Melanotan I Compound Overview
Class of Compound: Peptide
Mechanism of Action: Melanotan I is an agonist of melanocortin receptors 1, 3, 4, and 5, binding primarily to melanocortin receptor 1 to trigger melanin production.
Notable Studies: Increased eumelanin expression and Skin diseases tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-alpha-MSH in humans. Effects of a superpotent melanotropic radiation on tanning of the skin in human volunteers. A phase II, randomised, open label pilot study to evaluate the efficacy and safety of two dosage regimens of subcutaneous bioresorbable afamelanotide implants in patients with mild to moderate acne vulgaris.
Research Applications: Skin tanning, Skin diseases, Erectile dysfunction.
Risks: Limited official approval, Mild, Administration-related symptoms, Administration-related symptoms.
What is Melanotan I?
Melanotan is a synthetic analogue of alpha-melanocyte-stimulating hormone, or a-M5H for short. a- M51-1 is one of a number of melanocortin peptide hormones in the body. Melanotan is typically injected or administered as an implant and binds to melanocortin receptors 1, 3, 4, and 5.
There are two types of melanotan molecules: melanotan I and melanotan II. They have both been linked to increased melanin production and increased tanning of the skin.
While there is strong research interest in both melanotan molecules, this review will focus on melanotan I.
What Does Melanotan I Do?
Melanotan I (Nle-D-Phe]-a-MSH) is a synthetic peptide that has a linear formation. It is 13 amino acids in length and has the same structure as a-MSH save for two key differences. First, the fourth amino acid in melanotan I is norleucine; second, the seventh amino acid is D-phenylalanine.
In the body, melanotan I primarily binds with the MC1R receptor and is more potent and resistant to breakdown than a-MSH. Studies have shown that MT-1 significantly enhances tanning and reduces sunburn.
Melanotan I should not be confused with melanotan II (Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys]- a-MSH- NH2). MT-2 is less receptor-specific than melanotan I and has been linked to more side effects. Studies have shown that melanotan II increases libido and decreases appetite to a greater extent than MT-1.
Melanotan I Benefits I Clinical Trials
A number of clinical trials have evaluated the safety and efficacy of melanotan I, from which the following benefits can be drawn.
Increased melanin production and rate of tanning
Melanotan I binds to the melanocortin 1 receptor (MC1R), thereby increasing melanin production. This has the secondary effect of increasing levels of the enzyme tyrosinase and melanocyte. Studies have found that MT-1 can increase the rate of tanning and reduce the number of sunburnt cells in test subjects.
Three phase I clinical trials conducted by dermatology clinics at the Arizona Health Sciences Center have investigated two dose levels of melanotan I combined with small doses of UV-B to the neck or buttock, or full sunlight to half of the back. In these trials, test subjects receiving melanotan I had 47% fewer sunburn cells on their neck and “significantly enhanced tanning° on their back compared with the control group.
Improved mood and outlook
Results from several phase II clinical trials sponsored by Clinuvel Pharmaceuticals have shown that melanotan I offers psychological benefits including improved mood and outlook in patients who had received photodynamic therapy (PDT), a treatment that uses light and photosensitization to kill cancer cells.
A 2008 phase II multicentre, double-blind, placebo controlled pilot study aimed to evaluate whether melanotan I implants (referred to in the study as afarnelanotide implants) could reduce the period of phototoxicity experienced by patients who have undergone photodynamic therapy with porfimer sodium.
Based on findings from 16 patients who received study treatment (9 MT-1, 7 placebo), patients treated with melanotan I experienced positive changes in their mood and mental health compared to placebo. A secondary effect was reduced pain, which could have resulted in these changes.
A second follow-up trial was started in the same year and aimed to evaluate the safety of subcutaneous bioresorbable implants of CUV1647 (melanotan I). Results for this trial are not available.
Potential acne treatment
Melanotan I has been investigated as a potential treatment for acne vulgaris. In 2011 a phase II randomized study was conducted in Germany to evaluate the efficacy and safety of two dosage regimens of subcutaneous bioresorbable afamelanotide implants in patients with mild to moderate acne vulgaris.
The study found that test subjects treated with melanotan I (either three injections at 3-week intervals, or two injections at 4-week intervals) experienced a decline in the number of inflammatory acne lesions on their faces. Researchers also found that quality of life as measured by DLQI improved in all patients from day 0 to day 56 and patients treated with melanotan I were able to spend up to seven times longer in direct sunlight without experiencing pain.
Another phase II randomized pilot study that aimed to evaluate the same melanotan I implant and narrow-band ultraviolet B (NB-UVB) light was also published in 2011. Results for this trial are not available.
Potential treatment for xeroderma pigmentosum
Melanotan I has been investigated as a treatment for xeroderma pigmentosum (XP), an inherited condition characterized by extreme sensitivity to ultraviolet (UV) light. In 2019, a proof of concept, phase Ila open label study in Germany aimed to evaluate the safety and efficacy of melanotan I implants in patients with XP. Another phase Ila study was started in 2021 and is currently ongoing.
Potential treatment for polymorphic light eruption
A 2010 phase III, randomized, double blind, placebo controlled, parallel group study was undertaken in Germany, the Netherlands, and Belgium to evaluate the safety and efficacy of subcutaneous implants of melanotan I (16 mg) in patients suffering from polymorphic light eruption (PLE), a condition characterized by a rash following exposure to sunlight.
Researchers found that melanotan I could reduce the severity of PLE related pruritus when administered as 16 mg implants over a period of 4 months.
Potential treatment for erythropoietic protoporphyria
A 2011 phase III study in Europe aimed to confirm the safety and efficacy of subcutaneous bioresorbable melanotan I implants in patients with Erythropoietic Protoporphyria (EPP). The study aimed to determine whether 16 mg melanotan I implants could improve the quality of life of EPP patients. Researchers found that test subjects in the melanotan I group experienced less pain and a higher quality of life compared with those in the placebo group.
Melanotan Side Effects
Based on findings from clinical studies, melanotan I appears to have a favorable safety profile. There have been no reported safety concerns, no significant drug-related adverse events, no deaths, and no adverse events leading to discontinuation of a study.
Based on the research, the only side effects linked to melanotan I are:
- Nausea
- Transient facial flushing
- A case of mild and short-term fatigue in one patient
Is Melanotan I Safe?
Melanotan I is a research chemical and has no safe or recommended dosage. While data from clinical studies suggests that this peptide has a positive safety profile, there are several cases reported in the literature to show why experimentation with this peptide is limited to in vitro experimentation only.
Cousin et al. described a case of eruptive melanocytic naevi following melanotan I injection, Evans-Brown et al. described the potentially harmful effects of melanotan I and melanotan II, According to Langan et al. melanotan I use has been linked to changes in moles, Dreyer et al. described a case of melanotan-induced priapism.
In summary, administration of melanotan I is restricted to clinicians and researchers.
Melanotan I Dosage Calculator
For tanning of the skin, research suggests a melanotan I dosage range of 0.2 5mg to 2mg a day. It is advisable to start at the lowest possible dose, before increasing to achieve the desired outcome.
Researchers interested in studying the potential of melanotan Ito treat a variety of skin disorders may consult the above-cited clinical trials to gain a fuller understanding of how this peptide has been dosed.
Melanotan 1 dosages ranging from 0.08mg/kg to 0.16mg/kg per day were implemented in phase I studies in Europe. The phase II and III European studies involved 16mg melanotan I implants for a treatment period of up to tour months.