Melanotropic peptides: what exactly is meant by "melanotan"?

Sir, We read with interest the letter from Thestrup-Pedersen & Søndergaard (1) reporting the augmentation of len-tiges and naevi in a young male patient who had been self-injecting with " melanotan ". As in a case we initially reported (2), a clinically suspicious naevus was excised, with histology revealing a benign naevus, with no evidence of malignant transformation. The patient was also noted to be particularly tanned. This report is in keeping with previous case reports, in which the use of " melano-tan " has been associated with both changes in the clinical presentation of pre-existing, and the development of new, naevi (2–4). Thus, dermatologists need to be aware of the increasing self-medication by the public of melanotropic peptides, and the presence of an unexpected tan may alert the physician to their use (5). Clinically suspicious naevi must, of course, be excised. Regarding the recent case report (1), we respectfully draw attention to the fact that " melanotan " is not synonymous with " melatonin. " The latter, a pineal gland hormone synthesized from tryptophan, plays a major role in the regulation of circadian rhythms, and is some times utilized for its anti-jet-lag effects (6). Whilst there is evidence that the skin itself may be an important source of melatonin (6), its effects in terms of pigmentation appear to be an inhibition of melanogenesis and melano-cyte proliferation, at least in rodent melanoma cell lines (7). Perhaps inadvertently, the authors have highlighted the confusing complexity of nomenclature in the field of melanotropic peptides. The tridecapeptide hormone α-melanocyte stimulating hormone (α-MSH) is known to play a key role in human pigmentation. Produced locally by keratinocytes, and acting via the melanocor-tin-1 receptor (MC1R) on melanocytes, it stimulates melanogenic enzymes, including tyrosinase. This results in increased eumelanin production, and consequently increased pigmentation (5). In the early 1980s, the synthetic melanocortin, 4-Norleucine, 7-D-phenylalanine-α-MSH ([Nle4-D-Phe7]-α-MSH), was identified and found to have prolonged activity at the MC1R, with subcutaneous administration in humans resulting in increased cutaneous pigmentation (5). [Nle4-D-Phe7]-α-MSH has previously been reported in the literature as melanotan or melanotan-1 (8). Melanotan-2 is a shorter cyclic variant, which increases pigmentation at lower cumulative doses than [Nle4-D-Phe7]-α-MSH, but has the side-effect of penile erections, possibly via an effect on the MC3R in the central nervous system (5). Furthermore, α-MSH analogues in development are also at risk of falling under the popular term " melanotan " , thus adding …