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Melanotan II

From PeptidePlaza, the free peptide reference · Entry #020 · Nootropic · Hand-curated entry · Editorial standards

Research warning. For educational reference only. Non-selective MC receptor activation produces a broad side-effect profile. Long-term melanocyte stimulation has unknown effects on melanoma risk. Not FDA-approved.

Melanotan II (also known as MT-2, MT-II) is a nootropic research peptide. A potent cyclic analog of α-MSH that activates melanocortin receptors broadly. Studied for UV-independent melanogenesis, appetite suppression, and as the parent compound of PT-141 (Bremelanotide).

Melanotan II is a cyclic synthetic analog of alpha-melanocyte stimulating hormone (α-MSH) with a D-Phe substitution at position 7 and a lactam bridge. It is a non-selective melanocortin receptor agonist (MC1R–MC5R). Research encompasses: melanogenesis via MC1R without UV exposure, appetite suppression and metabolic effects via MC3R/MC4R, arousal via hypothalamic MC4R (basis of its metabolite PT-141/Bremelanotide), and reduced alcohol and compulsive behaviour in animal models. Due to its non-selectivity and potency, it has a broader side-effect profile than selective analogs.

1 Mechanism of action

Non-selective agonism at MC1R (melanogenesis), MC3R (energy homeostasis), MC4R (appetite/arousal/CNS), MC5R (exocrine glands). Stimulates melanocyte dendrite elongation and eumelanin synthesis independent of UV radiation.

Primary targets: MC1R · MC3R · MC4R · MC5R

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • UV-independent melanogenesis via MC1R activation
  • Appetite suppression and ethanol intake reduction
  • Parent compound for PT-141 development

2.2 Side effects

  • Nausea and facial flushing
  • Spontaneous arousal (CNS-mediated)
  • Darkening of pre-existing nevi and freckles

3 Chemical and physical properties

CAS number121062-08-6
Molar mass1024.17 g/mol
Purity (typical)>99.0%
Half-life~1–2 hours
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsMC1R, MC3R, MC4R, MC5R

3.1 Amino acid sequence

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH (cyclic lactam)

4 Research dosages

0.25–1.0 mg SC 2–3x weekly for melanogenesis research; lower doses (0.1 mg) for appetite studies.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Melanotan II: A Melanotropic Peptide That Induces Penile Erection
    Life Sciences (1996) · Preclinical · N=28 (rats)
    First description of MT-II CNS-mediated arousal effects in animal models; identified basis for what became PT-141/Bremelanotide development.
    Key finding: MT-II induced spontaneous penile erection via CNS melanocortin receptors — basis for eventual PT-141 development.
  2. Melanotan-II Reduces Ethanol and Fat Intake in Rodent Models
    Psychopharmacology (2003) · Preclinical · N=40 (rats)
    MT-II administration reduced voluntary ethanol intake and high-fat diet consumption in rats; MC4R identified as key mediator of appetite suppression.
    Key finding: MT-II reduced ethanol intake by 40–60% and high-fat food consumption — MC4R identified as mediator of both effects.
  3. Changes in Oral Mucosa Associated with Melanotan II Injections: A Case Report
    Life (Basel, Switzerland) (2026) · Preclinical
    To date, there is a lack of published data specifically addressing the timeline for resolution of oral pigmentation associated with Melanotan II use, making this case a valuable contribution to the limited existing literature on the subject.
  4. Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma?
    International journal of oral and maxillofacial surgery (2025) · Preclinical
    This report highlights the need for awareness of the possible serious side effects associated with Melanotan II nasal spray.
  5. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress
    European journal of pharmacology (2024) · Preclinical
    The results support the argument that ACTH(4-10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.
  6. 5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II
    Chemistry (Weinheim an der Bergstrasse, Germany) (2024) · Review
    Both classes of stapled peptides show nanomolar Ki's, with one showing a sub-nanomolar Ki value.
  7. Melanotan-II reverses memory impairment induced by a short-term HF diet
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2023) · Preclinical
    This study provides evidence that even a short-term HF diet has an impact on memory and emotions and is the first study to show that MT-II reverses these changes.
  8. Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food
    Neuropeptides (2022) · Preclinical
    NAcc that is selective for appetite and satiety without affecting metabolism or producing an aversive state.

6 Safety and risk profile

6.1 Regulatory status

Melanotan II is currently classified as Not approved. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 25/100 — high concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • History of melanoma or dysplastic nevi
  • Uncontrolled hypertension
  • Pregnancy (teratogenicity unknown)
  • Active autoimmune conditions affecting skin

6.3 Drug interactions

Drug or classInteractionRisk
Photosensitizing medications (tetracyclines, retinoids)Additive melanogenesis — excessive pigmentation risk.Moderate
AntihypertensivesMC receptor activation can increase blood pressure transiently — monitor in hypertensive subjects.Moderate

6.4 Long-term risks

  • Unknown melanoma risk from chronic MC1R hyperstimulation
  • Irreversible hyperpigmentation of sun-exposed areas and scars
  • Nevus changes requiring dermatological monitoring
  • Potential for melanocortin receptor desensitization

6.5 Research best practices

  • Store at −20 °C; protect from light
  • Start with micro-doses (50–100 μg) to assess nausea sensitivity
  • Dermatological monitoring of moles recommended in any protocol
  • Avoid concurrent UV exposure until pigment stabilizes
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

How does Melanotan II induce tanning?
By activating MC1R receptors on melanocytes, Melanotan II stimulates eumelanin (dark pigment) production independent of UV exposure. This results in darkening of skin without the DNA damage caused by UV radiation — though the pigment is not a substitute for sun protection.
What are the main side-effect concerns?
Melanotan II is non-selective, stimulating all five melanocortin receptors. This creates a broad profile: nausea and flushing (common), spontaneous arousal (MC4R), darkening of moles/freckles (MC1R), and appetite suppression. Its non-selectivity limits therapeutic utility compared to selective analogs like PT-141 or setmelanotide.

8 References

  1. Changes in Oral Mucosa Associated with Melanotan II Injections: A Case Report PubMed (2026). Bonchev A, et al.. View source
  2. Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma? PubMed (2025). Yassin Alsabbagh A, et al.. View source
  3. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress PubMed (2024). Inozemtseva LS, et al.. View source
  4. 5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II PubMed (2024). Todorovic M, et al.. View source

Related compounds

Entries that share a target, a mechanism, or a research area with Melanotan II.

PT-141approved

Also targets MC1R

A cyclic heptapeptide melanocortin receptor agonist and active metabolite of Melanotan II. Unlike peripheral vasodilators, PT-141 acts centrally via the CNS to modulate arousal and food intake pathways.

Semaxnootropic

Also targets MC4R

A synthetic analog of a fragment of ACTH that lacks hormonal activity but retains potent neuroprotective and cognitive-enhancing properties. Widely used in Russian clinical settings for stroke, memory, and attention disorders.

Survodutidemetabolic

Shares agonism and energy pharmacology

A 29-amino-acid dual agonist that pairs GLP-1 appetite suppression with glucagon-driven energy expenditure and hepatic fat oxidation. Its liver-fat data is the standout: up to 63% reduction.

Setmelanotideapproved

Shares mc4r and mc1r pharmacology

A cyclic octapeptide that restores signalling in a broken melanocortin pathway. The only obesity drug that treats a specific genetic lesion rather than appetite in general.

Vasoactive Intestinal Peptidenootropic

Also nootropic

Vasoactive Intestinal Peptide (VIP) is a neuropeptide that activates VIP receptor 1 (VPR1) and VIP receptor 2 (VPR2), which are G protein-coupled receptors.

GHK-Cuanti-aging

Shares synthesis and stimulates pharmacology

A naturally occurring tripeptide-copper complex found in human plasma, saliva, and urine. Plasma levels decline sharply with age. Extensively studied for collagen induction, skin remodeling, and gene expression regulation.

9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.

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