Pharmacological characterization of 6-bromo-3'-nitroflavone, a synthetic flavonoid with high affinity for the benzodiazepine receptors.

Abstract

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.

• Authors: C Wolfman, H Viola, M Marder, P Ardenghi, C Wasowski, N Schröder, I Izquierdo, E Rúveda, A Paladini, J H Medina
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 61 Issue 3 Pg. 239-46 (Nov 1998) ISSN: 0091-3057 [Print] United States
• PMID: 9768558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-bromo-3'-nitroflavone
• Anti-Anxiety Agents
• Flavonoids
• GABA-A Receptor Agonists
• Pentobarbital
• Pentylenetetrazole

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Avoidance Learning (drug effects, physiology)
• Flavonoids (pharmacology, therapeutic use)
• GABA-A Receptor Agonists
• Male
• Maze Learning (drug effects, physiology)
• Mice
• Motor Activity (drug effects, physiology)
• Pentobarbital (pharmacology)
• Pentylenetetrazole (pharmacology)
• Psychomotor Performance (drug effects)
• Seizures (chemically induced, drug therapy)
• Sleep (drug effects, physiology)