Quick summary
Alpha-MSH is an endogenous tridecapeptide driving skin pigmentation via MC1R with potent anti-inflammatory effects. Afamelanotide (Scenesse) is FDA-approved for erythropoietic protoporphyria.
Overview
Alpha-MSH (α-Melanocyte-Stimulating Hormone) is an endogenous tridecapeptide derived from POMC (pro-opiomelanocortin). It is a non-selective agonist at melanocortin receptors MC1R–MC5R, driving skin pigmentation via melanogenesis and exerting potent anti-inflammatory effects through central and peripheral pathways. Synthetic analogs include afamelanotide (melanotan I) and melanotan II.
Mechanism of action
α-MSH binds melanocortin receptors with highest affinity at MC1R (Ki ≈ 0.23 nM), activating Gs-protein signaling and increasing intracellular cAMP. At melanocytes, cAMP activates MITF transcription factor, upregulating tyrosinase and inducing melanin synthesis. At immune cells, α-MSH suppresses NF-κB activation, reducing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and promoting anti-inflammatory pathways. MC4R signaling in the hypothalamus mediates appetite suppression and energy homeostasis effects.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| anti-inflammatory research (animal) | subcutaneous | 50–500 mcg/kg | once or twice daily per protocol | |
| melanogenesis studies (in vitro) | intravenous | 1–10 nM | per experiment |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Extensive preclinical and clinical research demonstrates α-MSH's dual role in pigmentation and immunomodulation. Studies show significant anti-inflammatory effects in models of colitis, arthritis, and uveitis. The synthetic linear analog afamelanotide is FDA-approved for erythropoietic protoporphyria. Research also explores α-MSH in neuroprotection, ischemia-reperfusion injury, and fever regulation. Melanotan II (cyclic analog) has been widely studied for tanning and sexual function but is not approved for human use.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Alpha-MSH for synergistic effects.
Legal status
Endogenous α-MSH is available for laboratory research only. Synthetic analogs (melanotan I/II) are not approved for human use in the US. Afamelanotide (Scenesse) is FDA-approved for erythropoietic protoporphyria as a prescription drug.
Sourcing & access
Research compound
Alpha-MSH is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Alpha-MSH (alpha-Melanocyte-Stimulating Hormone) is an endogenous tridecapeptide derived from POMC (pro-opiomelanocortin). It is a non-selective agonist at melanocortin receptors MC1R through MC5R, driving skin pigmentation and exerting potent anti-inflammatory effects through central and peripheral pathways.
Alpha-MSH binds MC1R with high affinity, activating Gs-protein signaling and increasing cAMP. At melanocytes, this activates MITF transcription factor and upregulates tyrosinase to induce melanin synthesis. At immune cells, it suppresses NF-kB activation and reduces pro-inflammatory cytokines. MC4R signaling mediates appetite suppression.
Alpha-MSH is a research compound with reported side effects including nausea, flushing, spontaneous erections (MC4R mediation), and hyperpigmentation with repeated dosing. The FDA-approved analog afamelanotide has a well-established clinical safety profile for its approved indication.
Melanotan II is a cyclic synthetic analog of alpha-MSH with broader receptor activity and greater metabolic stability. While alpha-MSH is the endogenous linear peptide with a short half-life of 10-20 minutes, melanotan II is a modified version studied for tanning and sexual function but not approved for human use.
Research references
- Melanocortin-4 receptor complexity in energy homeostasis, obesity and drug development strategiesReview
- Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous SystemPubMed
- Structures of active melanocortin-4 receptor-Gs-protein complexes with NDP-alpha-MSH and setmelanotidePubMed
- The central melanocortin system as a treatment target for obesity and diabetes: A brief overviewReview
- Melanocortin receptor agonists suppress experimental autoimmune uveitisPubMed