Flavonoids as GABAA receptor ligands: the whole story?

WASOWSKI, CRISTINA; MARDER MARIEL

Journal of Experimental Pharmacology

Dove Press

Año: 2012 vol. 4 p. 9 - 24

1179-1454

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. They exert their therapeutic effects via binding to the BDZ binding site (BDZ-bs) of the gamma-aminobutyric acid type A receptors (GABAA-Rs), and allosterically modulating the chloride flux through the ion channel complex. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have been shown to possess selective affinity for BDZ-bs with a broad spectrum of central nervous system effects. Since the initial search for alternative BDZ ligands amongst the flavonoids, a list of successful synthetic derivatives has been generated with enhanced activities. This review describes an update on research developments that have established the activity of natural and synthetic flavonoids on the GABAA-Rs. Flavonoids are prominent drugs to treat mental disorders that also can be used as tools to study the modulatory sites at GABAA-Rs and to further develop GABAA subtype-selective agents.