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 selecti vely recognizes benzodiazepine receptors and has potent anxiolytic-lik e effects. Here, we describe in detail its pharmacological characteriz ation. 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 g iven orally (1 mg/kg). 6-Bromo-3'-nitroflavone did not exhibit myorela xant effects (up to 30 mg/kg, IF). Unlike diazepam, this flavonoid pro duced no anterograde amnesia in a one-trial inhibitory avoidance learn ing. On the other hand, 6-bromo-3'-nitroflavone possessed mild anticon vulsant activity (0.1 mg/kg, IP) and provoked sedative-depressant acti ons only at doses 100-1000 times higher than those producing anxiolyti c-like effects. 6-Bromo-3'-nitroflavone (0.1-1 mM) produced a lower po tentiation of gamma-amino-butyric acid (GABA)-stimulated Cl-36(-) infl ux (126-138%) in comparison to diazepam (0.1 mM: 166%) in cerebral cor tical 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. (C) 1998 Elsevier Science Inc.