Neuropharmacology of a new potential anxiolytic compound, F 2692, 1-(3'-trifluoromethyl phenyl) 1,4-dihydro 3-amino 4-oxo 6-methyl pyridazine. 1. Acute and in vitro effects.
F 2692 [1-(3'-trifluoromethyl phenyl) 1,4-dihydro 3-amino 4-oxo 6-methyl pyridazine] exhibited dose-dependent "anxiolytic" properties in the elevated plus-maze and the punished drinking tests in rats. It was also active in the two-compartment test in mice. The "anxiolytic" effects were antagonised by the benzodiazepine antagonists, flumazenil and ZK 93426. The compound exhibited anticonvulsant, sedative, myorelaxant and amnesic effects at doses 3-30 times higher than those required for "anxiolytic" activity. F 2692 has a very low affinity for benzodiazepine binding sites in vitro and in vivo (about 1000 and 160 fold lower than diazepam respectively). In addition it displayed no affinity for GABAA, alpha 2-adrenergic, 5-HT1A or 5-HT2 receptors. These data suggest that F 2692 may be a potential anxiolytic compound with an unusual mechanism of action.
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Centre de Recherche Pierre Fabre, Castres, France.
Chopin
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Stenger
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A
Palmier
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C
Briley
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D001667:Binding, Competitive / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005445:Flunitrazepam / Q000493:pharmacokinetics; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D016548:Prosencephalon / Q000378:metabolism; D011724:Pyridazines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012890:Sleep / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D009125:Muscle Relaxants, Central; D011724:Pyridazines; C077138:F 2692; D005445:Flunitrazepam