Anxioselective properties of 6,3'-dinitroflavone, a high-affinity benzodiazepine receptor ligand.
6,3'-Dintroflavone is a synthetic flavone derivative with high affinity for central benzodiazepine receptors that has anxiolytic effects. Here, we describe its biochemical and pharmacological characterization. 6,3'-Dinitroflavone inhibited differentially [3H]flunitrazepam binding to central benzodiazepine receptors in several brain regions, showing a lower Ki value in the cerebellum (central benzodiazepine receptor type I-enriched area), and a higher Ki value in the spinal cord and in the dentate gyrus (central benzodiazepine receptor type II-enriched area). When i.p. injected in mice, 6,3'-dinitroflavone had a potent anxiolytic effect in the elevated plus maze test. This effect was blocked by the specific central benzodiazepine receptor antagonist, Ro 15-1788. 6,3'-Dinitroflavone did not exhibit anticonvulsant or myorelaxant effects in mice or amnestic effects in rats. Moreover, it abolished the myorelaxant effect of diazepam. On the other hand, 6,3'-dinitroflavone possessed a mild sedative action only at doses 100-300-fold greater than the anxiolytic one. Based on these findings, we suggest that 6,3'-dinitroflavone has a benzodiazepine partial agonist profile, with low selectivity for central benzodiazepine receptor types I and II.
Wolfman
C
C
Instituo de Biología Celular, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
Viola
H
H
Marder
M
M
Wasowski
C
C
Ardenghi
P
P
Izquierdo
I
I
Paladini
A C
AC
Medina
J H
JH
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005445:Flunitrazepam / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D014151:Anti-Anxiety Agents; D005419:Flavonoids; D008024:Ligands; D011963:Receptors, GABA-A; C105566:3',6-dinitroflavone; D005445:Flunitrazepam