Pharmacological Characterization of 6-Bromo-3′-nitroflavone, a Synthetic Flavonoid with High Affinity for the Benzodiazepine Receptors

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1998-11, Vol.61 (3), p.239-246
• Main Authors: Wolfman, C., Viola, H., Marder, M., Ardenghi, P., Wasowski, C., Schröder, N., Izquierdo, I., Rúveda, E., Paladini, A., Medina, J.H.
• Format: Article
• Language: English
• Subjects: Agonist; Animals; Anti-Anxiety Agents - pharmacology; Anxiety; Avoidance Learning - drug effects; Avoidance Learning - physiology; Benzodiazepine receptors; Biological and medical sciences; Flavonoids; Flavonoids - pharmacology; Flavonoids - therapeutic use; GABA-A Receptor Agonists; Male; Maze Learning - drug effects; Maze Learning - physiology; Medical sciences; Mice; Motor Activity - drug effects; Motor Activity - physiology; Neuropharmacology; Pentobarbital - pharmacology; Pentylenetetrazole - pharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Sedation; Seizures - chemically induced; Seizures - drug therapy; Sleep - drug effects; Sleep - physiology
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(98)00088-4

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 IP 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, IP). 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, IP) 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 γ-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.