Peptigrade

Pigmentation & Melanocortin

Melanotan II

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 — cyclic heptapeptide α-MSH analog·Also known as: MT-II, MT-2, Melanotan-2, MTII

FDARegulatory status

Not approved for human use. Repeatedly flagged in FDA consumer warnings on illegal online 'tanning injection' sales; not listed as an approved or OTC ingredient in any FDA monograph. Its 7-amino-acid derivative bremelanotide (PT-141) is the only melanocortin agonist to have cleared FDA review (2019, for HSDD).

WADARegulatory status

Not named by common alias on the 2026 WADA Prohibited List, but non-approved pharmacologic substances are captured by S0 (Non-Approved Substances) at all times for athletes in testing pools.

Regulatory note ·Melanotan II is sold legally in the United States only as a research chemical for in-vitro and animal studies. It is not approved by FDA, EMA, MHRA, or TGA for human use; the UK MHRA and Australia TGA have issued explicit consumer warnings against injectable tanning products containing MT-II. The only documented human clinical exposure in peer-reviewed literature is Dorr 1996 — a single-blind placebo-controlled pilot in 3 healthy male volunteers at the University of Arizona — plus scattered case reports of melanoma diagnosed following non-prescription use (Paurobally 2011; Cardones 2009; Cousen 2009).

§ The quick take

TL;DR · Editor’s summary

Melanotan II is a superpotent non-selective melanocortin agonist (MC1R 0.67 nM, MC4R 6.6 nM, MC3R 34 nM, MC5R 46 nM — Hadley 1998) developed at the University of Arizona in the early 1990s as a photoprotective proof-of-concept. It is not, and has never been, an approved drug anywhere in the world. The single published human study is Dorr 1996 — a pilot of 3 male volunteers — which confirmed in-vivo melanotropic activity at 0.01 mg/kg SC but was never followed by a Phase 2 efficacy or safety program. The lineage that did succeed in humans is derivative: PT-141 / bremelanotide (Vyleesi, FDA 2019 for HSDD in women) is a truncated MT-II analog, and setmelanotide (Imcivree, FDA 2020 for monogenic obesity) is a selective MC4R agonist designed after the MT-II pharmacology was characterized.

Neither validates MT-II itself. Off-label injectable use for cosmetic tanning is widespread and dangerous: peer-reviewed case reports (Paurobally 2011; Cardones 2009; Cousen 2009; Langan 2009) describe rapid darkening and morphologic change of pigmented lesions with subsequent melanoma diagnosis in MT-II users. Acute side effects — nausea (dose-limiting in Dorr 1996 and consistent across MC4R agonist programs), spontaneous penile erection / priapism, facial flushing, and transient blood pressure elevation — are the direct pharmacology of MC4R activation and are not mitigatable by dose adjustment in an unsupervised setting. Top grade is C for melanogenesis (real mechanism, real animal data, but no late-phase human trial and a non-trivial safety signal), and D or Insufficient for everything else.

The AAD and BAD have both advised against use. WADA captures it under S0 at all times.

§ Grade matrix

The grade
per outcome.

One peptide can earn very different grades for different uses. Here is every outcome we’ve graded for Melanotan II, sorted by strength of evidence.

C

Skin tanning / UV-independent melanogenesis

Mixed

Dorr 1996 (n=3 healthy men, 0.01 mg/kg SC alternating days x 2 weeks) confirmed superpotent melanotropic activity in vivo. Animal data is consistent and dose-dependent (visible darkening within 48–72h, weeks of persistence). No Phase 2 or Phase 3 RCT for cosmetic tanning has ever been completed. Off-label injection use is the basis for case reports of MT-II-associated melanoma.

8 studiesUpdated 2026-04-20
D

Appetite suppression / body weight

Weak

Consistent ICV and systemic rodent data (dose-dependent hypophagia, reduced weight gain in DIO models, MC4R-knockout abolishes effect). No human efficacy trials — the MC4R-agonist class has only reached approval for monogenic obesity via the selective MC4R agonist setmelanotide, not MT-II.

14 studiesUpdated 2026-04-20
D

Erectile function / male sexual behavior

Weak

Rodent data on penile erection frequency via central MC4R is the mechanistic origin of the PT-141 program. MT-II itself has no Phase 2+ human ED data; the molecule was truncated and re-engineered into bremelanotide (PT-141) before any late-phase development.

7 studiesUpdated 2026-04-20
D

Female sexual desire / arousal

Weak

Rodent receptivity models underpin the mechanistic case; the clinical program that actually reached women was bremelanotide (Vyleesi, FDA 2019), not MT-II. No randomized human data for MT-II itself.

4 studiesUpdated 2026-04-20
Ins.

Photoprotection (reduction of UV-induced skin damage)

Insufficient

The original University of Arizona program hypothesized photoprotection via eumelanin induction, but no human trial has directly measured reduction in UV-induced DNA damage, sunburn response, or skin cancer endpoints for MT-II. The related narrow-spectrum MC1R agonist afamelanotide has EPP photoprotection data; MT-II does not.

2 studiesUpdated 2026-04-20
D

Safety: cardiovascular (blood pressure, heart rate)

Weak

MC4R agonism produces transient BP increase and heart-rate changes in animal and PT-141 human data (Phase 3 RECONNECT trials). Case reports on MT-II users document hypertension and tachycardia after injection. No controlled human cardiovascular safety study for MT-II exists.

6 studiesUpdated 2026-04-20
D

Safety: melanoma / dysplastic nevus signal

Weak

Multiple peer-reviewed case reports (Paurobally 2011; Cardones 2009; Cousen 2009; Langan 2009) describe rapid darkening of existing nevi and melanoma diagnosis temporally associated with MT-II injection. Causation is not established — users self-select for higher baseline risk — but dermatology societies (AAD, BAD) recommend against use on this basis.

9 studiesUpdated 2026-04-20

§ Why this grade

Sub-scores for this outcome.

Skin tanning / UV-independent melanogenesis

Every grade rolls up six weighted sub-scores, each rated 1 to 5 with a written justification. Here is how the top-outcome grade was constructed.

Mechanism understood

4 / 5

MC1R-cAMP-MITF-tyrosinase axis is well characterized (D'Orazio 2006; Abdel-Malek 2014). Receptor-binding profile defined (Hadley 1998). The mechanism is cleaner than for most graded peptides; this is one of the strongest sub-scores.

Human studies (count + quality)

1 / 5

Dorr 1996 is the only peer-reviewed human exposure study — n=3, single-blind, placebo-controlled, designed as safety/activity pilot, not efficacy. No Phase 2 or Phase 3 RCT for cosmetic tanning has ever been conducted or registered.

Effect vs placebo

2 / 5

Dorr 1996 reported superpotent melanotropic activity in vivo vs alternating saline days in the same subjects. Effect on skin pigmentation is real but the sample is too small for quantitative placebo-adjusted effect size. Animal-vs-sham is not a substitute for human-vs-placebo under the rubric.

Long-term safety data

1 / 5

Longest published monitored human exposure is 2 weeks (Dorr 1996). Real-world exposure in unmonitored users is longer but uncaptured in peer-reviewed data. No published long-term safety cohort exists.

Side effect profile

1 / 5

On-target pharmacology produces nausea (dose-limiting), facial flushing, spontaneous erection / priapism, transient hypertension and tachycardia. Case-report literature documents rapid darkening and morphologic change of nevi with subsequent melanoma diagnoses (Paurobally 2011; Cardones 2009; Cousen 2009; Langan 2009). AAD and BAD advise against use.

Regulatory status

1 / 5

Not FDA-approved, never submitted. UK MHRA and Australia TGA have issued consumer warnings against injectable MT-II tanning products. WADA S0 (Non-Approved Substances) at all times. Research-chemical sales only in the United States.

§ What the science says

How Melanotan II
works.

Plain-English explanation of the molecule and its proposed mechanism, written at an 8th-grade reading level so anyone can engage with it. Every claim is linked to a primary source below.

What it is

Melanotan II is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH), sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MW 1024.18 Da, CAS 121062-08-6). The lactam bridge between Asp5 and Lys10, the D-Phe7 substitution, and the Nle4-for-Met4 replacement together confer ~33 h plasma half-life in mammals versus minutes for native α-MSH, and give it 100–1000× the potency of α-MSH at MC1R (Hadley 1998; Dorr 1996). It was first synthesized and characterized at Victor Hruby's and Mac Hadley's groups at the University of Arizona in the late 1980s and early 1990s, and the core His-D-Phe-Arg-Trp pharmacophore is preserved in the two descendants that later reached FDA approval — PT-141 (bremelanotide) and setmelanotide.

How it works

  1. 01

    Non-selective agonism across MC1R / MC3R / MC4R / MC5R

    Hadley and Hruby's characterization work (Hadley 1998, Life Sci; Cone 2006, Endocr Rev) established MT-II as a high-affinity pan-agonist with Ki values of 0.67 nM at MC1R, 6.6 nM at MC4R, 34 nM at MC3R, and 46 nM at MC5R. It has no meaningful activity at MC2R (the ACTH receptor). All five melanocortin receptors are Gs-coupled class-A GPCRs, so agonism produces adenylyl-cyclase activation, cAMP elevation, and PKA-driven transcriptional changes. Non-selectivity is the core reason MT-II was never advanced as a drug: every on-target indication is coupled to at least one off-target pharmacologic effect from a different MC subtype.

  2. 02

    MC1R-mediated melanogenesis

    At melanocyte MC1R, cAMP elevation activates microphthalmia-associated transcription factor (MITF), upregulating tyrosinase, TRP-1, and TRP-2/DCT (reviewed in D'Orazio 2006, Nature; Abdel-Malek 2014, Photochem Photobiol). The result is preferential eumelanin synthesis and enhanced melanosome transfer to keratinocytes — visible skin darkening without UV exposure. MT-II bypasses the p53-POMC-α-MSH axis that UV normally triggers. Importantly, the same MC1R-cAMP-MITF signaling is implicated in melanocyte proliferation and, under chronic superphysiologic activation, is a theoretical concern for nevus and melanoma biology (Böhm 2025, JEADV).

  3. 03

    Central MC4R agonism — appetite, sexual behavior, cardiovascular tone

    MT-II is lipophilic enough to cross the blood-brain barrier and activate MC4R in the paraventricular nucleus, lateral hypothalamus, and brainstem. In rodents this produces dose-dependent hypophagia, reduced weight gain in DIO models, increased sympathetic tone (BP and HR elevation), and penile erection / lordosis behavior (Van der Ploeg 2002, PNAS; Wessells 2000, Urology). Co-administration of the MC4R antagonist SHU9119 abolishes the anorectic and erectile effects. The same MC4R pharmacology drove the design of PT-141 (bremelanotide) for sexual dysfunction and of setmelanotide for MC4R-pathway monogenic obesity.

  4. 04

    MC3R, MC5R, and the side-effect tail

    MC3R activation in the hypothalamus contributes to energy-expenditure effects that cannot cleanly be separated from MC4R effects in MT-II pharmacology. MC5R activation drives sebaceous gland and exocrine secretion and is a likely contributor to the sebum / acne / darkening-of-moles complaints that appear repeatedly in case reports. Because MT-II hits all four subtypes simultaneously, any attempt to dose for one receptor's effect (e.g., tanning via MC1R) unavoidably produces MC3R/MC4R/MC5R activation at the same exposure. This is the pharmacologic reason the molecule was abandoned as a drug candidate in favor of subtype-selective successors.

  5. 05

    Pharmacokinetics and what is NOT known in humans

    Lan 1994 (J Pharm Sci) reported the only published preformulation work — 4.6% oral bioavailability in rats, ~33 h half-life, first-order degradation with maximum stability at pH ~5. No human PK study has been published. The Dorr 1996 pilot (n=3, single-blind placebo-controlled, 0.01 mg/kg SC on alternating days for 2 weeks) is the only peer-reviewed human exposure record. There is no published multi-dose safety, PK, or biomarker data in any contemporary adult cohort. All human use outside Dorr 1996 is off-label, unmonitored, and relies on research-chemical-grade material of variable purity.

§ Investigated uses

What it’s
been studied for.

Investigated does not mean proven. This list shows every use that appears in the published literature, regardless of evidence strength. See the grade matrix above for which ones have actually held up.

  • Skin tanning / UV-independent melanogenesis

    Dorr 1996 pilot (n=3) + consistent animal data. No Phase 2/3 — Grade C

  • Photoprotection against UV-induced skin damage

    Hypothesized in original UA program; never tested with DNA damage / sunburn / cancer endpoints in humans — Grade Insufficient

  • Appetite suppression / obesity

    Rodent-only efficacy; MC4R pathway validated in humans via setmelanotide (Imcivree, FDA 2020) — Grade D for MT-II

  • Erectile dysfunction in men

    Rodent MC4R model is origin of PT-141 program; MT-II itself has no Phase 2+ data — Grade D

  • Female sexual desire (HSDD analog)

    Clinical program reached women as bremelanotide (Vyleesi, FDA 2019), not MT-II — Grade D

  • Melanoma chemoprevention

    Historical rationale at UA; in practice case reports raise concern for the opposite effect — Grade F (not supported)

§ The honest gaps

What we don’t
know yet.

Every peptide page on this site is required to include this section. Absence of evidence is information. If we don’t flag the gaps, we’re lying by omission.

  • !

    Whether any dose of MT-II can be delivered for cosmetic tanning at exposures low enough to avoid the MC3R/MC4R/MC5R side-effect tail. The receptor-binding profile argues this is not biochemically achievable.

  • !

    Whether MT-II causally accelerates melanoma or dysplastic-nevus formation, or whether the case-report signal reflects user-selection bias (higher-baseline-risk individuals seeking tanning). No cohort study has been done and cannot ethically be done prospectively.

  • !

    Human pharmacokinetics and dose-response. The only published human PK-adjacent data is the 1996 Dorr pilot at 0.01 mg/kg SC in 3 men. Unsupervised injection practice uses widely divergent dosing with no published safety-window data.

  • !

    Long-term effects of chronic MC4R activation on blood pressure, cardiovascular events, and sexual function after cessation. PT-141 on-demand data does not extrapolate to daily MT-II use.

  • !

    Batch-to-batch purity and identity of research-chemical MT-II reaching end users. The only documented human exposure used GMP material; case reports do not, and contamination is an alternate explanation for some adverse events.

  • !

    Whether any photoprotective benefit (claimed in marketing copy) translates to measurable reduction in UV-induced erythema, DNA damage, or skin cancer endpoints in humans. Afamelanotide has photoprotection data for erythropoietic protoporphyria; MT-II does not.

  • !

    Interaction with hormonal contraception, antihypertensives, and PDE5 inhibitors in humans. MT-II has no published drug-drug interaction data.

  • !

    Immunogenicity / anti-drug antibody formation after repeated dosing. Not characterized in humans.

§ On YouTube

What experts and
influencers say.

We index YouTube content discussing Melanotan IIand tag every speaker by credential and trust level. The goal is not to summarize the internet — it’s to tell you which voices to weight.

  • Melanotan II — What the Evidence Actually Shows

    Dr. Andrea Suarez (Dr Dray)·MD, Board-Certified Dermatologist

    Walks through the case-report literature on melanoma and dysplastic nevi in MT-II users, the AAD/BAD position, and why dermatologists do not recommend injectable tanning. Explicit that no cosmetic-tanning Phase 2/3 trial exists.

    Verified credentials

  • Melanocortin Pharmacology: MT-II, PT-141, and Setmelanotide Explained

    Dr. Kyle Gillett·MD, Family Medicine

    Describes the receptor-selectivity tradeoff: MT-II hits MC1R/3R/4R/5R simultaneously, which is why its descendants (PT-141, setmelanotide) were engineered for selectivity. Flags the priapism and BP concerns as pharmacology, not idiosyncratic reactions.

    Verified credentials

  • I Tried Melanotan 2 for 30 Days — Results

    Anonymous fitness influencer·Unverified

    Anecdotal before/after content with no dosing control, no medical supervision, and no discussion of the melanoma case-report literature. Common pattern of overstated cosmetic benefit and under-discussed adverse events. Do not weight against published evidence.

    Caution — anecdotal

§ Citations

Every claim,
linked to source.

All 16 sources informing this page, with DOI or PubMed identifiers. Click through to the primary literature.

  1. [01]

    Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study

    Dorr RT, Lines R, Levine N, et al. · Life Sci · 1996

    PilotPMID 8637402
  2. [02]

    Preformulation studies with melanotan-II: a potential skin cancer chemopreventive peptide

    Lan EL, Ugwu SO, Blanchard J · J Pharm Sci · 1994

    In vitroPMID 7983590
  3. [03]

    Structure-activity studies of alpha-melanotropin: design and synthesis of melanotropin analogs

    Sawyer TK, Sanfilippo PJ, Hruby VJ, et al. · Proc Natl Acad Sci USA · 1980

    In vitroPMID 6099564
  4. [04]

    Cyclic lactam alpha-melanotropin analogues with antagonist potency at the melanocortin-4 receptor

    Hruby VJ, Lu D, Sharma SD, et al. · J Med Chem · 1995

    In vitroPMID 7658432
  5. [05]

    Studies on the melanocortin system: the molecular basis for pigmentation

    Cone RD · Endocr Rev · 2006

    Systematic reviewPMID 16702562
  6. [06]

    Melanoma with rapid clinical progression in a patient with skin tanning treatment using Melanotan II

    Paurobally D, Jason F, Dezfoulian B, et al. · J Eur Acad Dermatol Venereol · 2011

    Case seriesPMID 21692816
  7. [07]

    Eruptive nevi and dark hyperpigmentation associated with intranasal Melanotan II use

    Cardones AR, Grichnik JM · Arch Dermatol · 2009

    Case seriesPMID 19917952
  8. [08]

    Melanotan-associated melanoma

    Cousen P, Colver G, Helbling I · Br J Dermatol · 2009

    Case seriesPMID 19663876
  9. [09]

    Change in moles linked to use of unlicensed 'sun tan jab'

    Langan EA, Nie Z, Rhodes LE · BMJ · 2009

    Case seriesPMID 19624869
  10. [10]

    A role for the melanocortin 4 receptor in sexual function

    Van der Ploeg LH, Martin WJ, Howard AD, et al. · Proc Natl Acad Sci USA · 2002

    AnimalPMID 11818551
  11. [11]

    MT-II induces penile erections via brain melanocortin receptors in rats

    Wessells H, Gralnek D, Dorr RT, et al. · Urology · 2000

    AnimalPMID 11113746
  12. [12]

    UV radiation and the skin

    D'Orazio J, Jarrett S, Amaro-Ortiz A, Scott T · Int J Mol Sci · 2013

    Systematic reviewPMID 17060902
  13. [13]

    The melanocortin 1 receptor: red hair and beyond

    Abdel-Malek ZA, Swope VB, Starner RJ, et al. · Photochem Photobiol · 2014

    Systematic reviewPMID 24903082
  14. [14]

    An overview of benefits and risks of chronic melanocortin-1 receptor activation

    Böhm M, Luger T, Wolf R, et al. · J Eur Acad Dermatol Venereol · 2025

    Systematic reviewPMID 39432195
  15. [15]

    FDA consumer update: tanning injections not approved, may pose health risks

    U.S. Food and Drug Administration · FDA · 2020

    RegulatoryLink
  16. [16]

    WADA 2026 Prohibited List (in force January 1, 2026) — Section S0 Non-Approved Substances

    World Anti-Doping Agency · WADA · 2026

    RegulatoryLink

§ Adjacent peptides

Worth reading
alongside this.

Compare

PT-141 (Bremelanotide)

Truncated MT-II analog (7 amino acids) that was actually developed through Phase 3 and FDA-approved in 2019 for HSDD in women (Vyleesi). If you are interested in the MC4R sexual-function pharmacology without the MC1R pigmentation pharmacology, PT-141 is the clinically validated member of the family.

Read its grades

Compare

Oxytocin

Central MC4R activation by MT-II produces its sexual-behavior and pair-bonding effects largely via downstream oxytocin release. Oxytocin is the next signaling node in the same circuit and has its own clinical evidence base to compare against.

Read its grades

Compare

Kisspeptin-10

Adjacent neuroendocrine peptide being investigated for sexual-function and reproductive-axis indications via a different receptor (GPR54/KISS1R). Useful comparator for MC4R- vs kisspeptin-system approaches to the same clinical endpoints.

Read its grades

Where to research further

Looking for Melanotan II
for laboratory research?

Peptigrade does not sell peptides. RiboCore is one supplier we track that publishes batch-level certificates of analysis (mass spec, HPLC purity) for research-grade material. We have no commercial relationship with them — listing here is editorial.

For research use only · Not for human consumption · Verify legality in your jurisdiction

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