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

• Published in: European journal of pharmacology Vol. 318; no. 1; pp. 23 - 30
• Main Authors: Wolfman, Claudia, Viola, Haydeé, Marder, Mariel, Wasowski, Cristina, Ardenghi, Patricia, Izquierdo, Iván, Paladini, Alejandro C, Medina, Jorge H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 27-12-1996; Elsevier
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Anxiolysis; Autoradiography; Behavior, Animal - drug effects; Benzodiazepine receptor; Biological and medical sciences; Brain - drug effects; Brain - metabolism; central; Central Nervous System - drug effects; Central Nervous System - metabolism; Flavonoid; Flavonoids - pharmacology; Flunitrazepam - pharmacology; Ligands; Male; Medical sciences; Mice; Neuropharmacology; Partial agonist; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Receptors, GABA-A - drug effects; Spinal Cord - drug effects; Spinal Cord - metabolism; Partial agonist; Autoradiography; Anxiolysis; Benzodiazepine receptor; Flavonoid; Flavones; Rat; Psychotropic; Rodentia; Central nervous system; In vitro; Vertebrata; Mammalia; Tranquillizer; Animal; Mechanism of action; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00784-4

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.