Pharmacological characterization of 6-bromo-3'-nitroflavone, a synthetic flavonoid with high affinity for the benzodiazepine receptors

Pharmacology Biochemistry and Behavior

Volumn 61, Issue 3, 1998, Pages 239-246

  Wolfman, C ^a   Viola, H ^a   Marder, M ^b   Ardenghi, P ^c   Wasowski, C ^b   Schroder N ^c   Izquierdo, I ^c   Ruveda E ^d   Paladini, A ^b   Medina, J H ^a  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^b Instituto de Quimica y Fisicoquimica Biologicas Buenos Aires   (Argentina)

^c FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^d Universidad Nacional de Rosario   (Argentina)

Author keywords

Agonist; Anxiety; Benzodiazepine receptors; Flavonoids; Sedation

Indexed keywords

6 BROMO 3' NITROFLAVONE; BENZODIAZEPINE RECEPTOR; BENZODIAZEPINE RECEPTOR BLOCKING AGENT; DIAZEPAM; FLAVONOID; FLUMAZENIL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTICONVULSANT ACTIVITY; ANXIETY; ARTICLE; BEHAVIOR; CONTROLLED STUDY; DRUG ACTIVITY; INTRAPERITONEAL DRUG ADMINISTRATION; LOCOMOTION; MALE; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RECEPTOR AFFINITY; SEDATION; SEIZURE; TRANQUILIZING ACTIVITY;

ANIMALS; ANTI-ANXIETY AGENTS; AVOIDANCE LEARNING; FLAVONOIDS; MALE; MAZE LEARNING; MICE; MOTOR ACTIVITY; PENTOBARBITAL; PENTYLENETETRAZOLE; PSYCHOMOTOR PERFORMANCE; RECEPTORS, GABA-A; SEIZURES; SLEEP;

EID: 0031767342     PISSN: 00913057     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0091-3057(98)00088-4     Document Type: Article

References (36)

1. Anca, J. M.; Lamela, M.; Gato, M. A.; Cadavid, I.; Calleja, J. M.: Activity on the central nervous system of Himanthalia elongata, part II. Planta Med. 59:101-105; 1992.
2. 3H]phorbol dibutyrate binding to PKC in selective regions of the rat brain. Brain Res. 685:163-168; 1995.
3. Bonetti, E. P.; Pierri, E. L.; Cumin, R.; Schaffner, M.; Gamzu, E. R.; Muller, R.; Haefely, W.: Benzodiazepine antagonist RO 15-1788: Neurological and behavioral effects. Psychopharmacology (Berlin) 78:8-18; 1982.
4. 3H]AMPA receptor binding in the hippocampal formation. Neurobiol. Learn. Mem. 64:257-262; 1995.
5. Dalvi, A.; Rodgers, R. J.: GABAergic influences on plus-maze behaviour in mice. Psychopharmacology (Berlin) 128:380-397; 1996.
6. Dawson, G. R.; Tricklebank, M. D.: Use of the elevated plus maze in the search for novel anxiolytic agents. Trends Pharmacol. Sci. 16:33-36; 1995.
7. Facklam, M.; Schoch, P.; Haefely, W. E.: Relationship between benzodiazepine receptor occupancy and potentiation of γ-aminobutyric acid-stimulated chloride flux in vitro of four ligands of differing intrinsic efficacies. J. Pharmacol. Exp. Ther. 261:1106-1112; 1992.
8. File, S. E.: What can be learned from the effects of benzodiazepine on exploratory behavior? Neurosci. Biobehav. Rev. 9:45-54; 1985.
9. A receptors and anxiety: From neurobiology to treatment. New York: Raven Press; 1995:93-113.
10. File, S. E.; Pellow, P.: The effects of triazolobenzodiazepines in two animal tests of anxiety and in the holeboard. Br. J. Pharmacol. 86:729-735; 1985.
11. File, S. E.; Fellow, S.: Intrinsic actions of the benzodiazepine receptor antagonist RO 15-1788. Psychopharmacology (Berlin) 88:1-11; 1986.
12. Haberlein, H.; Tschiersch, K. P.; Schafer, H.: Flavonoids from Leptospermum scoparium with affinity for the benzodiazepine receptor characterized by structure activity relationships and in vivo studies of a plant extract. Pharmazie 49:912-917; 1994.
13. Izquierdo, I.; Da Cunha, C.; Huang, C.; Walz, R.; Wolfman, C.; Medina, J. H.: Posttraining downregulation of memory consolidation by a GABA-A mechanism in the amygdala modulated by endogenous benzodiazepines. Behav. Neural Biol. 54:105-109; 1994.
14. Lister, R. G.: The use of a plus maze to measure anxiety in the mouse. Psychopharmacology (Berlin) 92:180-185; 1987.
15. Marder, M.; Viola, H.; Wasowski, C.; Wolfman, C.; Waterman, P. G.; Medina, J. H.; Paladini, A. C.: 6, 3′-Dinitroflavone, a novel high affinity ligand for the benzodiazepine receptor with potent anxiolytic properties. Bioorg. Med. Chem. Lett. 5:2717-2721; 1995.
16. Marder, M.; Viola, H.; Wasowski, C.; Wolfman, C; Waterman, P. G.; Cassels, B. K.; Medina, J. H.; Paladini, A. C.: 6-Bromoflavone, a high affinity ligand for the central benzodiazepine receptors is a member of a family of active flavonoids. Biochem. Biophys. Res. Commun. 223:384-391; 1996.
17. McKernan, R. M.; Whiting, P. J.: Which GABA-A receptors subtypes really occur in the brain? Trends Neurosci. 19:139-143; 1996.
18. Medina, J. H.; Paladini, A. C.: Occurrence of benzodiazepine, benzodiazepine-like molecules, and other ligands for the benzodiazepine receptor in nature. In: Izquierdo, I.; Medina, J. H., eds. Naturally occurring benzodiazepines. Chichester, UK: Ellis Horwood Ltd.; 1993:28-38.
19. Medina, J. H.; Paladini, A. C.; Wolfman, C.; Levi de Stein, M.; Calvo, D.; Diaz, I.; Peña, C.: Chrysin (5-7 di OH flavone), a naturally occurring ligand for benzodiazepine receptors with anticonvulsant properties. Biochem. Pharmacol. 40:2227-2232; 1990.
20. Medina, J. H.; Viola, H.; Wolfman, C.; Marder, M.; Wasowski, C.; Calvo, D.; Paladini, A. C.: Flavonoids: A new family of benzodiazepine receptor ligands. Neurochem. Res. 22:419-425; 1997.
21. 3H]flunitrazepam binding sites. J. Neurochem. 49:890-896; 1987.
22. Okuyama, E.; Okamoto, Y.; Yamazaki, M.; Satake, M.: Pharmacologically active components of a Peruvian medicinal plant, Huanarpo (Jathropa ciliata, M. Arg.). Chem. Pharm. Bull. (Jpn.) 44:333-336; 1994.
23. Pellow, S.; File, S.: Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus maze. A novel test of anxiety in the rat. Pharmacol. Biochem. Behav. 24: 525-529; 1986.
24. Pellow, S.; File, S. E.: Evidence that β-carboline, ZK 91296, can reduce anxiety in animals at doses below those causing sedation. Brain Res. 363:174-177; 1986.
25. Pellow, S.; Chopin, P.; File, S.; Briley, M.: Validation of open:closed arm entries in an elevated plus maze as measure of anxiety in the rat. J. Neurosci. Methods 14:149-167; 1985.
26. Potokar, J.; Nutt, D. J.: Anxiolytic potential of benzodiazepine receptor partial agonists. CNS Drugs 4:305-315; 1994.
27. Rolland, A.; Fleuretin, J.; Lanhers, M. C.; Younos, C.; Misslin, R.; Mortier, F.; Pelt, J. M.: Behavioural effects of the American traditional plant Eschscholzia californica: Sedative and anxiolytic properties. Planta Med. 57:212-216; 1991.
28. 3H]diazepam binding to rat brain membranes in vitro by dinatin and skrofulein. Acta Pharmacol. Sin. 15:385-388; 1994.
29. - ion channels modulated by multiple drug-binding sites. Trends Pharmacol. Sci. 13:446-450; 1992.
30. Sternbach, L. H.: The benzodiazepine story. Prog. Drug Res. 22:229-266; 1978.
31. Viola, H.; Wolfman, C.; Levi de Stein, M.; Wasowski, C.; Peña, C.; Medina, J. H.; Paladini, A. C.: Isolation of pharmacologically active benzodiazepine receptor ligand from Tilia tomentosa (Tiliaceae). J. Etnopharmacol. 44:47-53; 1994.
32. Viola, H.; Wasowski, C.; Levi de Stein, M.; Wolfman, C.; Silveira, R.; Dajas, F.; Medina, J. H.; Paladini, A. C.: Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med. 61:213-218; 1995.
33. Viola, H.; Marder, M.; Wolfman, C.; Wasowski, C.; Medina, J. H.; Paladini, A. C.: 6-Bromo-3′-nitroflavone, a new high affinity benzodiazepine receptor agonist recognizes two populations of cerebral cortical binding sites. Bioorg. Med. Chem. Lett. 7:373-378; 1997.
34. Wisden, W.; Laurie, D. J.; Monyer, H.; Seeburg, P.: The distribution of 13 GABA-A receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J. Neurosci. 12: 1040-1050; 1992.
35. Wolfman, C.; Viola, H.; Paladini, A. C.; Dajas, F.; Medina, J. H.: Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol. Biochem. Behav. 47:1-4; 1994.
36. Wolfman, C.; Viola, H.; Marder, M.; Wasowski, C.; Ardenghi, P.; Izquierdo, I.; Paladini, A. C.; Medina, J. H.: Anxioselective properties of 6, 3′-dinitroflavone, a high-affinity benzodiazepine receptor ligand. Eur. J. Pharmacol. 318:23-29; 1996.