6-methyl-3 '-bromoflavone, a high-affinity ligand for the benzodiazepine binding site of the GABA(A) receptor with some antagonistic properties

6-Methyl-3'-bromoflavone inhibited [H-3]flunitrazepam binding to the benzod iazepine binding site of the GABA(A) receptor (BDZ-bs) with Ki values betwe en 10 and 50 nM. in different brain regions,The GABA ratio of 1.03 for [H-3 ]flunitrazepam binding to cerebral cortex, 0.76 for cerebellum, 0.7 for hip pocampus, 0.7 for striatum, and 0.8 for spinal cord indicated an antagonist ic or weak inverse agonistic profile of 6-methyl-3'-bromoflavone on BDZ-bs. Unlike classical benzodiazepines, it had no anticonvulsant, anxiolytic, my orelaxant, sedative, amnestic or motor incoordination effects. However, it antagonized the muscle relaxant, the sedative effect, and the changes in lo comotor activity induced by diazepam. Taken together, these findings sugges t that 6-methyl-3'-bromoflavone has an antagonistic profile on the BDZ-bs. (C) 1999 Academic Press.