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Overview—Flavonoids: A New Family of Benzodiazepine Receptor Ligands

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Abstract

Benzodiazepines (BDZs) are the most widely prescribed class of psychoactive drugs in current therapeutic use, despite the important unwanted side-effects that they produce such as sedation, myorelaxation, ataxia, amnesia, ethanol and barbiturate potentiation and tolerance. Searching for safer BDZ-receptor (BDZ-R) ligands we have recently demonstrated the existence of a new family of ligands which have a flavonoid structure. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have shown to possess a selective and relatively mild affinity for BDZ-Rs and a pharmacological profile compatible with a partial agonistic action. In a logical extension of this discovery various synthetic derivatives of those compounds, such as 6,3′-dinitroflavone were found to have a very potent anxiolytic effect not associated with myorelaxant, amnestic or sedative actions. This dinitro compound, in particular, exhibits a high affinity for the BDZ-Rs (Ki = 12–30 nM). Due to their selective pharmacological profile and low intrinsic efficacy at the BDZ-Rs, flavonoid derivatives, such as those described, could represent an improved therapeutic tool in the treatment of anxiety. In addition, several flavone derivatives may provide important leads for the development of potent and selective BDZ-Rs ligands.

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Authors and Affiliations

  1. Instituto de Biologia Celular y Neurociencias, Facultad de Medicina, UBA, Paraguay 2155, (, 1121), Buenos Aires, Argentina

    Jorge H. Medina, Haydee Viola, Claudia Wolfman & Daniel Calvo

  2. Instituto de Quimica y Fisicoquimica Biologicas, Facultad de Farmacia y Bioquimica, UBA, Junin 956, (, 1113), Buenos Aires, Argentina

    Mariel Marder, Cristina Wasowski & Alejandro C. Paladini

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  1. Jorge H. Medina
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  2. Haydee Viola
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  3. Claudia Wolfman
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  4. Mariel Marder
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  5. Cristina Wasowski
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  6. Daniel Calvo
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  7. Alejandro C. Paladini
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Medina, J.H., Viola, H., Wolfman, C. et al. Overview—Flavonoids: A New Family of Benzodiazepine Receptor Ligands. Neurochem Res 22, 419–425 (1997). https://doi.org/10.1023/A:1027303609517

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