4-amino-5-substituted-3(2H)-pyridazinones as orally active antinociceptive agents: synthesis and studies on the mechanism of action.

摘要: A number of 4-amino-5-vinylpyridazinones and 4-amino-5-heterocyclic-pyridazinones were synthesized tested for their analgesic activity. Many these compounds, at doses 3-20 mg kg -1 po, showed good antinociceptive activity, reducing by more than 50% the writhes with respect to controls. Compounds 16c, 19a, 20a, 28 most potent series because they able induce a effect dose 3 po. None active compounds provoked any visible change in normal behavior, as demonstrated rotarod test. Studies on mechanism action that analgesia induced was completely prevented pretreatment α 2 -antagonist yohimbine, suggesting an involvement -adrenoceptors. Further investigation indirect activation noradrenergic system through amplification noradrenaline release.