Melanotan II

Melanotan II is a non-selective melanocortin receptor agonist. It binds to and activates MC1R, MC3R, MC4R, and MC5R with varying affinities. Each receptor mediates different effects:

MC1R (Pigmentation): MC1R is expressed on melanocytes in the skin. When activated, it triggers the cAMP-PKA signaling cascade, which upregulates tyrosinase, the enzyme that converts tyrosine to melanin. Specifically, MC1R activation shifts melanin production from pheomelanin (red-yellow pigment) toward eumelanin (brown-black pigment), producing the darkening effect. People with naturally red hair and fair skin (who produce more pheomelanin) often respond less to MT-II because their MC1R variants are less responsive.

MC4R (Sexual Function and Appetite): MC4R is expressed in the hypothalamus and is involved in both sexual arousal and appetite regulation. Activation of MC4R in the paraventricular nucleus stimulates pro-erectile signaling through oxytocin pathways. In the arcuate nucleus, MC4R activation suppresses appetite by inhibiting orexigenic (hunger-promoting) neurons. This dual role explains why MT-II simultaneously increases libido and decreases appetite.

MC3R (Energy Homeostasis): MC3R activation contributes to energy balance and fat metabolism, though its role is less prominent than MC4R in MT-II's effects.

MC5R (Exocrine Function): MC5R activation influences sebaceous gland secretion and may contribute to changes in skin oiliness some users report.

The combined activation of these receptors explains MT-II's multi-system effects. PT-141 was designed to be more selective for MC4R (sexual function) while reducing MC1R activation (tanning), creating a more targeted pharmacological profile.

Skin Tanning Without Excessive UV This is the headline use case. MT-II produces visible skin darkening in most users within the first 1-2 weeks. The tan develops from increased eumelanin production, not from UV-induced DNA damage. Some UV exposure accelerates and deepens the result, but many users achieve meaningful color change with minimal sun. For fair-skinned individuals, this can also provide partial photoprotection, as higher eumelanin levels absorb UV radiation and reduce DNA damage to keratinocytes.

Sexual Function Enhancement MT-II activates central arousal pathways via MC4R in the hypothalamus. Both men and women report increased libido, spontaneous arousal, and enhanced sexual satisfaction. In men, pro-erectile effects can be strong enough to cause erections without stimulation (particularly during the loading phase). This is not a peripheral blood-flow effect like PDE5 inhibitors (Viagra/Cialis). It works in the brain, increasing desire itself. For a more targeted sexual function peptide derived from MT-II, see PT-141.

Appetite Suppression MC4R activation in the hypothalamus suppresses hunger signaling. Users commonly report reduced appetite and smaller portion sizes without feeling deprived. The effect is moderate, not extreme like GLP-1 agonists such as Semaglutide, but it is a useful secondary benefit for those managing body composition.

Photoprotection Higher melanin levels in the skin provide a natural buffer against UV radiation. Some researchers have explored MT-II as a skin cancer prevention strategy, though this remains experimental. It does not replace sunscreen, but the increased pigmentation adds a layer of biological defense.

Mole Darkening (Cosmetic Consideration) Existing moles and freckles will darken alongside the rest of the skin. Some users consider this a downside, while others view it as neutral. It is important to monitor moles for changes in shape or irregularity during and after MT-II use, as altered pigmentation can make melanoma screening more difficult.

Common Side Effects (especially during loading phase): - Nausea (the most frequent side effect, often dose-dependent; starting low helps) - Facial flushing and warmth - Fatigue or drowsiness after injection - Spontaneous erections in men (can be inconvenient) - Darkening of existing moles and freckles - Mild injection site reactions

Less Common: - Headache - Dizziness - Abdominal cramping - Mild water retention - New moles or nevi appearing - Temporary changes in skin oiliness

Contraindications and Cautions: - Individuals with a personal or family history of melanoma should avoid MT-II. While the tanning effect is protective in theory, stimulating melanocyte activity in someone predisposed to melanoma is a concern that has not been adequately studied. - People with many atypical moles should exercise extreme caution and consult a dermatologist before use. - MT-II can complicate skin cancer screening by altering mole appearance. Establish a baseline mole check before starting. - Cardiovascular disease: MC4R activation can raise blood pressure transiently. Monitor if you have hypertension. - Pregnant or breastfeeding women should not use MT-II. - MT-II is not approved for human use in any jurisdiction. Quality control of research peptides varies significantly between suppliers.