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Melanocortin System

AMT (Alpha-MSH)

The body's natural tanning and anti-inflammatory melanocortin hormone; parent of afamelanotide, Melanotan II and PT-141.

InvestigationalEvidence level 2 of 5: Animal data, minimal humanAlso: α-Melanocyte-Stimulating Hormone, α-MSH, Alpha-melanotropin

Overview

Alpha-melanocyte-stimulating hormone (α-MSH) is a 13-amino-acid peptide cut from the pro-opiomelanocortin (POMC) precursor in the pituitary, skin and brain. It activates melanocortin receptors: MC1R on pigment cells drives production of dark eumelanin and DNA-repair responses after UV exposure, MC3R and MC4R in the brain influence appetite, energy balance and sexual function, and MC5R affects oil glands. It is also a natural anti-inflammatory signal. Native α-MSH breaks down within minutes, so drug development moved to stabilized analogs such as afamelanotide, Melanotan II and bremelanotide. Pigment stimulation can darken moles and freckles, so baseline and ongoing skin checks are essential, and it should not be used by anyone with a history of melanoma.

Classification
Endogenous 13-amino-acid melanocortin peptide
Route
Subcutaneous
Half-life
Minutes (native α-MSH)

Mechanism of action

Primary targetMelanocortin receptors MC1R, MC3R, MC4R, MC5R
  1. Subcutaneous injectionNative peptide is short-lived; acts quickly on nearby receptors.
  2. MC1R activation in melanocytesRaises cAMP, switching pigment production toward dark eumelanin.
  3. Tyrosinase upregulationIncreased melanin synthesis and transfer to skin cells darkens skin.
  4. Central MC3R/MC4R signalingHypothalamic effects reduce appetite and can increase sexual arousal.
  5. Anti-inflammatory signalingInhibits NF-κB and inflammatory cytokines in immune cells.
Downstream effects
  • Skin pigmentation
  • UV photoprotection
  • Appetite reduction
  • Anti-inflammatory effects

Researched for

  • Photoprotection and tanning
  • Erythropoietic protoporphyria (via afamelanotide)
  • Vitiligo (analogs)
  • Inflammatory conditions
  • Appetite regulation

Research notes

  • Afamelanotide, a stabilized α-MSH analog, increased pain-free sunlight time in EPP RCTs (Langendonk 2015), leading to FDA approval.
  • Native α-MSH degrades within minutes, limiting its practical therapeutic use.
  • Preclinical work shows anti-inflammatory and tissue-protective effects in models of arthritis, colitis and ischemia.
  • MC1R stimulation darkens nevi; long-term melanoma risk is not established.

Reported side effects

  • Facial flushing
  • Nausea
  • Darkening of moles and freckles
  • Spontaneous erections
  • Possible changes in pigmented lesions

Contraindications & cautions

  • Personal or family history of melanoma
  • Atypical/dysplastic nevus syndrome
  • Active skin cancer
  • Pregnancy and breastfeeding
  • Uncontrolled hypertension

Lab monitoring

  • CBC, CMP
  • Vitamin D (25-OH)
  • Blood pressure
  • Baseline dermatology full-skin exam with mole photography
  • Dermatology follow-up every 3–6 months

Dosing and pricing for AMT (Alpha-MSH)

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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