Effects of a potent synthetic melanotropin, Nle<sup>4</sup>-D-Phe<sup>7</sup>-α-MSH (Melanotan-I) on tanning: a dose-ranging study

Levine, Norman; Dorr, Robert T.; Ertl, Gregory; Brooks, Carla; Alberts, David S.

doi:10.3109/09546639909056014

Cited by 15 publications

(17 citation statements)

References 14 publications

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“…The daily dose was 0.16 mg/kg, twice that used in the previous placebo-controlled randomized study (3). This dose was established to produce maximal drug-induced tanning with minimal toxicity in a Phase I dose-escalation study (24). Subjects were surveyed for side effects, if any, at the time of each injection, at daily follow-up visits and one week (day 21) and four weeks after dosing ended.…”

Section: Clinical Trial Methodsmentioning

confidence: 99%

Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶

Dorr¹,

Dvořáková²,

Brooks³

et al. 2000

Photochem Photobiol

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Seven normal volunteers (six males and one female) with tanning skin types III or IV (Fitzpatrick scale) were given 10 daily subcutaneous injections of a superpotent synthetic analog of alpha-melanocyte stimulating hormone (alpha-MSH) over two weeks. This agent, [Nle4-D-Phe7]alpha-MSH, also called Melanotan-I (MT-I), was administered at a dose of 0.16 mg/kg/day (Monday-Friday), over a two week period. Tanning was measured serially using computerized light reflectance. This regimen induced tanning at 3 of 8 anatomic sites including the face, neck and forearm by comparison of baseline to (1) the end of the daily dosing period, (day 14), and (2) one week later, (day 21). Shave biopsies of the forearm taken at baseline and day 21 were analyzed by high performance liquid chromatography for eumelanin content which was measured as the permanganate oxidation product, pyrrole-2,3,5-tricarboxylic acid or PTCA. Pheomelanin content was measured as the hydroiodic acid digestion product, aminohydroxyphenylalanine (AHP). Eumelanin was also measured in the forehead skin samples of three subjects. The HPLC results show that mean (+/- SD) baseline eumelanin (PTCA) levels in forehead skin (n = 3) averaged 1.38 (+/- 0.87) ng/mg of wet skin tissue weight. Higher mean baseline levels of PTCA were detected in forearm skin (2.06 +/- 0.28 ng/mg wet weight, n = 7). One week after MT-I treatments ended, there was a mean (SD) 49% (+/- 17.6%) increase in forehead skin PTCA levels compared to baseline (P = 0.019, n = 3, by paired sample T-test). The mean (SD) increase in forearm skin PTCA levels was 98% (+/- 25.4%) over the same period (P = 0.003). In contrast, forearm pheomelanin expression following MT-I treatment did not significantly change from baseline. Overall, the MT-I regimen increased the eumelanin: pheomelanin ratio in forearm skin from 51:1 at baseline to 86:1 following MT-I (P = 0.054 by paired sample T-test). These results show that the tanning induced by MT-I in the face and forearm is associated with a significant increase in the eumelanin content of the human skin.

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Section: Clinical Trial Methodsmentioning

confidence: 99%

Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶

Dorr¹,

Dvořáková²,

Brooks³

et al. 2000

Photochem Photobiol

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“…The recent developments in the optimisation of Fourier transform infrared (FTIR) spectroscopy indicate the increasing potential of this technique to highlight compositional differences, in particular a unique chemical profile in the outer segments of pigmented retina compared to other retinal layers, and this profile was altered in albino animals (Levine et al 1999). Further developments using mid-infrared beamline IRENI (InfraRed ENvironmental Imaging) enabled study of changes in saturated and unsaturated fatty acid ester content in the neuronal layers of the retina.…”

Section: Analysis/detection Of the Melanin Typesmentioning

confidence: 99%

The Pigment in Alkaptonuria Relationship to Melanin and Other Coloured Substances: A Review of Metabolism, Composition and Chemical Analysis

et al. 2015

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The pigments found in plants, animals and humic substances are well described and classified. In humans considerable progress has been made with the main pigment melanin in defining its biochemistry, the different types and function. However, analytical techniques to show these differences in vivo are still not readily available. NMR and IR spectroscopy are relatively insensitive and reveal only major structural differences. Techniques utilising MS are useful in determining elemental content but require further studies to optimise conditions for accurate mass analysis. How the components may be structurally organised seems to be the most problematic with scanning TEM and the improved FTIR of use in this respect. As regards understanding the nature of the pigment related to HGA seen in patients with Alkaptonuria (AKU), it is still thought of as a melaninlike pigment simply because of its colour and likewise thought to be a polymer of undetermined size. It is important that detailed analysis be carried out to define more accurately this pigment. However, observations suggest it to be the same as the HGA-derived pigment, pyomelanin, produced by bacteria and containing both quinone and phenolic groups. The interesting developments in alkaptonuria will be to understand how such a polymer can cause such profound collagen and connective tissue damage and how best to reverse this process.

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“…Although all subjects tanned during the study, and there was no improved tanning beyond that obtained at the 0.16 mg/kg dose, setting it as the optimal dosage. Besides, the 0.16 mg/kg dose did not show toxicities over grade 2 grading based on World Health Organization (WHO) criteria [63]. Another study using this 0.16 mg/kg dose in skin type III-IV volunteers (six males and one female) containing 10 daily subcutaneous injections over two weeks, confirmed increased tanning by particularly eumelanin expression, while overall there was no increase in pheomelanin expression (except in one subject who experienced a substantial increase in eumelanin and pheomelanin) [50].…”

Section: Pharmacodynamics Pharmacokinetics and Metabolismmentioning

confidence: 93%

Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria

Wensink

Wagenmakers

Langendonk

2021

Expert Review of Clinical Pharmacology

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Introduction: In erythropoietic protoporphyria (EPP), an inherited disorder of heme biosynthesis, accumulation of protoporphyrin IX results in acute phototoxicity. EPP patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life. Afamelanotide is the first effective approved medical treatment for EPP, acting on melanocortin-1 receptors. This article aims to review afamelanotide. Areas covered: This review summarizes the chemical properties, pharmacokinetics, safety, preclinical and clinical data on afamelanotide in EPP, and post-marketing surveillance. PubMed search, manufacturers' websites, and relevant articles used for approval by authorities were used for the literature search. Expert opinion: Afamelanotide is an α-melanocyte-stimulating hormone analog. It can activate eumelanogenesis without exposure to UV radiation. Clinical studies in EPP showed that afamelanotide treatment significantly increased exposure to sunlight and QoL. In our clinical experience afamelanotide treatment is much more effective in clinical practice than demonstrated in clinical trials and should be made available for all EPP patients meeting inclusion criteria. The 60-day interval period was not based on effectiveness studies, and therefore for some of the patients the maximum of four implants per year with the 60-day interval is insufficient. Afamelanotide is well tolerated; common adverse events were headache, fatigue, and nausea.

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Effects of a potent synthetic melanotropin, Nle⁴-D-Phe⁷-α-MSH (Melanotan-I) on tanning: a dose-ranging study

Cited by 15 publications

References 14 publications

Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶

Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶

The Pigment in Alkaptonuria Relationship to Melanin and Other Coloured Substances: A Review of Metabolism, Composition and Chemical Analysis

Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria

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Effects of a potent synthetic melanotropin, Nle4-D-Phe7-α-MSH (Melanotan-I) on tanning: a dose-ranging study

Cited by 15 publications

References 14 publications

Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶

Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶

The Pigment in Alkaptonuria Relationship to Melanin and Other Coloured Substances: A Review of Metabolism, Composition and Chemical Analysis

Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria

Contact Info

Product

Resources

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Effects of a potent synthetic melanotropin, Nle⁴-D-Phe⁷-α-MSH (Melanotan-I) on tanning: a dose-ranging study