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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 3
pubmed May 1, 1992

MSH receptor expression and the relationship to melanogenesis and metastatic activity in B16 melanoma.

Lunec. J J; Pieron. C C; Thody. A J AJ

The study looked at how different hormone-like peptides, including melanotan‑I (a synthetic version of alpha‑MSH), affect skin pigment production and the spread of melanoma cells in the lab. All the peptides boosted pigment, but they also increased the cells' ability to spread, with melanotan‑I being the most potent. The researchers found that the strength of the effect isn’t just about how tightly the peptide binds to its receptor.

Utility 3
pubmed Aug 28, 1981

Calcium-dependent prolonged effects on melanophores of [4-norleucine, 7-D-phenylalanine]-alpha-melanotropin.

Hadley. M E ME; Anderson. B B; Heward. C B CB; Sawyer. T K TK; Hruby. V J VJ

In frogs, a one‑time shot of the melanotan‑I analog kept the skin dark for at least six weeks, far longer than the natural hormone. The darkening stayed as long as calcium was present; removing calcium lightened the skin, and adding it back re‑darkened it without any more peptide.

Utility 3
pubmed 1996

Three-dimensional molecular models of the hMC1R melanocortin receptor: complexes with melanotropin peptide agonists.

Haskell-Luevano. C C; Sawyer. T K TK; Trumpp-Kallmeyer. S S; Bikker. J A JA; Humblet. C C; Gantz. I...

Scientists built a 3‑D computer model of the human MC1R receptor (the skin‑pigment receptor) and fitted three melanotropin peptides—including melanotan‑II—into the predicted binding site. They mapped which parts of the peptides stick to which parts of the receptor, explaining why some versions are stronger and last longer.

Utility 2
pubmed Jan 10, 2023

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. Eleonora E; Vandini. Eleonora E; Bodria. Martina M; Liao. Wenjie W; Baraldi. Carlo C; Secco....

In mouse studies, a drug similar to the skin‑tanning peptide melanotan‑I helped older Alzheimer’s‑model mice think better and reduced some brain inflammation markers, but it didn’t lower the amyloid plaques that are typical of the disease. The benefits were seen only at certain ages and didn’t affect all brain pathways.

Utility 2
pubmed Apr 28, 2024

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. Guadalupe G; Scimonelli. Teresa T; Lasaga. Mercedes M; Granero. Gladys G; Onnainty. Ren&#xe...

Scientists made tiny particles that can carry a melanin‑stimulating hormone fragment (NDP‑MSH) into the brain of rats, and this helped reverse memory problems caused by a high‑fat diet and inflammation. The particles can cross the blood‑brain barrier and reach hippocampal neurons, but the work is still in early animal testing.

Utility 2
pubmed May 21, 2015

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

Giuliani. Daniela D; Neri. Laura L; Canalini. Fabrizio F; Calevro. Anita A; Ottani. Alessandra A; Va...

A study in Alzheimer‑model mice found that daily low‑dose injections of the peptide NDP‑α‑MSH (melanotan‑I) improved memory and boosted the creation of new brain cells, without obvious side effects. The benefits disappeared when a drug that blocks the MC4 receptor was given, showing the effect depends on that receptor.

Utility 2
pubmed Jul 1, 2024

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

Carniglia. Lila L; Turati. Juan J; Saba. Julieta J; López Couselo. Federico F; Romero. Ana Clar...

A lab study found that activating the MC4R receptor with a melanocortin analog (NDP‑MSH) makes rat brain stem cells in the hippocampus multiply more and stay in a youthful state, and this effect depends on the PPAR‑γ pathway. The work was done in isolated cells, not in living animals or people, and used a specific lab‑grade compound, not the consumer peptide melanotan‑I.

Utility 2
pubmed Jun 9, 2010

Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?

Langan. E A EA; Nie. Z Z; Rhodes. L E LE

People are buying and injecting unregulated melanotan I or II to get a tan without sun, but this can expose them to dirty needles, unknown impurities, and can hide skin problems, making diagnosis harder. A safer, regulated version called afamelanotide is being tested for protecting skin from UV damage, but it’s not yet widely available.

Utility 2
pubmed Nov 17, 2010

Signaling from the human melanocortin 1 receptor to ERK1 and ERK2 mitogen-activated protein kinases involves transactivation of cKIT.

Herraiz. Cecilia C; Journé. Fabrice F; Abdel-Malek. Zalfa Z; Ghanem. Ghanem G; Jiménez-Cer...

The study shows that the skin‑color receptor MC1R, which melanotan‑I (a synthetic α‑MSH peptide) activates, can turn on a cell‑growth pathway (ERK) by hijacking another receptor called cKIT, and it does this without using the usual cAMP route. This happens even in people with red‑hair MC1R variants, and it doesn’t involve protein kinase C.

Utility 2
pubmed Nov 12, 2020

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. Siming S; Luo. Xu X; Wu. Xuan X; Zhang. Tongyu T; Gu. Linggui L; Wang. Yiying Y; Gao. Meng M; Ch...

A mouse study found that a synthetic peptide called NDP‑MSH, which activates the melanocortin‑1 receptor, can lessen brain swelling, oxidative damage, and cell death after a brain bleed by turning on a protective PI3K/Akt/Nrf2 pathway. The effect disappears if the receptor or the pathway is blocked.

Utility 2
pubmed Nov 19, 2008

Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke.

Ottani. Alessandra A; Giuliani. Daniela D; Mioni. Chiara C; Galantucci. Maria M; Minutoli. Letteria...

In rats, a stroke triggers harmful inflammation and cell death not only in the brain but also in the liver. Giving a synthetic melanin‑stimulating hormone (similar to melanotan‑I) a few hours after the stroke cuts down this inflammation and protects cells, but only if the vagus nerve’s cholinergic (acetylcholine) pathway is intact. Cutting the vagus nerve or blocking its receptors removes the benefit, showing the nerve is key to the protection.

Utility 2
pubmed Jun 19, 2010

Interactions of the melanocortin-4 receptor with the peptide agonist NDP-MSH.

Chapman. Kathryn L KL; Kinsella. Gemma K GK; Cox. Alan A; Donnelly. Dan D; Findlay. John B C JB

Scientists mapped exactly which parts of the MC4R receptor touch the melanotan‑I peptide, pinpointing several key amino acids that interact with the peptide’s core and ends. This deepens our understanding of how the peptide activates the receptor but doesn’t change how you would currently use it.

Utility 2
pubmed Nov 1, 2007

Effects of ghrelin, corticotrophin-releasing hormone, and melanotan-II on food intake in rats with paraventricular nucleus lesions.

Wang. J J; Ling. S S; Usami. T T; Murata. T T; Narita. K K; Higuchi. T T

In rats, destroying a brain area called the PVN makes them eat more and become obese. Giving them ghrelin (a hunger hormone) makes them eat even more, while giving CRH (a stress hormone) cuts their eating, especially in the PVN‑damaged rats. Melanotan‑II, a synthetic peptide often used for skin tanning, normally reduces food intake, but it stops working in rats with PVN damage, suggesting its appetite‑suppressing effect depends on that brain region.

Utility 2
pubmed Jul 22, 2011

Melanocortin 4 receptor activation induces brain-derived neurotrophic factor expression in rat astrocytes through cyclic AMP-protein kinase A pathway.

Caruso. Carla C; Carniglia. Lila L; Durand. Daniela D; Gonzalez. Patricia V PV; Scimonelli. Teresa N...

The study shows that activating the MC4R receptor with melanotan‑I‑like compounds in rat brain cells raises levels of BDNF, a protein linked to brain health, through a cAMP‑PKA‑CREB signaling chain. This effect was blocked when the receptor or the signaling steps were inhibited, confirming the pathway. However, the work was done only in cultured rat astrocytes, not in living animals or humans, so practical take‑aways are limited.

Utility 2
pubmed Aug 9, 2011

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

Minutoli. Letteria L; Bitto. Alessandra A; Squadrito. Francesco F; Irrera. Natasha N; Rinaldi. Maria...

In rats, a drug that mimics the natural hormone α‑MSH (called NDP‑α‑MSH or melanotan‑I) activated the MC4 receptor and, through the vagus nerve, lowered inflammation and tissue damage after the testicles were briefly cut off from blood. The benefit disappeared if the nerve was cut or if the MC4 receptor was blocked. Over a month, the drug also helped sperm production and reduced cell death.

Utility 2
pubmed Dec 1, 2006

Point mutations in the melanocortin-4 receptor cause variable obesity in mice.

Meehan. Thomas P TP; Tabeta. Koichi K; Du. Xin X; Woodward. Lanette S LS; Firozi. Karen K; Beutler....

Scientists found that two different mutations in the mouse MC4R gene, which is linked to obesity, change how the receptor works. One mutation makes the receptor harder to reach on the cell surface, while the other lets it get to the surface but stops it from signaling properly. Mice with the weaker‑signaling mutation got fatter, showing that how much the receptor still works predicts obesity severity.

Utility 2
pubmed Jan 22, 2007

Selective melanocortin MC4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage.

Giuliani. D D; Mioni. C C; Bazzani. C C; Zaffe. D D; Botticelli. A R AR; Capolongo. S S; Sabba. A A;...

In rats that lost a lot of blood, drugs that specifically activate the MC4 receptor helped bring heart and breathing back to normal, cut harmful free radicals, and kept organs from damage, leading to better survival. The benefits disappeared when another drug blocked the MC4 receptor, showing the effect is truly due to MC4 activation.

Utility 2
pubmed Jun 8, 2010

Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist.

Xiang. Zhimin Z; Proneth. Bettina B; Dirain. Marvin L ML; Litherland. Sally A SA; Haskell-Luevano. C...

The paper tested how 30 different human MC4R gene variants react to natural hormones and synthetic peptides like NDP‑MSH and MTII (similar to melanotan‑I). Some variants still work fully but need higher amounts, others only give a weak response, and a few change how the natural blocker (AGRP) works. For DIY biohackers, this means your MC4R genetics could affect how well melanotan‑I influences appetite, weight, or other MC4R‑related effects, but the study was done in cells, not people.

Utility 2
pubmed Oct 22, 2014

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

Ottani. Alessandra A; Neri. Laura L; Canalini. Fabrizio F; Calevro. Anita A; Rossi. Rosario R; Cappe...

In a rat study, giving the peptide NDP‑α‑MSH (a melanocortin similar to melanotan‑I) during CPR after a heart‑stop event helped the animals recover better: blood pressure and heart rate returned toward normal, the blood’s acidity improved, and fewer harmful inflammation signals were seen. Overall survival jumped from about half to over 80%.