title: Primary pharmaco-toxicological evaluation of 2-iodomelatonin, a potent melatonin agonist.
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.
authors.affiliation: Chair of Chemotherapy, University of Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Stankov
authors.forename: M
authors.initials: M
authors.lastname: Gervasoni
authors.forename: F
authors.initials: F
authors.lastname: Scaglione
authors.forename: R
authors.initials: R
authors.lastname: Perego
authors.forename: D
authors.initials: D
authors.lastname: Cova
authors.forename: L
authors.initials: L
authors.lastname: Marabini
authors.forename: F
authors.initials: F
authors.lastname: Fraschini
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000633:toxicity; D009152:Mutagenicity Tests; D010060:Ovulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007986:Luteinizing Hormone; C044556:2-iodomelatonin; D008550:Melatonin