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

WOLFMAN, CLAUDIA; VIOLA, HAYDEÉ; MARDER, MARIEL; WASOWSKI, CRISTINA; ARDENGHI, PATRICIA; IZQUIERDO, IVÁN; PALADINI, ALEJANDRO C.; MEDINA, JORGE H.

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

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 [3H]flunitrazepam binding to central benzodiazepine receptors in several brain regions, showing a lower K(i) value in the cerebellum (central benzodiazepine receptor type I-enriched area), and a higher K(i) value in the spinal cord and in the dentate gyrus (central 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.