α-MSH

α-melanotropin, alpha-MSH, melanotropin, POMC(138–150); sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2

Sexual health, hormones & signalling

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Summary

Class: Naturally occurring 13-amino-acid peptide hormone cut from the larger pro-opiomelanocortin (POMC) protein; the parent molecule of afamelanotide, Melanotan II, bremelanotide, setmelanotide and the KPV fragment
Mechanism: Activates melanocortin receptors MC1R (skin pigmentation, anti-inflammatory), MC3R and MC4R (appetite, energy balance, sexual function) and MC5R (sebaceous and exocrine glands)
Routes studied: Intravenous and subcutaneous (older human studies); intracerebroventricular, intranasal, IV and topical (animal); topical (cosmetic); community: subcutaneous and intranasal, rarely
Dose range reported: Human pigmentation studies (1960s): roughly 1–10 mg/day by injection for several days. Animal anti-inflammatory work: µg to low-mg/kg systemically, ng–µg centrally. No validated human dose for any indication. Community reports are sparse and unquantified
Half-life: Minutes in plasma (rapid breakdown by peptidases), which is why every therapeutic analogue was modified for stability
Storage: Lyophilised: refrigerate or freeze, protect from light; the methionine at position 4 oxidises readily. Reconstituted: refrigerate, short shelf life
Regulatory status: Not approved as a medicine anywhere; endogenous hormone. Three of its analogues are approved medicines

Doses are as reported in studies or by the community — never recommendations.

1What it is

α-MSH is a hormone the body makes by cutting up POMC, the same precursor that yields ACTH and β-endorphin. In humans it is produced mainly in the skin (by keratinocytes and melanocytes in response to UV light), in the hypothalamus (by POMC neurons that regulate appetite) and in immune cells; the pituitary intermediate lobe that is the main source in rodents is vestigial in adult humans. It was isolated in the 1950s by Aaron Lerner, who in 1961 showed that injecting it into people darkened their skin.

Because it breaks down within minutes, α-MSH itself has never been a practical drug. Its importance is as the template: Melanotan I (afamelanotide), Melanotan II, bremelanotide (PT-141), setmelanotide and the anti-inflammatory tripeptide KPV (its last three amino acids) are all derived from it. It is naturally occurring, not a synthetic research compound, though synthetic copies are what circulate in research and community settings.

2How it's thought to work

MC1R (melanocytes, immune cells, endothelium). raises cAMP, which switches melanin production to the dark eumelanin form and enhances DNA repair after UV damage. On immune cells it suppresses NF-κB signalling, reducing TNF-α, IL-1, IL-6 and adhesion-molecule expression, and induces IL-10. This is the basis of the extensive anti-inflammatory literature.

MC4R and MC3R (hypothalamus, brainstem, spinal cord). reduce food intake, raise energy expenditure and modulate sexual arousal and erectile function. People with POMC mutations who cannot make α-MSH develop severe early obesity, red hair and adrenal insufficiency (Krude 1998, Nat Genet), the clearest human evidence for its role.

MC5R. sebum and pheromone-gland secretion in animals; function in humans less clear.

Context dependence. the same molecule tans skin, dampens inflammation and suppresses appetite depending on which receptor and tissue it reaches, which is why selective analogues were developed.

Alpha-MSH, cut from the POMC precursor, acting across the melanocortin receptors. At MC1R on the melanocyte it drives melanin and darkens skin; at MC4R in the brain it reduces food intake — one natural ligand, and the receptor it meets decides the effect.Schematic — not to scale

3What the research shows

Skin pigmentation

Daily injections of purified α-MSH darkened the skin of human volunteers within days, reversing after stopping (Lerner & McGuire 1961, Nature). The effect was reproduced with the stable analogue Melanotan I in the 1990s and underlies afamelanotide's approval. Original studies were small and uncontrolled. [1]

Graded C/D (α-MSH itself); A for analogues in specific conditions

Anti-inflammatory and immunomodulatory effects

Hundreds of cell and animal studies show α-MSH reduces inflammation in models of septic shock, arthritis, colitis, uveitis, ischaemia-reperfusion injury, brain inflammation and skin inflammation (reviews: Lipton & Catania 1997, Immunol Today; Catania 2004, Pharmacol Rev; Brzoska 2008, Endocr Rev). In humans, plasma α-MSH is altered in sepsis and inflammatory disease, but no controlled trial of α-MSH itself exists. A stable α-MSH analogue (ABT-719/AP214) failed to prevent acute kidney injury after cardiac surgery in a phase 2b trial (McCullough 2016, J Am Heart Assoc). [2][3][4][8]

Graded C; human genetic evidence strong

Appetite and energy balance

Central MC4R agonism suppresses feeding in rodents (Fan 1997, Nature), and MC4R knockout mice are obese (Huszar 1997, Cell). Human POMC deficiency confirms the pathway's relevance (Krude 1998). Setmelanotide (this batch) is the clinical translation; α-MSH itself has not been tested for weight in humans. [5][6][7]

Graded C/B (analogues)

Sexual function

Melanocortin induce erections in rodents and, in the form of Melanotan II and bremelanotide, in humans. No human data for α-MSH itself.

Fever and neuroprotection

α-MSH is an endogenous antipyretic in rabbits and rodents and reduces injury in stroke and brain-trauma models. Not studied in humans.

Community use

Because the molecule is unstable, community interest usually migrates to Melanotan II, afamelanotide or KPV. The few reports of injected or intranasal α-MSH describe mild flushing and nausea and no clear effect; anecdotal only.

4Reported side effects and interactions

Literature-reported

Literature (human, historical infusions). skin darkening, occasional flushing and nausea. Data are from a handful of small studies decades ago; no systematic safety evaluation exists.

Community-reported

Community-reported (α-MSH itself). sparse; flushing, nausea, headache, injection-site soreness.

Analogue class data (relevant by mechanism). nausea, flushing, yawning, reduced appetite, spontaneous erections, darkening of moles and new naevi, with case reports of melanoma in Melanotan II users (causality unproven); hyperpigmentation with setmelanotide and afamelanotide; blood-pressure rises with some older MC4R .

Theoretical. stimulation of existing melanocytic lesions; interaction with the HPA axis is unlikely at MC1R/MC4R-selective doses but α-MSH shares its first 13 amino acids with ACTH, and very high doses could in principle have weak ACTH-like effects; immune suppression at high sustained exposure is plausible from the mechanism.

Interactions. additive with other melanocortin agonists (Melanotan II, bremelanotide, setmelanotide, afamelanotide); UV exposure amplifies pigmentation; no pharmacokinetic interactions are known.

Markers researchers commonly monitor

No compound-specific human markers are established. Based on melanocortin physiology and analogue experience:

Marker	Why it's watched
Skin and mole examination with photographs	pigmentation is the one reliably demonstrated human effect, and darkening or changing naevi need a dermatologist, not a self-assessment.
Blood pressure and heart rate	MC4R agonism has raised blood pressure with some analogues; a home cuff is sufficient.
hs-CRP and a symptom diary	if the rationale is anti-inflammatory, this is the only accessible systemic marker, with the caveat that no human effect has been shown.
Appetite and weight log	MC4R effects on hunger are the most likely subjective change.
Morning cortisol	only if high or repeated doses are involved, given the shared sequence with ACTH; not expected to change at ordinary exposures.
CBC and CMP	general baseline for any injected compound with no modern human safety data.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied, when available for research, as powder in small vials. The molecule is fragile: oxidation of methionine-4 and rapid enzymatic degradation mean solutions should be made fresh, kept cold and protected from light. with , swirl gently. Because the is minutes, any biological effect from a bolus is brief.

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6Commonly studied alongside

KPV (its C-terminal tripeptide, studied for gut inflammation), Melanotan II and afamelanotide/Melanotan I (stable pigmentation analogues), bremelanotide/PT-141 (sexual function), setmelanotide (this batch; obesity), ACTH/tetracosactide (shares the N-terminal sequence), oxytocin and vasopressin (co-studied in hypothalamic signalling research).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; endogenous hormone with no drug product. FDA's 2023 Category 2 compounding list names melanotan II and KPV; whether α-MSH itself is covered †
European Union	Not authorised; its analogue afamelanotide (Scenesse) is authorised for erythropoietic protoporphyria
United Kingdom	Not licensed; afamelanotide licensed
Australia	Not approved; afamelanotide approved †
South Africa	Not registered †
Sport	Not specifically listed by WADA; melanotans likewise not named, but non-approved substances fall under S0 †

8Open questions

Can α-MSH's anti-inflammatory effects be harnessed in humans without the pigmentation and appetite effects? Selective MC1R are in development.
Does intranasal α-MSH reach brain melanocortin receptors in humans?
Is there any safe, validated use for the native molecule, given that every clinical success has come from stabilised analogues?

9References

1Lerner AB, McGuire JS (1961). Effect of alpha- and beta-melanocyte stimulating hormones on the skin colour of man. Nature. DOI
2Lipton JM, Catania A (1997). Anti-inflammatory actions of the neuroimmunomodulator α-MSH. Immunol Today. PubMed · DOI
3Catania A, Gatti S, Colombo G, Lipton JM (2004). Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. PubMed · DOI
4Brzoska T et al. (2008). α-Melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev. PubMed · DOI
5Krude H et al. (1998). Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. PubMed · DOI
6Fan W et al. (1997). Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. PubMed · DOI
7Huszar D et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. PubMed · DOI
8McCullough PA et al. (2016). ABT-719 for the prevention of acute kidney injury in patients undergoing high-risk cardiac surgery: a randomized phase 2b clinical trial. J Am Heart Assoc. PubMed · DOI
9Cone RD (2005). Anatomy and regulation of the central melanocortin system. Nat Neurosci. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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11Page history

26 Oct 2026Profile published — awaiting medical review

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