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 [(3)H]flunitrazepam binding to the benzodiazepine binding site of the gamma amino butyric acid receptor complex with K(i) values between 17 and 36 nM in different brain regions. Their gamma amino butyric acid ratio for [(3)H]flunitrazepam binding to cerebral cortex membranes indicated partial agonistic properties. Both compounds had similar pharmacological effects: they produced anxiolytic-like effects at low doses but did not alter locomotor activity or muscle tonicity; sedation was caused only at doses higher than 30 mg/kg in mice. These synthetic flavone derivatives join an existing family of 6,3'-disubstituted flavone compounds with high affinity for the benzodiazepine binding site and partial agonistic profiles.
Viola
H
H
Facultad de Medicina, Instituto de Biología Celular y Neurociencias, Paraguay 2155, Buenos Aires, (1121), Argentina.
Marder
M
M
Wasowski
C
C
Giorgi
O
O
Paladini
A C
AC
Medina
J H
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
C411896:6,3'-dibromoflavone; C411897:6-nitro-3'-bromoflavone; D005419:Flavonoids; D008024:Ligands; D011963:Receptors, GABA-A