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Viola, H.; Wolfman, C.; Marder, M.; Goutman, J.D.; Bianchin, M.; Wasowski, C.; Calvo, D.J.; Izquierdo, I.; Paladini, A.C.; Medina, J.H. "6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity" (2000) Pharmacology Biochemistry and Behavior. 65(2):313-320
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Abstract:

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.

Registro:

Documento: Artículo
Título:6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity
Autor:Viola, H.; Wolfman, C.; Marder, M.; Goutman, J.D.; Bianchin, M.; Wasowski, C.; Calvo, D.J.; Izquierdo, I.; Paladini, A.C.; Medina, J.H.
Filiación:Inst. de Biol. Cel. Y Neurosciencias, Fac. de Med., Paraguay 2155 (1121), Buenos Aires, Argentina
Inst. de Quim. Y Fisicoquimica Biol., Fac. Farmacia Y Bioquim., J., Buenos Aires, Argentina
Inst. Ing. Genet. Y Biol. Molec. C., Obligado 2490 (1428), Buenos Aires, Argentina
Centro de Memôria, Inst. Biociencias, Univ. Fed. Rio G., Porto Alegre, Brazil
Palabras clave: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
Año:2000
Volumen:65
Número:2
Página de inicio:313
Página de fin:320
DOI: http://dx.doi.org/10.1016/S0091-3057(99)00199-9
Título revista:Pharmacology Biochemistry and Behavior
Título revista abreviado:Pharmacol. Biochem. Behav.
ISSN:00913057
CODEN:PBBHA
CAS:nitrazepam, 146-22-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00913057_v65_n2_p313_Viola

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Citas:

---------- APA ----------
Viola, H., Wolfman, C., Marder, M., Goutman, J.D., Bianchin, M., Wasowski, C., Calvo, D.J.,..., Medina, J.H. (2000) . 6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity. Pharmacology Biochemistry and Behavior, 65(2), 313-320.
http://dx.doi.org/10.1016/S0091-3057(99)00199-9
---------- CHICAGO ----------
Viola, H., Wolfman, C., Marder, M., Goutman, J.D., Bianchin, M., Wasowski, C., et al. "6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity" . Pharmacology Biochemistry and Behavior 65, no. 2 (2000) : 313-320.
http://dx.doi.org/10.1016/S0091-3057(99)00199-9
---------- MLA ----------
Viola, H., Wolfman, C., Marder, M., Goutman, J.D., Bianchin, M., Wasowski, C., et al. "6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity" . Pharmacology Biochemistry and Behavior, vol. 65, no. 2, 2000, pp. 313-320.
http://dx.doi.org/10.1016/S0091-3057(99)00199-9
---------- VANCOUVER ----------
Viola, H., Wolfman, C., Marder, M., Goutman, J.D., Bianchin, M., Wasowski, C., et al. 6-Chloro-3'-nitroflavone is a potent ligand for the benzodiazepine binding site of the GABA(A) receptor devoid of intrinsic activity. Pharmacol. Biochem. Behav. 2000;65(2):313-320.
http://dx.doi.org/10.1016/S0091-3057(99)00199-9