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

Eur J Pharmacol. 1996 Dec 27;318(1):23-30. doi: 10.1016/s0014-2999(96)00784-4.

Abstract

6,3'-Dintroflavone 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 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Autoradiography
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Flavonoids / pharmacology*
  • Flunitrazepam / pharmacology
  • Ligands
  • Male
  • Mice
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Anti-Anxiety Agents
  • Flavonoids
  • Ligands
  • Receptors, GABA-A
  • 3',6-dinitroflavone
  • Flunitrazepam