A number of 4-amino-5-vinylpyridazinones and 4-amino-5-heterocyclic-pyridazinones were synthesized and tested for their analgesic activity. Many of these compounds, tested at doses of 3-20 mg kg-1 po, showed good antinociceptive activity, reducing by more than 50% the number of writhes with respect to controls. Compounds 16c, 19a, 20a, and 28 were the most potent of the series because they were able to induce a potent antinociceptive effect at a dose of 3 mg kg-1 po. None of the active compounds at the analgesic dose provoked any visible change in normal behavior, as demonstrated in the rotarod test. Studies on the mechanism of action showed that the analgesia induced by the active compounds was completely prevented by pretreatment with the alpha2-antagonist yohimbine, suggesting an involvement of alpha2-adrenoceptors. Further investigation demonstrated an indirect activation of the noradrenergic system through an amplification of noradrenaline release.