Melanotan I

Overview

Melanotan I (afamelanotide) is a linear 13-amino acid analogue of α-MSH with a single substitution (Nle4) that increases its potency and resistance to enzymatic degradation. Unlike Melanotan II, it is more selective for MC1R over MC3R and MC4R, which reduces the sexual side effects and nausea seen with MT-II. This selectivity profile made it a more suitable candidate for pharmaceutical development.

A long-acting implant formulation (Scenesse/Clinuvel) was approved by the EMA in 2014 and by the FDA in 2019 for preventing phototoxic reactions in patients with erythropoietic protoporphyria (EPP), a rare metabolic disorder causing extreme light sensitivity. Research continues into its photoprotective properties in other photosensitivity disorders, vitiligo, and non-EPP dermatological applications.

Mechanism of Action

Afamelanotide binds preferentially to MC1R on epidermal melanocytes, stimulating adenylyl cyclase and the cAMP/PKA pathway to increase tyrosinase expression and activity. This produces eumelanin (brown-black pigment) in preference to phaeomelanin (red-yellow), as eumelanin provides superior UV photoprotection. The increase in melanin density in the epidermis reduces UV-induced DNA damage.

Research Areas

• ●Erythropoietic protoporphyria photoprotection
• ●Selective MC1R pharmacology
• ●UV photoprotection and melanogenesis
• ●Vitiligo repigmentation research
• ●Solar urticaria and photosensitivity disorders
• ●Melanoma prevention research

Storage & Handling

For Research Use Only. This information is provided for educational and research purposes. Melanotan I is not approved for human consumption, veterinary use, or clinical application. All research must be conducted in accordance with applicable laws and institutional guidelines.