Melanotan

Melanotan is a synthetic analogue of alpha-melanocyte stimulating hormone (α-MSH), a hormone belonging to the melanocortin group of peptide hormones, which have different bodily functions. α-MSH binds to different melanocortin receptors to produce different effects, including the following:

Increases melanin production by binding to the melanocortin 1 receptor (MC1R), stimulating the production of different enzymes, including tyrosinase. It also appears to stimulate melanocyte proliferation. Produces erections and increases libido by binding to MC3R in the central nervous system. Unlike sildenafil, a phosphodiesterase-5 inhibitor that produces erections using a peripheral effect, it does not require sexual stimulation, and its effect is longer-lasting. Decreased appetite. The anorexigenic effect is caused by the hormone binding centrally to the MC4R and peripherally to the MC2R; it also appears that it may affect lipolysis by binding to the MC5R. Immunomodulating effects. It appears to diminish the body’s inflammatory and immune responses. Vasopressors affect the cardiovascular system and increase blood pressure. Changes in behaviour. The effects in this regard are highly variable and may affect learning, attention, and motor coordination, in addition to modifying sexual and eating behaviours.

Melanotan-1 and Melanotan-2

There are 2 synthetic Melanotan molecules: Melanotan-1 and Melanotan-2.

Melanotan-1 ([Nle4-D-Phe7]-α-MSH) is a 13 amino acid linear peptide in which the fourth amino acid, methionine, is replaced with norleucine and the seventh amino acid, L-phenylalanine, is replaced with D-phenylalanine. This molecule is more resistant to breakdown than its natural analogue, which means that the stimulus received by its receptor (principally MC1R) is more potent.

Melanotan-2 (Ac-Nle-[Asp-His-D-Phe-Arg-Trp-Lys]-α-MSH-NH2) is a shorter variant with a lactam ring. Like melanotan I, this analog is more potent than natural α-MSH but has more side effects because it is less receptor-specific. In addition to stimulating increased melanin production, this molecule decreases appetite and increases libido.

The Melanotan-1 and Melanotan-2 molecules were originally developed to investigate their effects on melanin production to increase the natural photoprotective effect provided by this hormone. Both molecules proved to effectively increase melanin when injected, and the type of melanin produced was eumelanin (which provides greater protection to cells than pheomelanin). However, as a side effect, Melanotan II also produced penile erection. This led to research on Melanotan II as a photoprotector being abandoned, and attention was focused on melanotan I, which is more selective of melanin production. Nevertheless, melanotan II did not disappear; it moved to another area of research: erectile dysfunction. Thus, we find that these two molecules have advanced in different areas:

Melanotan-1 (SCENESSE, Clinuvel Pharmaceuticals Ltd) is being studied in phase 2 and phase 3 clinical trials as a photoprotective drug for protection against nonmelanoma skin cancer and in other photoinduced skin diseases, such as erythropoietic protoporphyria, solar dermatitis, and polymorphic light eruption. The results of these trials appear to be promising.

Melanotan-2 was replaced by a nasally administered molecule (PT-141, Palatin Technologies), which was studied in erectile dysfunction. It was found to produce erections using a central mechanism, unlike sildenafil, and to produce a lasting erection independent of sexual stimulation in 80% of patients who did not respond to sildenafil. Although promising, the molecule was never brought to market due to several patients presenting with high blood pressure. The same company is currently studying its use in hemorrhagic shock.