PRIMARY PHARMACOTOXICOLOGICAL EVALUATION OF 2-IODOMELATONIN, A POTENTMELATONIN AGONIST

Series of experiments aimed at a primary pharmaco-toxicological evalua tion of 2-iodomelatonin, a high-affinity melatonin analogue, were perf ormed. In the rat ovulation-inhibition model, 2-iodomelatonin was much more potent than either melatonin or 6-chloromelatonin. The acute tox icity was extremely low and close to, though slightly higher than that reported previously for melatonin. In the rat, 2-iodomelatonin was sl owly metabolized in vivo; its apparent elimination half-life was about 60 minutes, much longer than that reported for melatonin. The in vitr o mutagenesis tests demonstrated clearly that 2-iodomelatonin in conce ntrations, exceeding the dose range employed in the in vivo studies, w as actually devoid of mutagenic effects. The obtained results suggest that 2-iodomelatonin deserves a detailed pharmaco-toxicological evalua tion and could be eventually used in pharmacokinetic and pharmacodynam ic studies in humans.