Toxicologic studies of a superpotent α-melanotropin, [Nle4, D-Phe7]α-MSH

Robert T. Dorr, Brenda V. Dawson, Fahad Al-Obeidi, Mac E. Hadley, Norman Levine, Victor J. Hruby

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

A toxicology study was performed in mice given a superpotent α melanocyte stimulating hormone (MSH) analog. This 13 amino acid derivative, [Nle4, D-Phe7]α-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 α-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 10-4M 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.

Original languageEnglish (US)
Pages (from-to)251-258
Number of pages8
JournalInvestigational New Drugs
Volume6
Issue number4
DOIs
StatePublished - Dec 1 1988

Keywords

  • [NleD-Phe]α-MSH
  • toxicology
  • α-melanotropin

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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