Toxicologic studies of a superpotent alpha-melanotropin, [Nle4, D-Phe7]alpha-MSH.
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.
Dorr
R T
RT
Department of Internal Medicine, University of Arizona, Tucson 85724.
Dawson
B V
BV
al-Obeidi
F
F
Hadley
M E
ME
Levine
N
N
Hruby
V J
VJ
D000279:Administration, Cutaneous; D000818:Animals; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000235:genetics; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-