Primary pharmaco-toxicological evaluation of 2-iodomelatonin, a potent melatonin agonist.
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.
Stankov
B
B
Chair of Chemotherapy, University of Milan, Italy.
Gervasoni
M
M
Scaglione
F
F
Perego
R
R
Cova
D
D
Marabini
L
L
Fraschini
F
F
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
D007986:Luteinizing Hormone; C044556:2-iodomelatonin; D008550:Melatonin