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

C. WOLFMAN; H. VIOLA; M. MARDER; P. ARDENGHI; C. WASOWSKI; N. SCHRODER; I. IZQUIERDO; E. A. RÚVEDA; A. C. PALADINI; J. H. MEDINA

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Año: 1998 vol. 61 p. 239 - 246

0091-3057

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 g-amino-butyric acid (GABA)-stimulated 36 Cl 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.-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 g-amino-butyric acid (GABA)-stimulated 36 Cl 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.