Melanocortin receptor agonist · research peptide

Melanotan II (MT-II)

Studied for: UV-independent skin pigmentation, melanocortin pharmacology research. Documented safety signals: atypical nevi, rhabdomyolysis case reports.

Melanotan II is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH) originally developed at the University of Arizona in the 1980s. It is a broad-spectrum melanocortin receptor agonist — activating MC1R, MC3R, MC4R, and MC5R with no significant MC2R binding — and has been studied primarily for UV-independent tanning. It is not FDA-approved, carries documented safety signals in the dermatology literature, and was included in the April 15, 2026 FDA 503A Category 2 removal.

Class
Broad-spectrum melanocortin receptor agonist
Structure
Synthetic cyclic heptapeptide analog of α-MSH
Receptor profile
MC1R · MC3R · MC4R · MC5R (no significant MC2R)[1][2]
Plasma half-life (SC)
~33 minutes[1]
Effect duration
Hours to days (downstream signaling)[1]
FDA status
Not approved · April 15 2026 503A Cat. 2 removal[3]
Safety signals
Atypical nevi · rhabdomyolysis · priapism (case reports)
Related approved drug
Bremelanotide (Vyleesi) — distinct MC4R-selective molecule
Educational reference only — safety signals exist. Case reports and dermatology literature document new atypical melanocytic nevi, rapid darkening of pre-existing nevi, and cases of rhabdomyolysis in Melanotan II users. This page summarizes the published record. It does not recommend a dose, route, or acquisition channel. Dermatologic evaluation of any pigmented lesion changes is the published-literature precaution in this space.

Last reviewed April 24, 2026 by the Enhanced Health Editorial Team. See the editorial policy.

What Melanotan II is

Melanotan II is a synthetic cyclic heptapeptide — a seven-amino-acid loop — engineered as a stable analog of α-melanocyte-stimulating hormone (α-MSH). It was developed in the 1980s at the University of Arizona. The molecule is distinct from Melanotan I (afamelanotide, approved in Europe for erythropoietic protoporphyria) and from bremelanotide (Vyleesi, FDA-approved for HSDD in premenopausal women), despite shared lineage in melanocortin pharmacology.[1][2]

Mechanism

Melanotan II is the broadest-spectrum melanocortin receptor agonist in the peptide class — binding MC1R, MC3R, MC4R, and MC5R with no significant activity at MC2R (the adrenocortical ACTH receptor). Receptor-specific downstream effects:[1][2]

  • MC1R → melanogenesis. Gαs coupling → adenylyl cyclase → cAMP → PKA → MITF phosphorylation → tyrosinase and related melanogenic enzyme upregulation → shift toward eumelanin production. Visible as skin darkening independent of UV exposure.
  • MC3R / MC4R → appetite and energy homeostasis. Central MC4R signaling is a regulator of food intake; MC3R has complementary metabolic effects.
  • MC4R → sexual function. The MC4R-linked effects on sexual arousal are the basis for the separate FDA approval of bremelanotide (Vyleesi) for hypoactive sexual desire disorder.
  • MC5R → exocrine / sebaceous. Less well characterized; implicated in sebaceous gland and immune modulation.

Pharmacokinetics

  • Plasma half-life (SC). Approximately 33 minutes — substantially longer than endogenous α-MSH (seconds) due to cyclization and D-amino-acid substitution that resist proteolytic degradation.[1]
  • Effect duration. Hours to days because melanogenesis is a transcriptional cascade that outlives plasma drug exposure. Visible pigmentation changes have been reported within 5–7 days at doses as low as 0.01 mg/kg in clinical trials.[1]
  • Metabolism. Peptidase-mediated; renal clearance predominates.

Documented safety signals

The dermatology and case-report literature has documented the following safety signals in Melanotan II users. These are educational notes, not comprehensive safety guidance:

  • Atypical melanocytic nevi. Appearance of new atypical nevi and rapid darkening or enlargement of pre-existing nevi. Because MT-II activates MC1R broadly — including in potentially atypical melanocytes — dermatologic surveillance is the published-literature precaution.
  • Rhabdomyolysis. Case reports in the literature.
  • Priapism. Related to MC4R-mediated sexual-arousal effects; documented in clinical and case literature.
  • Gastrointestinal effects. Nausea, flushing, and spontaneous yawning are commonly reported with melanocortin agonists in the class.

Regulatory status

  • FDA approval: None.
  • April 15, 2026 503A update: Melanotan II was listed for removal from Category 2 as one of twelve peptide bulk drug substances affected by the update.[3] PCAC review is required for inclusion on the 503A bulks list.
  • Europe: Melanotan I (afamelanotide, Scenesse) — a distinct molecule — is approved by the European Medicines Agency for erythropoietic protoporphyria. Melanotan II is not approved by the EMA.
  • Related FDA-approved drug: Bremelanotide (Vyleesi, AMAG Pharmaceuticals) is approved for hypoactive sexual desire disorder in premenopausal women. Bremelanotide and Melanotan II are distinct peptides with different receptor selectivity profiles.

Storage and handling

  • Lyophilized powder. Store sealed per supplier instructions — typically refrigerated at 2–8 °C or frozen at −20 °C.
  • After reconstitution. Refrigerate at 2–8 °C. Bacteriostatic water (0.9% benzyl alcohol) for multi-draw use; sterile water for single-draw.
  • Handling. Swirl to mix. Avoid freeze–thaw. Discard cloudy or discolored solutions.

Reconstitution math

Math only — no dose recommendation. Concentration after reconstitution determines how many insulin-syringe units equal a given mcg amount.

Example 1 · 10 mg vial + 2 mL bac water concentration = 10 mg / 2 mL = 5 mg/mL = 5000 mcg/mL
1 unit = 0.01 mL = 50 mcg
→ 250 mcg = 5 units
→ 500 mcg = 10 units
→ 1 mg = 20 units
→ 5 mg = 100 units (full syringe)
Example 2 · 10 mg vial + 1 mL bac water concentration = 10 mg / 1 mL = 10 mg/mL = 10,000 mcg/mL
1 unit = 0.01 mL = 100 mcg = 0.1 mg
→ 250 mcg = 2.5 units
→ 500 mcg = 5 units
→ 1 mg = 10 units
→ 10 mg = 100 units (full syringe)
Example 3 · 10 mg vial + 5 mL bac water concentration = 10 mg / 5 mL = 2 mg/mL = 2000 mcg/mL
1 unit = 0.01 mL = 20 mcg
→ 100 mcg = 5 units
→ 500 mcg = 25 units
→ 1 mg = 50 units
→ 2 mg = 100 units (full syringe)

Frequently asked questions

What is Melanotan II?

Synthetic cyclic heptapeptide α-MSH analog. Broad-spectrum melanocortin agonist. Developed at University of Arizona in the 1980s.[1]

How does it work?

Agonizes MC1R/3R/4R/5R. MC1R → melanogenesis (UV-independent tanning). MC4R → appetite + sexual arousal. MC5R → sebaceous.[1][2]

What's the half-life?

~33 min plasma SC. Effects last hours-days via downstream signaling cascades.[1]

How do I reconstitute a 10 mg vial?

Typical: 10 mg + 2 mL bac water = 5 mg/mL → 1 unit = 50 mcg; 500 mcg = 10 units. Using 1 mL doubles concentration.

Is it FDA-approved?

No. April 15, 2026 503A Category 2 removal.[3] Related drug bremelanotide (Vyleesi) IS FDA-approved for HSDD — distinct molecule.

What are the safety signals?

Atypical nevi, rapid darkening of existing nevi, rhabdomyolysis case reports, priapism, nausea, flushing, spontaneous yawning.

Primary references

  1. Hruby VJ, Wilkes BC, Hadley ME, et al. α-Melanotropin: the minimal active sequence and analogues; melanotan II development. University of Arizona foundational work, 1980s. Summarized in peer-reviewed melanocortin pharmacology reviews.
  2. Tao YX. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr Rev, 2010 (PMC3365848). PMC3365848
  3. U.S. Food and Drug Administration. 503A Categories Update for April 2026 — notice that Melanotan II was listed for removal from Category 2 as one of twelve peptide bulk drug substances affected. fda.gov/media/94155
  4. Clayton AH, Althof SE, Kingsberg S, et al. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. (For context on the related MC4R-selective peptide bremelanotide / Vyleesi, which is separately FDA-approved.)
  5. Böhm M, Luger T. An overview of benefits and risks of chronic melanocortin-1 receptor activation. J Eur Acad Dermatol Venereol, 2025. JEADV

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