6-Chlorine-3’-Nitroflavone is a potent central benzodiazepine receptor ligand devoid of intrinsic activity.

HAYDEÉ VIOLA; CLAUDIA WOLFMAN; MARIEL MARDER; JUAN D. GOUTMAN; CRISTINA WASOWSKY; DANIEL J. CALVO; IVÁN IZQUIERDO; ALEJANDRO C. PALADINI; JORGE H. MEDINA

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Año: 2000 vol. 65 p. 313 - 320

0091-3057

6-Chloro-3 9 -nitroflavone is a potent ligand for the benzodiazepine binding site of GABA A receptor devoid of intrinsic activity. PHARMACOL BIOCHEM BEHAV 65 (2) 313–320, 2000.—6-Chloro-3 9 -nitroflavone integrates a list of nearly 70 flavone derivatives synthesized in our laboratories. The effects of 6-chloro-3 9 -nitroflavone on the benzodiazepine binding sites (BDZ-BSs) of the GABA A receptor were examined in vitro and in vivo. 6-Chloro-3 9 -nitroflavone inhibited the [ 3 H]flunitrazepam ([ 3 H]FNZ) binding to rat cerebral cortex membranes with a K i of 6.68 nM and the addition of GABA to extensively washed membranes did not modify its affinity for the BDZBSs (GABA-shift 5 1. 16 6 0.12). The binding assays performed in rat striatal and cerebellar brain membranes showed that this compound has similar affinity to different populations of BDZ-BSs. Electrophysiological experiments revealed that 6-chloro-3 9 -nitroflavone did not affect GABA A -receptors (GABA A -Rs) responses recorded in Xenopus oocytes expressing a 1 b 2 g 2s subunits, but blocked the potentiation exerted by diazepam (DZ) on GABA-activated chloride currents. In vivo experiments showed that 6-chloro-3 9 -nitroflavone did not possess anxiolytic, anticonvulsant, sedative, myorelaxant actions in mice or amnestic effects in rats; however, 6-chloro-3 9 -nitroflavone antagonized diazepam-induced antianxiety action, anticonvulsion, short-term, and long-term amnesia and motor incoordination. These biochemical, electrophysiological, and pharmacological results suggest that 6-chloro-3 9 -nitroflavone behaves as an antagonist of the BDZ-BSs