ANXIOSELECTIVE PROPERTIES OF 6,3'-DINITROFLAVONE, A HIGH-AFFINITY BENZODIAZEPINE RECEPTOR-LIGAND

6,3'-Dinitroflavone is a synthetic flavone derivative with high affini ty for central benzodiazepine receptors that has anxiolytic effects. H ere, we describe its biochemical and pharmacological characterization. 6,3'-Dinitroflavone inhibited differentially [H-3]flunitrazepam bindi ng to central benzodiazepine receptors in several brain regions, showi ng a lower K-i value in the cerebellum (central benzodiazepine recepto r type I-enriched area), and a higher K-i value in the spinal cord and in the dentate gyrus (central benzodiazepine receptor type II-enriche d area). When i.p. injected in mice, 6,3'-dinitroflavone had a potent anxiolytic effect in the elevated plus maze test. This effect was bloc ked by the specific central benzodiazepine receptor antagonist, Ro 15- 1788. 6,3'-Dinitroflavone did not exhibit anticonvulsant or myorelaxan t effects in mice or amnestic effects in rats. Moreover, it abolished the myorelaxant effect of diazepam. On the other hand, 6,3'-dinitrofla vone possessed a mild sedative action only at doses 100-300-fold great er than the anxiolytic one. Based on these findings, we suggest that 6 ,3'-dinitroflavone has a benzodiazepine partial agonist profile, with low selectivity for central benzodiazepine receptor types I and II.