Synthesis of new serotonergic 2-substituted 4,6-diaryl pyridazin-3-ones.
A series of 4,6-diaryl pyridazin-3-ones substituted in the 2-position by [4-(4-aryl piperazin-1-yl]-but-2-ynyl moieties was synthesized and evaluated for antidepressant activity. The structures of these new pyridazine derivatives were confirmed by IR, 1H-NMR spectra and by elementary analysis. At 150 mg/kg i.p., they induced little or no reduction of the duration of immobility of mice in the forced swimming test. Head twitches produced by L-5-hydroxytryptophan in mice pretreated with pargyline were significantly potentiated by most of the tested compounds. In addition, pyridazine derivatives did not antagonize reserpine-induced palpebral ptosis or enhance the toxic effects of yohimbine and were almost devoid of anticholinergic properties in mice.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001763:Blepharoptosis / Q000139:chemically induced / Q000517:prevention & control; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009184:Mydriatics / Q000633:toxicity; D010095:Oxotremorine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012110:Reserpine; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D015016:Yohimbine / Q000633:toxicity
D018721:Muscarinic Agonists; D009184:Mydriatics; D011724:Pyridazines; D018490:Serotonin Agents; D015016:Yohimbine; D010095:Oxotremorine; D012110:Reserpine; D006916:5-Hydroxytryptophan