Pharmacological characterization of 6-bromo-3'-nitroflavone, a synthetic flavonoid with high affinity for the benzodiazepine receptors.
6-Bromo-3'-nitroflavone is a synthetic flavone derivative that selectively recognizes benzodiazepine receptors and has potent anxiolytic-like effects. Here, we describe in detail its pharmacological characterization. When i.p. injected in mice, 6-bromo-3'-nitroflavone (0.01-0.3 mg/kg) had an anxiolytic-like effect in the elevated plus-maze test. This effect was blocked by the specific benzodiazepine receptor antagonist, flumazenil. In addition, it exhibited anxiolytic-like actions when given orally (1 mg/kg). 6-Bromo-3'-nitroflavone did not exhibit myorelaxant effects (up to 30 mg/kg, i.p.). Unlike diazepam, this flavonoid produced no anterograde amnesia in a one-trial inhibitory avoidance learning. On the other hand, 6-bromo-3'-nitroflavone possessed mild anticonvulsant activity (0.1 mg/kg, i.p.) and provoked sedative-depressant actions only at doses 100-1000 times higher than those producing anxiolytic-like effects. 6-Bromo-3'-nitroflavone (0.1-1 mM) produced a lower potentiation of gamma-amino-butyric acid (GABA)-stimulated 36Cl- influx (126-138%) in comparison to diazepam (0.1 mM: 166%) in cerebral cortical membrane vesicles. Taken together, these findings suggest that 6-bromo-3'-nitroflavone has anxiolytic-like action possibly behaving as a partial agonist of the benzodiazepine receptors.
Instituto de Biología Celular y Neurociencias, Facultad de Medicina, Buenos Aires, Argentina.
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Wolfman
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Viola
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Marder
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Ardenghi
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Wasowski
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Schröder
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Izquierdo
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Rúveda
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Paladini
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Medina
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D058785:GABA-A Receptor Agonists; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D012890:Sleep / Q000187:drug effects / Q000502:physiology
C115897:6-bromo-3'-nitroflavone; D014151:Anti-Anxiety Agents; D005419:Flavonoids; D058785:GABA-A Receptor Agonists; D010424:Pentobarbital; D010433:Pentylenetetrazole