6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity

6-Chloro-3'-nitroflavone integrates a list of nearly 70 flavone derivatives synthesized in our laboratories. The effects of 6-chloro-3'- nitroflavone on the benzodiazepine binding sites (BDZ-BSs) of the GABA(A) receptor were examined in vitro and in vivo. 6-Chloro-3'-nitroflavone inhi...

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Detalles Bibliográficos
Autores principales: Viola, H., Wolfman, C., Marder, M., Goutman, J.D., Bianchin, M., Wasowski, C., Calvo, D.J., Izquierdo, I., Paladini, A.C., Medina, J.H.
Formato: JOUR
Materias:
Antagonist
Benzodiazepine binding site of the GABA(A) receptor
Flavonoids
6 chloro 3' nitroflavone
flavone derivative
nitrazepam
unclassified drug
animal experiment
animal model
article
binding site
brain membrane
controlled study
drug potency
drug receptor binding
electrophysiology
intrinsic sympathomimetic activity
ligand binding
motor coordination
nonhuman
priority journal
rat
receptor affinity
voltage clamp
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00913057_v65_n2_p313_Viola
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:6-Chloro-3'-nitroflavone integrates a list of nearly 70 flavone derivatives synthesized in our laboratories. The effects of 6-chloro-3'- nitroflavone on the benzodiazepine binding sites (BDZ-BSs) of the GABA(A) receptor were examined in vitro and in vivo. 6-Chloro-3'-nitroflavone inhibited the [3H]flunitrazepam ([3H]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 BDZ-BSs (GABA-shift = 1. 16 ± 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'-nitroflavone did not affect GABA(A)-receptors (GABA(A)-Rs) responses recorded in Xenopus oocytes expressing α1β2γ(2s) subunits, but blocked the potentiation exerted by diazepam (DZ) on GABA-activated chloride currents. In vivo experiments showed that 6-chloro-3'-nitroflavone did not possess anxiolytic, anticonvulsant, sedative, myorelaxant actions in mice or amnestic effects in rats; however, 6-chloro-3'-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'- nitroflavone behaves as an antagonist of the BDZ-BSs. (C) 2000 Elsevier Science Inc.

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