on cell membranes using a fluorescent dye called Laurdan. By splitting the dye’s light signal into two parts, researchers can see tiny changes in membrane packing and water content more clearly than with older methods. They used this technique to compare a natural hormone (alpha‑MSH) and a stronger lab‑made version, finding that the stronger version makes the membrane surface stiffer, while the natural hormone mainly dries out the membrane surface.

Utility 1
pubmed 1995

Identification of a melanocortin receptor expressed by murine brain microvascular endothelial cells in culture.

de Angelis. E E; Sahm. U G UG; Ahmed. A R AR; Olivier. G W GW; Notarianni. L J LJ; Branch. S K SK; M...

Scientists discovered that mouse brain blood‑vessel cells have a receptor that binds the hormone alpha‑MSH, which melanotan‑I mimics. They showed the receptor is present but don’t know what it does, so there’s no clear way to use this info yet.

Utility 1
pubmed 1995

Opioid peptide inhibition of endogenous norepinephrine release from the A2 noradrenergic cell group in vitro.

Carr. J A JA; Gregg. K J KJ

The study shows that a melanotropin peptide similar to melanotan‑I does not change norepinephrine release in a specific brain area, while opioid peptides do reduce it via mu‑opioid receptors. This means melanotan‑I probably won’t affect stress‑ or metabolism‑related norepinephrine pathways in the way some users might hope.

Utility 1
pubmed 1994

Cloning and expression of a new member of the melanocyte-stimulating hormone receptor family.

Barrett. P P; MacDonald. A A; Helliwell. R R; Davidson. G G; Morgan. P P

Scientists found a new melanocortin receptor in sheep that can bind alpha‑MSH‑like peptides, including a strong synthetic version called NDP‑MSH, and it triggers the usual cell signaling. The work is purely a lab discovery and doesn’t give any new instructions for using melanotan‑i or related peptides.

Utility 1
pubmed Apr 1, 1988

Improved recovery of nigro-striatally hemitransected rats induced by (Nle4, D-Phe7)alpha-MSH: a central effect.

Zanoli. P P; Benelli. A A; Bertolini. A A

In a rat study, a synthetic version of the hormone alpha‑MSH (called (Nle4, D-Phe7)alpha‑MSH) was pumped directly into the brain after a type of brain injury that mimics Parkinson's disease. The treated rats showed better movement, less abnormal turning, and changes in dopamine receptors compared to rats that got just saline. However, the treatment was given by direct brain infusion, which isn’t practical for people, and the work was done in animals, not humans.

Utility 1
pubmed Oct 1, 2000

Development of a facile method for high throughput screening with reporter gene assays.

Goetz. A S AS; Andrews. J L JL; Littleton. T R TR; Ignar. D M DM

The paper describes a new lab method for quickly testing many compounds using cells that light up when a specific receptor is activated. Melanotan‑I was used as a test molecule to show the system works, but the study does not give any dosing, safety, or health‑benefit information for people.

Utility 1
pubmed 2004

Agouti-related protein (83-132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands.

Pritchard. L E LE; Armstrong. D D; Davies. N N; Oliver. R L RL; Schmitz. C A CA; Brennand. J C JC; W...

The study shows that a fragment of the protein agouti‑related protein (AGRP 83‑132) blocks the human melanocortin‑4 receptor (MC4‑R) in a straightforward, competitive way, without any fancy allosteric tricks. It also finds that many natural hormones derived from POMC, like different forms of melanocyte‑stimulating hormone, bind the same receptor with similar strength, meaning they could all play a role in controlling appetite.

Utility 1
pubmed Feb 9, 2001

Enhancement of gene delivery by an analogue of alpha-MSH in a receptor-independent fashion.

Chluba. J J; Lima de Souza. D D; Frisch. B B; Schuber. F F

Scientists found that a short piece of the hormone alpha‑MSH can boost the delivery of DNA into cells, even when the cells don't have the usual hormone receptor. The peptide seems to act like a membrane‑disrupting helper, making gene‑transfer methods more efficient, but the work is purely lab‑based and not a health‑oriented protocol.

Utility 1
pubmed Dec 1, 1998

Amino acid residues in third intracellular loop of melanocortin 1 receptor are involved in G-protein coupling.

Frändberg. P A PA; Doufexis. M M; Kapas. S S; Chhajlani. V V

The study shows that specific parts of the MC1R receptor (the third intracellular loop) are needed for the receptor to talk to inside‑the‑cell proteins (G‑proteins). Changing these amino acids stops the normal signal (cAMP) even though the peptide still binds, meaning the receptor can't work properly without them.

Utility 1
pubmed Mar 17, 2005

The regulation of feeding and metabolic rate and the prevention of murine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist.

Markison. Stacy S; Foster. Alan C AC; Chen. Chen C; Brookhart. Gregor B GB; Hesse. Amy A; Hoare. Sam...

Scientists gave mice a drug that blocks the MC4‑R receptor from the outside of the body. The drug made the mice eat more and burn fewer calories, and it helped keep muscle mass in mice with cancer‑related wasting. However, this work is done in rodents, uses a small‑molecule antagonist, and does not involve melanotan‑I, which is an MC1‑R agonist used by some biohackers.

Utility 1
pubmed Jun 18, 2013

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

Mo. Xiu-Lei XL; Tao. Ya-Xiong YX

The study found that some chemicals that block the usual MC4R signaling (the Gs‑cAMP pathway) can actually turn on a different pathway (ERK1/2 MAPK) in both normal and mutant MC4 receptors. This effect varies depending on the specific receptor mutation and the chemical used, but the research does not test melanotan‑I or give any dosing guidance.

Utility 1
pubmed Oct 20, 1997

The roles of valine 208 and histidine 211 in ligand binding and receptor function of the ovine Mel1a beta melatonin receptor.

Conway. S S; Canning. S J SJ; Barrett. P P; Guardiola-Lemaitre. B B; Delagrange. P P; Morgan. P J PJ

Scientists changed two building blocks (valine 208 and histidine 211) in a sheep melatonin receptor to see how they affect melatonin binding and signaling. All the altered receptors still showed up in cells, but they bound melatonin less tightly, and the ones with the histidine change stopped responding to melatonin altogether.

Utility 1
pubmed 2004

The role of melanocortin-3 and -4 receptor in regulating appetite, energy homeostasis and neuroendocrine function in the pig.

Barb. C R CR; Robertson. A S AS; Barrett. J B JB; Kraeling. R R RR; Houseknecht. K L KL

In pigs, activating brain receptors MC3/4 with a drug called NDP‑MSH reduced how much they ate, but blocking those receptors didn’t make them eat more. The study also found that a common MC4‑R mutation in pigs might change how these receptors work, and the drugs didn’t affect growth‑hormone or luteinising‑hormone levels.

Utility 1
pubmed 1996

Human epidermal melanocyte and keratinocyte melanocortin receptors: visualization by melanotropic peptide conjugated microspheres (latex beads).

Jiang. J J; Sharma. S D SD; Hruby. V J VJ; Bentley. D L DL; Fink. J L JL; Hadley. M E ME

The study shows that a synthetic version of the hormone alpha‑MSH (called [Nle4,D-Phe7]alpha‑MSH) can be attached to tiny latex beads, and these beads stick specifically to skin cells that have melanocortin receptors – mainly melanocytes (the cells that make pigment) and also keratinocytes. The binding can be blocked by the free hormone, proving the interaction is specific.

Utility 1
pubmed 1987

Regulation of cell shape in the Cloudman melanoma cell line.

Preston. S F SF; Volpi. M M; Pearson. C M CM; Berlin. R D RD

In a lab study, a synthetic version of the hormone alpha‑MSH (similar to melanotan‑I) made melanoma cells grow thin, branch‑like extensions. This shape change was linked to two internal signals: raising cAMP levels and blocking a protein called PKC. Turning PKC on made the cells round up again, and the cells only went back to their original shape when they could make new proteins and RNA.

pubmed Jul 7, 2006

Nuclear gene indicates coat-color polymorphism in mammoths.

Römpler. Holger H; Rohland. Nadin N; Lalueza-Fox. Carles C; Willerslev. Eske E; Kuznetsova. Tat...

Scientists decoded a gene that controls pigment in woolly mammoths and found two versions—one that works well and one that works poorly—meaning ancient mammoths likely had both dark and light fur. This discovery is about ancient animal genetics, not about using the peptide melanotan‑i for health or performance.

pubmed Nov 27, 2012

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

Tafreshi. Narges K NK; Huang. Xuan X; Moberg. Valerie E VE; Barkey. Natalie M NM; Sondak. Vernon K V...

Scientists made a glowing molecule that sticks to a protein often found on melanoma skin cancers, letting surgeons see tumors more clearly during operations. This is a research tool, not a supplement or treatment you can use yourself.