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.