Melanotan 1

In 1980 a research group described in PNAS an alpha-MSH analogue in which two amino acids had been swapped: norleucine in position 4, D-phenylalanine in position 7. The result resisted serum enzymes and, in an adenylate cyclase assay, proved 26 times as active as the natural hormone. This 13-amino-acid molecule is known today as melanotan 1 or afamelanotide; the two substitutions extend its half-life compared with the original.

The mechanism is narrowly defined: the peptide switches on MC1R, the melanocortin-1 receptor of the melanocytes. Tyrosinase activity rises there and the cells produce more eumelanin. In studies, pigmentation increased with dose and over time. Unlike melanotan 2, which engages several receptor subtypes, melanotan 1 largely leaves MC3R and MC4R alone. For questions limited to the pigment pathway it is therefore the cleaner tool.

Findings in humans:

• Three phase 1 studies paired the peptide with either UV-B lamps or natural sunlight. Tanning was stronger and lasted at least three weeks longer than in the control group.
• In dermatology it was tested as an implant releasing over weeks in erythropoietic protoporphyria; a study on this appeared in the New England Journal of Medicine in 2015.
• Pharmacokinetically it is fully available after subcutaneous dosing, whereas the oral and transdermal routes left no measurable trace in plasma.

The peptide's own half-life is short, around 30 minutes, which explains the depot forms used in clinical research.

Here you get melanotan 1 strictly as a research compound; this text is context, not a guide to use.

Thanks to its clinical development the documentation on melanotan 1 is comparatively solid, and its MC1R selectivity gives it the milder profile of the two melanotans. Several things were observed nonetheless:

• Shortly after dosing, nausea and a queasy feeling are reported fairly often.
• Facial flushing with transient warmth is described in the studies.
• Pigment changes: moles, freckles and already pigmented areas can darken. Changes in moles are treated as a warning sign in the literature.
• The injection site itself often reacts with redness or tenderness.
• There is little robust data on longer-term use outside clinical trials; the picture rests on dermatological studies and anecdotal reports.

This summary is no substitute for medical advice.

• 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity - the first description from 1980 with the 26-fold potency value in the adenylate cyclase assay.
• Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers - three phase 1 studies with UV light: stronger and longer-lasting tanning, with nausea and flushing as side effects.
• Afamelanotide for the treatment of erythropoietic protoporphyria - 2015 clinical study of the implant form in protoporphyria.