6,3 '-dibromoflavone and 6-nitro-3 '-bromoflavone: New additions to the 6,3 '-disubstituted flavone family of high-affinity ligands of the brain benzodiazepine binding site with agonistic properties

6,3'-Dibromoflavone and 6-nitro-3'-bromoflavone inhibited [H-3]flunitrazepa m binding to the benzodiazepine binding site of the gamma amino butyric aci d receptor complex with K-i values between 17 and 36 nM in different brain regions. Their gamma amino butyric acid ratio for [H-3]flunitrazepam bindin g to cerebral cortex membranes indicated partial agonistic proper ties. Bot h compounds had similar pharmacological effects: they produced anxiolytic-l ike effects at low doses but did not alter locomotor activity or muscle ton icity; sedation was caused only at doses higher than 30 mg/kg in mice. Thes e synthetic flavone derivatives join an existing family of 6,3'-disubstitut ed flavone compounds with high affinity for the benzodiazepine binding site and partial agonistic profiles. (C) 2000 Academic Press.