Peptide profile
Melanotan II
Potent tanning and libido melanocortin agonist · also known as MT-II, MT2, Melanotan 2
Compare Melanotan II with other peptides →Summary
Melanotan II (MT-II) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (α-MSH) originally developed at the University of Arizona. It potently activates melanocortin receptors to stimulate skin tanning, increase sexual arousal, and suppress appetite. Unlike natural α-MSH, its cyclic structure confers greater receptor affinity and metabolic stability.
- Typical dose
- 250–500 mcg/day (loading); 100–250 mcg/day (maintenance)
- Half-life
- ~30–60 minutes (terminal elimination ~1–2 hours)
- Route
- Subcutaneous, Intramuscular, Nasal
- Cycle length
- 4–8 weeks loading, then as-needed maintenance
Mechanism
How it works
MT-II acts as a non-selective agonist at melanocortin receptors MC1R, MC3R, MC4R, and MC5R. Activation of MC1R on melanocytes upregulates cAMP production via Gs protein coupling, driving tyrosinase activity and eumelanin synthesis for UV-independent skin darkening. Simultaneous MC4R activation in hypothalamic nuclei mediates appetite suppression and pro-erectile signaling through downstream nitric oxide pathways.
Reported in research
Benefits
- Stimulates eumelanin production, producing a deep, natural-looking tan without prolonged UV exposure
- Activates MC4R pathways to promote penile erection and enhance libido in both sexes
- Suppresses appetite via hypothalamic melanocortin signaling, supporting fat loss and caloric deficit
- Increased skin pigmentation may provide modest photoprotection against UV-induced DNA damage
Context, not a prescription
Dosing
- Typical range
- 250–500 mcg/day (loading); 100–250 mcg/day (maintenance) (Subcutaneous, Intramuscular, Nasal)
- Cycle length
- 4–8 weeks loading, then as-needed maintenance
- Half-life
- ~30–60 minutes (terminal elimination ~1–2 hours)
Safety
Side effects & contraindications
Possible side effects
- Nausea and facial flushing, especially at higher doses or after rapid dose escalation
- Spontaneous erections (priapism risk at high doses)
- Darkening or growth of pre-existing moles (nevi)
- Fatigue and yawning shortly after injection
- Hyperpigmentation of freckles and skin lesions
- Increased blood pressure transiently post-injection
- Decreased appetite and potential unwanted weight loss
Contraindications
- Personal or family history of melanoma or dysplastic nevus syndrome
- Pregnancy or breastfeeding due to unknown fetal safety profile
- Cardiovascular disease or uncontrolled hypertension
- History of priapism or conditions predisposing to prolonged erection
- Concurrent use of vasodilators or PDE5 inhibitors without medical supervision
Research information, not medical advice. Always consult a licensed clinician before considering any peptide.
In depth
Full profile
What it does
Users typically notice darker skin tone, increased sexual thoughts or spontaneous erections, reduced appetite, and occasional yawning or fatigue shortly after dosing.
How it works
Imagine your body's melanocortin receptors as locks on different doors — one door controls skin color, another controls appetite, and another controls sexual arousal. Melanotan II is like a master key that opens all these doors simultaneously, whereas your body's natural hormone only fits some of them.
After injection, MT-II travels through the bloodstream and binds to receptors in the skin (causing tanning), in the brain's hypothalamus (reducing hunger and increasing arousal), and in erectile tissue (promoting blood flow). Effects begin within 30–60 minutes of dosing.
What to expect
Nausea and flushing can occur within 30 minutes of injection. Visible tanning typically begins after 3–7 days of dosing, especially with some sun or UV exposure. Libido and erection effects may be noticed within 1–2 hours of a dose.
- Days 1–5: Loading phase. Expect nausea, flushing, fatigue, and possibly spontaneous erections. Start at 250 mcg and adjust. Little visible tanning yet.
- Weeks 1–3: Skin begins to darken noticeably, especially with brief UV exposure. Appetite may decrease. Side effects typically lessen as your body adjusts.
- Weeks 4–8: Tan deepens and may be maintained with lower maintenance doses. Sexual effects remain present. Some users transition to once or twice weekly dosing to hold results.
Good to know
- Always start with a very low dose (100–250 mcg) and increase slowly to assess your tolerance
- Inject in the evening to sleep through the worst nausea and flushing
- Have a dermatologist map your moles before starting and check them regularly
- Never use nasal spray formulations sold online — purity and dosing are unreliable
Staying safe
- Nausea and stomach discomfort, especially at first
- Face and neck flushing (feeling of warmth or redness)
- Spontaneous or prolonged erections
- Feeling tired or yawning after injection
- Existing moles or freckles becoming darker
Avoid if you have:
- People with a personal or family history of skin cancer, especially melanoma
- Pregnant or breastfeeding women
- Anyone with heart disease or high blood pressure
- People taking medications for erectile dysfunction (e.g., Viagra) without doctor supervision
Mechanism of action
Melanotan II is a cyclic lactam analogue of α-MSH with the sequence Ac-Nle4-c[Asp5,D-Phe7,Lys10]-α-MSH4-10-NH2. It binds with high affinity to MC1R (Kd ~1 nM), MC3R, MC4R, and MC5R, functioning as a full agonist at each. At MC1R, Gs-coupled adenylyl cyclase activation elevates intracellular cAMP, phosphorylating and activating microphthalmia-associated transcription factor (MITF), which upregulates tyrosinase, TRP-1, and TRP-2 — the rate-limiting enzymes of eumelanin synthesis. At MC4R in the hypothalamic paraventricular nucleus, activation suppresses NPY/AgRP orexigenic tone and stimulates POMC/CART pathways, reducing food intake. MC4R activation also modulates the sacral parasympathetic outflow and triggers nitric oxide synthase (nNOS) activity in the corpus cavernosum, producing penile erection independent of PDE5 pathways — accounting for its efficacy in psychogenic erectile dysfunction.
Following subcutaneous injection, MT-II has a short plasma half-life of approximately 30–60 minutes due to peptidase activity, but its biological effects (particularly pigmentation) outlast its presence in circulation due to downstream transcriptional changes. Peak plasma concentration is achieved within 30–90 minutes subcutaneously. The peptide crosses the blood-brain barrier poorly in physiological conditions but exerts CNS effects likely via circumventricular organs and median eminence fenestrated capillaries. Hepatic metabolism and renal excretion are the primary clearance routes. Bioavailability via intranasal route is substantially lower (~5–10%) than subcutaneous (~90%), explaining the large dose discrepancy in commercial nasal formulations.
Pharmacodynamics
Nausea mediated by area postrema MC3R/MC4R activation occurs within 20–40 minutes post-injection. Erection effects peak at 1–2 hours. Melanogenic effects require 3–5 days of repeated dosing to produce visible pigmentation, as tyrosinase induction and melanosome maturation are transcriptional processes with inherent lag. Full eumelanin deposition accumulates over 2–4 weeks.
Physiologically: elevated skin L-DOPA and dopaquinone intermediates; increased melanocyte dendricity; upregulation of melanogenic enzyme mRNA. Systemically: transient increases in MAP (5–15 mmHg) via MC4R-mediated sympathetic tone; reduction in ghrelin signaling; increased hypothalamic serotonin release contributing to yawning and fatigue. Long-term: potential shift in mole phenotype from pheomelanin-dominant to eumelanin-dominant expression.
Timeline
- Days 1–3: Peak side effect window. Area postrema MC3R/MC4R activation produces nausea, yawning, flushing. Plasma half-life ~1 hour; no significant melanogenic accumulation yet. MC4R-mediated erections observed.
- Days 4–14: Tyrosinase upregulation measurable at the transcriptional level by day 3–4. Visible melanin deposition begins, enhanced by UV. MITF-driven eumelanin shift in melanosomes. Nausea attenuates via receptor desensitization.
- Weeks 2–8: Mature melanogenesis: sustained tan with melanosome transfer to keratinocytes. Maintenance dosing (100–250 mcg 2–3x/week) sufficient to sustain pigmentation. Appetite suppression persists. Mole surveillance becomes clinically important beyond 4–6 weeks of continuous use.
Comparisons
- Melanotan II — effectiveness High, safety Caution, cost $$, Medium to use
- PT-141 (Bremelanotide) — effectiveness High, safety Moderate, cost $$$, Medium to use
- Afamelanotide (Scenesse) — effectiveness Very High, safety Good, cost $$$$, Low to use
Adverse effects
Common:
- Nausea (incidence ~80% at doses >500 mcg) — mediated by MC3R/MC4R at the area postrema; dose-dependent and diminishing with tachyphylaxis over 5–10 days
- Facial flushing and transient hypertension — adrenergic MC4R-mediated sympathetic activation
- Spontaneous erections lasting 1–4 hours — MC4R/nNOS pathway activation in sacral parasympathetic nuclei
- Hyperpigmentation of melanocytic nevi — MC1R overactivation in existing mole tissue
Rare:
- Priapism (estimated incidence <1% at standard doses, higher with concurrent PDE5 inhibitors) — constitutes a urological emergency
- Melanocytic nevus transformation — case reports of dysplastic changes in pre-existing nevi; causality debated but biologically plausible given MC1R agonism
- Rhabdomyolysis — reported anecdotally with high doses, mechanism unclear
Contraindications & risk mitigation
Contraindicated in:
- Individuals with CDKN2A mutations or familial atypical multiple mole melanoma (FAMMM) syndrome
- Patients on antihypertensives or with labile blood pressure due to transient pressor effects
- Men with anatomical abnormalities predisposing to priapism (sickle cell trait, Peyronie's disease)
- Individuals with autoimmune vitiligo — paradoxical depigmentation responses have been reported
- Baseline and serial full-body dermatological mapping (dermoscopy) every 3 months during use to monitor nevus changes
- Antiemetic pretreatment (e.g., ondansetron 4 mg oral 30 min prior) for first 5–7 injections to manage nausea
- Titrate from 100 mcg and escalate by 100 mcg every 3–5 days; avoid front-loading strategies common in anecdotal protocols
- Avoid concurrent PDE5 inhibitor use due to synergistic hypotensive and priapism risk
- Source only from reputable, third-party tested research suppliers with published HPLC and mass spectrometry COAs
Qué hace
Users typically notice darker skin tone, increased sexual thoughts or spontaneous erections, reduced appetite, and occasional yawning or fatigue shortly after dosing.
Cómo funciona
Imagine your body's melanocortin receptors as locks on different doors — one door controls skin color, another controls appetite, and another controls sexual arousal. Melanotan II is like a master key that opens all these doors simultaneously, whereas your body's natural hormone only fits some of them.
After injection, MT-II travels through the bloodstream and binds to receptors in the skin (causing tanning), in the brain's hypothalamus (reducing hunger and increasing arousal), and in erectile tissue (promoting blood flow). Effects begin within 30–60 minutes of dosing.
Qué esperar
Nausea and flushing can occur within 30 minutes of injection. Visible tanning typically begins after 3–7 days of dosing, especially with some sun or UV exposure. Libido and erection effects may be noticed within 1–2 hours of a dose.
- Days 1–5: Loading phase. Expect nausea, flushing, fatigue, and possibly spontaneous erections. Start at 250 mcg and adjust. Little visible tanning yet.
- Weeks 1–3: Skin begins to darken noticeably, especially with brief UV exposure. Appetite may decrease. Side effects typically lessen as your body adjusts.
- Weeks 4–8: Tan deepens and may be maintained with lower maintenance doses. Sexual effects remain present. Some users transition to once or twice weekly dosing to hold results.
Bueno saber
- Always start with a very low dose (100–250 mcg) and increase slowly to assess your tolerance
- Inject in the evening to sleep through the worst nausea and flushing
- Have a dermatologist map your moles before starting and check them regularly
- Never use nasal spray formulations sold online — purity and dosing are unreliable
Manteniéndose seguro
- Nausea and stomach discomfort, especially at first
- Face and neck flushing (feeling of warmth or redness)
- Spontaneous or prolonged erections
- Feeling tired or yawning after injection
- Existing moles or freckles becoming darker
Evitar si tienes:
- People with a personal or family history of skin cancer, especially melanoma
- Pregnant or breastfeeding women
- Anyone with heart disease or high blood pressure
- People taking medications for erectile dysfunction (e.g., Viagra) without doctor supervision
Mecanismo de acción
Melanotan II is a cyclic lactam analogue of α-MSH with the sequence Ac-Nle4-c[Asp5,D-Phe7,Lys10]-α-MSH4-10-NH2. It binds with high affinity to MC1R (Kd ~1 nM), MC3R, MC4R, and MC5R, functioning as a full agonist at each. At MC1R, Gs-coupled adenylyl cyclase activation elevates intracellular cAMP, phosphorylating and activating microphthalmia-associated transcription factor (MITF), which upregulates tyrosinase, TRP-1, and TRP-2 — the rate-limiting enzymes of eumelanin synthesis. At MC4R in the hypothalamic paraventricular nucleus, activation suppresses NPY/AgRP orexigenic tone and stimulates POMC/CART pathways, reducing food intake. MC4R activation also modulates the sacral parasympathetic outflow and triggers nitric oxide synthase (nNOS) activity in the corpus cavernosum, producing penile erection independent of PDE5 pathways — accounting for its efficacy in psychogenic erectile dysfunction.
Following subcutaneous injection, MT-II has a short plasma half-life of approximately 30–60 minutes due to peptidase activity, but its biological effects (particularly pigmentation) outlast its presence in circulation due to downstream transcriptional changes. Peak plasma concentration is achieved within 30–90 minutes subcutaneously. The peptide crosses the blood-brain barrier poorly in physiological conditions but exerts CNS effects likely via circumventricular organs and median eminence fenestrated capillaries. Hepatic metabolism and renal excretion are the primary clearance routes. Bioavailability via intranasal route is substantially lower (~5–10%) than subcutaneous (~90%), explaining the large dose discrepancy in commercial nasal formulations.
Farmacodinamia
Nausea mediated by area postrema MC3R/MC4R activation occurs within 20–40 minutes post-injection. Erection effects peak at 1–2 hours. Melanogenic effects require 3–5 days of repeated dosing to produce visible pigmentation, as tyrosinase induction and melanosome maturation are transcriptional processes with inherent lag. Full eumelanin deposition accumulates over 2–4 weeks.
Physiologically: elevated skin L-DOPA and dopaquinone intermediates; increased melanocyte dendricity; upregulation of melanogenic enzyme mRNA. Systemically: transient increases in MAP (5–15 mmHg) via MC4R-mediated sympathetic tone; reduction in ghrelin signaling; increased hypothalamic serotonin release contributing to yawning and fatigue. Long-term: potential shift in mole phenotype from pheomelanin-dominant to eumelanin-dominant expression.
Cronología
- Days 1–3: Peak side effect window. Area postrema MC3R/MC4R activation produces nausea, yawning, flushing. Plasma half-life ~1 hour; no significant melanogenic accumulation yet. MC4R-mediated erections observed.
- Days 4–14: Tyrosinase upregulation measurable at the transcriptional level by day 3–4. Visible melanin deposition begins, enhanced by UV. MITF-driven eumelanin shift in melanosomes. Nausea attenuates via receptor desensitization.
- Weeks 2–8: Mature melanogenesis: sustained tan with melanosome transfer to keratinocytes. Maintenance dosing (100–250 mcg 2–3x/week) sufficient to sustain pigmentation. Appetite suppression persists. Mole surveillance becomes clinically important beyond 4–6 weeks of continuous use.
Comparaciones
- Melanotan II — efectividad High, seguridad Caution, costo $$, Medium de usar
- PT-141 (Bremelanotide) — efectividad High, seguridad Moderate, costo $$$, Medium de usar
- Afamelanotide (Scenesse) — efectividad Very High, seguridad Good, costo $$$$, Low de usar
Efectos adversos
Comunes:
- Nausea (incidence ~80% at doses >500 mcg) — mediated by MC3R/MC4R at the area postrema; dose-dependent and diminishing with tachyphylaxis over 5–10 days
- Facial flushing and transient hypertension — adrenergic MC4R-mediated sympathetic activation
- Spontaneous erections lasting 1–4 hours — MC4R/nNOS pathway activation in sacral parasympathetic nuclei
- Hyperpigmentation of melanocytic nevi — MC1R overactivation in existing mole tissue
Raros:
- Priapism (estimated incidence <1% at standard doses, higher with concurrent PDE5 inhibitors) — constitutes a urological emergency
- Melanocytic nevus transformation — case reports of dysplastic changes in pre-existing nevi; causality debated but biologically plausible given MC1R agonism
- Rhabdomyolysis — reported anecdotally with high doses, mechanism unclear
Contraindicaciones y mitigación de riesgos
Contraindicado en:
- Individuals with CDKN2A mutations or familial atypical multiple mole melanoma (FAMMM) syndrome
- Patients on antihypertensives or with labile blood pressure due to transient pressor effects
- Men with anatomical abnormalities predisposing to priapism (sickle cell trait, Peyronie's disease)
- Individuals with autoimmune vitiligo — paradoxical depigmentation responses have been reported
- Baseline and serial full-body dermatological mapping (dermoscopy) every 3 months during use to monitor nevus changes
- Antiemetic pretreatment (e.g., ondansetron 4 mg oral 30 min prior) for first 5–7 injections to manage nausea
- Titrate from 100 mcg and escalate by 100 mcg every 3–5 days; avoid front-loading strategies common in anecdotal protocols
- Avoid concurrent PDE5 inhibitor use due to synergistic hypotensive and priapism risk
- Source only from reputable, third-party tested research suppliers with published HPLC and mass spectrometry COAs
Reference data
Specifications
- Molecular formula
- C50H69N15O9
- Molecular weight
- 1024.18 g/mol
- Half-life
- ~30–60 minutes (terminal elimination ~1–2 hours)
- Route
- Subcutaneous, Intramuscular, Nasal
- Cycle length
- 4–8 weeks loading, then as-needed maintenance
- Storage
- Lyophilized powder: store at 2–8°C (refrigerated), protected from light; stable up to 24 months. Reconstituted solution: store at 2–8°C, use within 28–30 days. Avoid repeated freeze-thaw cycles. Bacteriostatic water recommended for reconstitution.
- Legal status
- Research chemical; not approved by FDA, EMA, or TGA for human therapeutic use. Unscheduled in most jurisdictions but illegal to sell for human consumption in many countries including Australia and the UK.
FAQ
Common questions
Why does MT-II cause erections when it targets melanocortin receptors?
MC4R is densely expressed in the paraventricular nucleus of the hypothalamus and in sacral spinal cord parasympathetic preganglionic neurons. Agonism activates neuronal nitric oxide synthase (nNOS) in the corpus cavernosum via descending autonomic pathways, generating NO-mediated smooth muscle relaxation and penile tumescence independent of the PDE5/cGMP pathway — explaining why it works in some men with PDE5 inhibitor-refractory ED.
Is there evidence of melanoma risk from MT-II use?
Direct epidemiological evidence linking MT-II to melanoma is lacking due to absence of large controlled human studies. However, MC1R is a known melanoma susceptibility gene, and prolonged agonism theoretically promotes melanocyte proliferation. Case reports of rapidly changing nevi in MT-II users exist in the literature (e.g., Langan EA et al., 2009, Br J Dermatol). Individuals with high nevus counts or MC1R loss-of-function variants (red hair phenotype) are likely at higher relative risk.
How does MT-II compare pharmacologically to PT-141 (Bremelanotide)?
PT-141 is the metabolite of MT-II formed by cleavage of the C-terminal amide. It retains MC3R and MC4R agonism but has markedly reduced MC1R affinity, explaining why PT-141 produces sexual effects without significant tanning. MT-II is less receptor-selective, hence its broader side effect profile and multi-system activity.
What is the evidence level?
This compound is classified as Limited human data. Some human data exists but trials are small, short-term, or not yet replicated.
Research
Research & sources
Current evidence for Melanotan II is rated as Limited human data. Limited human data is available.
- 1. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization (2006) — Peptides 27(4):921-30. DOI: 10.1016/j.peptides.2005.01.029
- 2. Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study (1998) — Journal of Urology 160(2):389-93. DOI: 10.1016/S0022-5347(01)62898-9
- 3. Langan EA, et al. Melanotropic peptide use and possible association with melanoma (2009) — British Journal of Dermatology 161(5):1187-8. DOI: 10.1111/j.1365-2133.2009.09336.x
- 4. Raposinho PD, et al. Melanocortin-4 receptor agonism causes weight loss via a mechanism involving mechanisms in the hypothalamic-pituitary axis (2003) — Neuroendocrinology 78(1):1-9
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