Risks of unregulated use of alpha‐melanocyte‐stimulating hormone analogues: a review

Abstract

Recently, the unregulated use of untested synthetic alpha-melanocyte-stimulating hormone (α-MSH) analogues, commonly known as melanotan I and II, appears to have increased. These analogues are primarily used for their tan-stimulating effects. Dermatologists see many patients in their clinic who tan. This review provides an overview of the risks of the unregulated use of these substances. Other topics discussed here include the history and safety of afamelanotide, which is the only α-MSH analogue that is approved for use in a limited number of medical indications. Although afamelanotide has been thoroughly tested and deemed safe, illegal melanotans are likely risky for several reasons. There are questions regarding the preparation, administration, and dosage of these substances. In addition to these general risks, increasing numbers of case reports indicate that the unregulated use of both melanotan I and II is associated with cutaneous complications, particularly melanocytic changes in existing moles and newly emerging (dysplastic) nevi. Four case reports have described melanomas emerging from existing moles either during or shortly after the use of melanotan. Although conclusive evidence linking these phenomena is lacking, publications have stressed the importance of awareness that melanotan is a part of a 'tanning culture' in certain subpopulations. Multiple national health organizations have issued safety warnings regarding the use of melanotan I and II.

Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition

“…Moreover, MTII administration elicited the anti-melanoma function through the multiple cellular mechanism including proliferation inhibition, apoptosis induction, and neovascularization blockage. Therefore, our study does not endorse the view that the sun-tanning agent MTII increases the risk of melanoma [30]. Although the detailed mechanism on PTEN stability and post-translational modification (such phosphorylation, ubiquitination etc.)…”

“…Interestingly, MTII has been proposed to hold therapeutic potential for erectile dysfunction and female arousal and orgasmic disorders [29]. However, the safety and oncogenic potential of MTII remain equivocal [30]. Therefore, the present study evaluates the effects of MTII on the oncogenic behaviors of the B16-F10 melanoma cell in vitro.…”

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

“…MC1R is the target for, e.g., superpotent [Nle 4 ,D-Phe 7 ]-α-MSH (NDP-MSH) (melanotan I) [62,63] or tetrapeptides and tripeptides containing the core sequence [64,65] when hormoneinduced tanning of the skin is envisaged, be it for cosmetic reasons or to protect the skin by an increased tan from the risk of melanoma formation. However, uncontrolled and prolonged use of potent MSH agonist peptides is risky on its own because of potential induction of malignant moles by the hormones [66]. In fact, a recent study demonstrated that chronic expression of agouti signaling peptide (ASIP), a physiological antagonist/inverse agonist of MC1R [67], in the tumor microenvironment of experimental cutaneous or metastatic lung melanoma provided a survival advantage to melanomabearing mice [68].…”

LC‐HRMS characterization of the skin pigmentation and sexual enhancers melanotan II and bremelanotide sold on the black market of performance and image enhancing drugs

“…As users often self-estimate the dosage, their abuse can lead to acute adverse reactions, like facial flushing, nausea and vomiting, as well as cutaneous diseases, such as nonhomogeneous skin pigmentation, haematomas, growth/darkening in existing nevi or newly emerging nevi, which carry a high risk of developing into melanoma. 8,9 Melanotan II use also resulted in systemic toxicity including apparent sympathomimetic symptoms, rhabdomyolysis and renal dysfunction. 10 Techniques routinely used in laboratories for the identification of unknown compounds, such as gas chromatography-mass spectrometry (GC-MS), are not suitable to analyze peptides since they cannot be vaporized and detected due to their high molecular weights.…”