Primary pharmaco-toxicological evaluation of 2-iodomelatonin, a potent melatonin agonist

Life Sci. 1993;53(17):1357-65. doi: 10.1016/0024-3205(93)90596-u.

Abstract

Series of experiments aimed at a primary pharmaco-toxicological evaluation of 2-iodomelatonin, a high-affinity melatonin analogue, were performed. In the rat ovulation-inhibition model, 2-iodomelatonin was much more potent than either melatonin or 6-chloromelatonin. The acute toxicity was extremely low and close to, though slightly higher than that reported previously for melatonin. In the rat, 2-iodomelatonin was slowly metabolized in vivo; its apparent elimination half-life was about 60 minutes, much longer than that reported for melatonin. The in vitro mutagenesis tests demonstrated clearly that 2-iodomelatonin in concentrations, exceeding the dose range employed in the in vivo studies, was actually devoid of mutagenic effects. The obtained results suggest that 2-iodomelatonin deserves a detailed pharmaco-toxicological evaluation and could be eventually used in pharmacokinetic and pharmacodynamic studies in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • Luteinizing Hormone / metabolism
  • Male
  • Melatonin / analogs & derivatives*
  • Melatonin / metabolism
  • Melatonin / pharmacology
  • Melatonin / physiology*
  • Melatonin / toxicity
  • Mutagenicity Tests
  • Ovulation / drug effects
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Luteinizing Hormone
  • 2-iodomelatonin
  • Melatonin