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 [(3)H]flunitrazepam binding to the benzodiazepine binding site of the GABA(A) receptor (BDZ-bs) with Ki values between 10 and 50 nM in different brain regions. The GABA ratio of 1.03 for [(3)H]flunitrazepam binding to cerebral cortex, 0.76 for cerebellum, 0.7 for hippocampus, 0.7 for striatum, and 0.8 for spinal cord indicated an antagonistic or weak inverse agonistic profile of 6-methyl-3'-bromoflavone on BDZ-bs. Unlike classical benzodiazepines, it had no anticonvulsant, anxiolytic, myorelaxant, sedative, amnestic or motor incoordination effects. However, it antagonized the muscle relaxant, the sedative effect, and the changes in locomotor activity induced by diazepam. Taken together, these findings suggest that 6-methyl-3'-bromoflavone has an antagonistic profile on the BDZ-bs.
Viola
H
H
Facultad de Medicina, Instituto de Biología Celular, Paraguay 2155 (1121), Buenos Aires, Argentina.
Marder
M
M
Nuñez
J
J
Izquierdo
L
L
Wasowski
C
C
Wolfman
C
C
Ardenghi
P
P
Barros
D
D
Medina
J H
JH
Paladini
A C
AC
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005445:Flunitrazepam / Q000493:pharmacokinetics; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
C121566:6-methyl-3'-bromoflavone; D005419:Flavonoids; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D011963:Receptors, GABA-A; D005445:Flunitrazepam