Anxioselective properties of 6,3'-dinitroflavone, a high affinity benzodiazepine receptor ligand.

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

EUROPEAN JOURNAL OF PHARMACOLOGY

Año: 1996 vol. 318 p. 23 - 30

0014-2999

6,3´-Dinitroflavone is a synthetic flavone derivative with high affinity for central benzodiazepine receptors that has anxiolytic effects. Here, we describe its biochemical and pharmacological characterization. 6,3´-Dinitroflavone inhibited differentially 3Hxflunitrazepam binding to central benzodiazepine receptors in several brain regions, showing a lower Ki value in the cerebellum central benzodiazepine receptor type I-enriched area., and a higher Ki value in the spinal cord and in the dentate gyruscentral benzodiazepine receptor type II-enriched area.. When i.p. injected in mice, 6,3´-dinitroflavone had a potent anxiolytic effect in the elevated plus maze test. This effect was blocked by the specific central benzodiazepine receptor antagonist, Ro 15-1788. 6,3´-Dinitroflavone did not exhibit anticonvulsant or myorelaxant effects in mice or amnestic effects in rats. Moreover, it abolished the myorelaxant effect of diazepam. On the other hand, 6,3´-dinitroflavone possessed a mild sedative action only at doses 100–300-fold greater 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.-Dinitroflavone is a synthetic flavone derivative with high affinity for central benzodiazepine receptors that has anxiolytic effects. Here, we describe its biochemical and pharmacological characterization. 6,3´-Dinitroflavone inhibited differentially 3Hxflunitrazepam binding to central benzodiazepine receptors in several brain regions, showing a lower Ki value in the cerebellum central benzodiazepine receptor type I-enriched area., and a higher Ki value in the spinal cord and in the dentate gyruscentral benzodiazepine receptor type II-enriched area.. When i.p. injected in mice, 6,3´-dinitroflavone had a potent anxiolytic effect in the elevated plus maze test. This effect was blocked by the specific central benzodiazepine receptor antagonist, Ro 15-1788. 6,3´-Dinitroflavone did not exhibit anticonvulsant or myorelaxant effects in mice or amnestic effects in rats. Moreover, it abolished the myorelaxant effect of diazepam. On the other hand, 6,3´-dinitroflavone possessed a mild sedative action only at doses 100–300-fold greater 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.