Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers

Abstract

Three phase 1 clinical trials of a superpotent melanotropic peptide, melanotan-1 (MT-1, or [Nle 4 -D-Phe 7 ]␣-melanocyte-stimulating hormone) were performed to demonstrate safety for MT-1 therapy combined with UV-B light or sunlight. Design: Open-label studies at 2 dose levels of MT-1 combined with small doses of UV-B to the neck or buttock or full sunlight to half of the back.

[Nle4-D-Phe7]-α-Melanocyte-Stimulating Hormone Significantly Increased Pigmentation and Decreased UV Damage in Fair-Skinned Caucasian Volunteers

“…We used both chromaticity and a new method to monitor skin darkening. The reduction of 1-2 on the L* chromaticity scale in this study is similar but slightly lower than previous reports of skin tanning using [Nle 4 -D-Phe 7 ]-a-MSH at this dosage (Levine et al, 1991;Dorr et al, 2004). In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units.…”

“…The estimation of skin cell damage using 3 Â MED of UVR exposure is well accepted (Dorr et al, 2004). Although two different solar simulators were used in this study, the MED estimations at both study centers were remarkably consistent with no statistical difference between the two sites.…”

“…In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units. It is noteworthy that Dorr et al (2004) obtained a mean 10-unit decrease in luminance when [Nle 4 -D-Phe 7 ]-a-MSH administration was combined with sunlight exposure. Our results indicate that the estimation of MD by the method of Dwyer et al (1998) appears to provide a good estimation of melanin changes as shown by the actual biopsy measurements.…”

“…Extended duration of melanization after the end of treatment is very likely because of the residence time that melanin will remain in the keratinocytes until the normal process of desquamation removes them; there may also be an extended duration of increased melanin production within the melanocytes. Also in a recent paper (Dorr et al, 2004), it was shown that [Nle 4 -D-Phe 7 ]-a-MSH in combination with a minimal amount of sun exposure extended the skin tanning effect from about 4 weeks with [Nle 4 -D-Phe 7 ]-a-MSH alone to at least 11 weeks with 30-minute sun exposure a day for 3-5 days.…”

[Nle4-D-Phe7]-α-Melanocyte-Stimulating Hormone Significantly Increased Pigmentation and Decreased UV Damage in Fair-Skinned Caucasian Volunteers

“…We used both chromaticity and a new method to monitor skin darkening. The reduction of 1-2 on the L* chromaticity scale in this study is similar but slightly lower than previous reports of skin tanning using [Nle 4 -D-Phe 7 ]-a-MSH at this dosage (Levine et al, 1991;Dorr et al, 2004). In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units.…”

“…The estimation of skin cell damage using 3 Â MED of UVR exposure is well accepted (Dorr et al, 2004). Although two different solar simulators were used in this study, the MED estimations at both study centers were remarkably consistent with no statistical difference between the two sites.…”

“…In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units. It is noteworthy that Dorr et al (2004) obtained a mean 10-unit decrease in luminance when [Nle 4 -D-Phe 7 ]-a-MSH administration was combined with sunlight exposure. Our results indicate that the estimation of MD by the method of Dwyer et al (1998) appears to provide a good estimation of melanin changes as shown by the actual biopsy measurements.…”

“…Extended duration of melanization after the end of treatment is very likely because of the residence time that melanin will remain in the keratinocytes until the normal process of desquamation removes them; there may also be an extended duration of increased melanin production within the melanocytes. Also in a recent paper (Dorr et al, 2004), it was shown that [Nle 4 -D-Phe 7 ]-a-MSH in combination with a minimal amount of sun exposure extended the skin tanning effect from about 4 weeks with [Nle 4 -D-Phe 7 ]-a-MSH alone to at least 11 weeks with 30-minute sun exposure a day for 3-5 days.…”

Investigation of safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of a long‐acting α‐MSH analog in healthy overweight and obese subjects

“…It is known that exposure to α‐MSH analogs leads to up‐regulation of MC1 receptors in the skin and in congenital nevi expression of MC1 receptors are increased; this, along with exposure to UV radiation (which indirectly stimulates α‐MSH secretion), leads to increased expression of MC1 receptors . Furthermore, a synergistic effect on tanning of melanotan‐I and UV‐B light was reported by Dorr et al Although MC4‐NN2‐0453 is an analog with very high receptor specificity for the MC4R versus the MC1R, the high‐exposure level and the eventual increase in MC1R expression could explain the increase in number and pigmentation of nevi both in sun‐exposed and acral area as well as the hyperpigmentation induced by MC4‐NN2‐0435 in this trial. Acral nevi have been shown to be associated with ethnicity, pigmentation, age, and cutaneous melanoma risk factors and are not uncommon phenomena …”

[Nle4-D-Phe7]-α-Melanocyte-Stimulating Hormone Significantly Increased Pigmentation and Decreased UV Damage in Fair-Skinned Caucasian Volunteers

“…We used both chromaticity and a new method to monitor skin darkening. The reduction of 1-2 on the L* chromaticity scale in this study is similar but slightly lower than previous reports of skin tanning using [Nle 4 -D-Phe 7 ]-a-MSH at this dosage (Levine et al, 1991;Dorr et al, 2004). In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units.…”

“…The estimation of skin cell damage using 3 Â MED of UVR exposure is well accepted (Dorr et al, 2004). Although two different solar simulators were used in this study, the MED estimations at both study centers were remarkably consistent with no statistical difference between the two sites.…”

“…In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units. It is noteworthy that Dorr et al (2004) obtained a mean 10-unit decrease in luminance when [Nle 4 -D-Phe 7 ]-a-MSH administration was combined with sunlight exposure. Our results indicate that the estimation of MD by the method of Dwyer et al (1998) appears to provide a good estimation of melanin changes as shown by the actual biopsy measurements.…”

“…Extended duration of melanization after the end of treatment is very likely because of the residence time that melanin will remain in the keratinocytes until the normal process of desquamation removes them; there may also be an extended duration of increased melanin production within the melanocytes. Also in a recent paper (Dorr et al, 2004), it was shown that [Nle 4 -D-Phe 7 ]-a-MSH in combination with a minimal amount of sun exposure extended the skin tanning effect from about 4 weeks with [Nle 4 -D-Phe 7 ]-a-MSH alone to at least 11 weeks with 30-minute sun exposure a day for 3-5 days.…”

Investigation of safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of a long‐acting α‐MSH analog in healthy overweight and obese subjects

“…It is known that exposure to α‐MSH analogs leads to up‐regulation of MC1 receptors in the skin and in congenital nevi expression of MC1 receptors are increased; this, along with exposure to UV radiation (which indirectly stimulates α‐MSH secretion), leads to increased expression of MC1 receptors . Furthermore, a synergistic effect on tanning of melanotan‐I and UV‐B light was reported by Dorr et al Although MC4‐NN2‐0453 is an analog with very high receptor specificity for the MC4R versus the MC1R, the high‐exposure level and the eventual increase in MC1R expression could explain the increase in number and pigmentation of nevi both in sun‐exposed and acral area as well as the hyperpigmentation induced by MC4‐NN2‐0435 in this trial. Acral nevi have been shown to be associated with ethnicity, pigmentation, age, and cutaneous melanoma risk factors and are not uncommon phenomena …”

[Nle4-D-Phe7]-α-Melanocyte-Stimulating Hormone Significantly Increased Pigmentation and Decreased UV Damage in Fair-Skinned Caucasian Volunteers

“…We used both chromaticity and a new method to monitor skin darkening. The reduction of 1-2 on the L* chromaticity scale in this study is similar but slightly lower than previous reports of skin tanning using [Nle 4 -D-Phe 7 ]-a-MSH at this dosage (Levine et al, 1991;Dorr et al, 2004). In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units.…”

“…The estimation of skin cell damage using 3 Â MED of UVR exposure is well accepted (Dorr et al, 2004). Although two different solar simulators were used in this study, the MED estimations at both study centers were remarkably consistent with no statistical difference between the two sites.…”

“…In this study, participants were encouraged to avoid the sun where possible and to use sunblock when exposed, and this may account for the relatively small change in luminance units. It is noteworthy that Dorr et al (2004) obtained a mean 10-unit decrease in luminance when [Nle 4 -D-Phe 7 ]-a-MSH administration was combined with sunlight exposure. Our results indicate that the estimation of MD by the method of Dwyer et al (1998) appears to provide a good estimation of melanin changes as shown by the actual biopsy measurements.…”

“…Extended duration of melanization after the end of treatment is very likely because of the residence time that melanin will remain in the keratinocytes until the normal process of desquamation removes them; there may also be an extended duration of increased melanin production within the melanocytes. Also in a recent paper (Dorr et al, 2004), it was shown that [Nle 4 -D-Phe 7 ]-a-MSH in combination with a minimal amount of sun exposure extended the skin tanning effect from about 4 weeks with [Nle 4 -D-Phe 7 ]-a-MSH alone to at least 11 weeks with 30-minute sun exposure a day for 3-5 days.…”

Investigation of safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of a long‐acting α‐MSH analog in healthy overweight and obese subjects

“…It is known that exposure to α‐MSH analogs leads to up‐regulation of MC1 receptors in the skin and in congenital nevi expression of MC1 receptors are increased; this, along with exposure to UV radiation (which indirectly stimulates α‐MSH secretion), leads to increased expression of MC1 receptors . Furthermore, a synergistic effect on tanning of melanotan‐I and UV‐B light was reported by Dorr et al Although MC4‐NN2‐0453 is an analog with very high receptor specificity for the MC4R versus the MC1R, the high‐exposure level and the eventual increase in MC1R expression could explain the increase in number and pigmentation of nevi both in sun‐exposed and acral area as well as the hyperpigmentation induced by MC4‐NN2‐0435 in this trial. Acral nevi have been shown to be associated with ethnicity, pigmentation, age, and cutaneous melanoma risk factors and are not uncommon phenomena …”