Toxicologic studies of a superpotent alpha-melanotropin, [Nle4, D-Phe7]alpha-MSH.
Dorr. R T RT; Dawson. B V BV; al-Obeidi. F F; Hadley. M E ME; Levine. N N; Hruby. V J VJ
Key Findings
- No toxic effects on organs, blood counts, or weight gain at up to 2âŻmg/kg daily or weekly for 4â12âŻweeks in mice
- Slight increase in triglycerides and platelet counts after weekly dosing for 12âŻweeks
- No behavioral changes or cortisol/ACTHâlike endocrine effects observed
- Transdermal delivery through mouse skin was very low (0.002â0.05% of a 10â»âŽâŻM solution)
Practical Outcomes
- The peptide appears wellâtolerated in animals, so it may be safe for human trials, but start with low doses and monitor lipid and platelet levels during prolonged use. Because skin absorption is minimal, injectable routes are more practical than topical creams for achieving effective levels.
Summary
In mouse tests, a superâpotent melaninâboosting peptide (NDPâMSH) showed no major organ damage or hormone changes even at high doses for up to three months, though a small rise in blood fats and platelets was seen with weekly dosing. Skinâbased delivery worked, but only a tiny fraction of the drug actually passed through the skin, meaning injections are far more effective. The data suggest the compound is likely safe enough to move into early human trials, but users should watch blood lipids and platelets if they plan longâterm use.
Abstract
A toxicology study was performed in mice given a superpotent alpha melanocyte stimulating hormone (MSH) analog. This 13 amino acid derivative, [Nle4, D-Phe7]alpha-MSH or NDP-MSH, is a melanotropin which is very slowly biodegraded in vivo and is active at 1/1,000 the concentration of natural alpha-MSH. Mice were administered up to 2 mg/kg of the analog daily and weekly over 4 or 12 weeks by both topical application (in 90% DMSO) or by IP injections (in physiologic saline). At the end of this period, no toxic effects were observed in various organs, on hematologic indices, or on weight gain. A slight increase in triglyceride and platelet levels were noted in mice given the analog weekly for 12 weeks. There was no evidence of an effect on behavior nor ACTH-like endocrine actions such as elevated serum cortisol levels. Transdermal drug delivery studies performed in vitro showed reproducible diffusion of the NDP-MSH analog through full-thickness mouse skin. Approximately 0.002% to 0.05% of a 10(-4) M preparation was transdermally delivered using a DMSO/water solution or a PEG/alcohol cream base, respectively. This superpotent analog is now entering a Phase I clinical trial with possible therapeutic applications for the treatment of hypomelanotic disorders such as vitiligo and for pharmacologic tanning without the need for sunlight exposure.
Study Information
pubmed
1988
10.1007/bf00173642