GABAA receptors are important targets for therapeutic agents that work in the brain: they’re involved in cognition, vision, and circadian rhythms, as well as disorders like epilepsy, schizophrenia, and Alzheimer’s disease. The commonly prescribed benzodiazepines are an important class of positive GABAA receptor modulators, but come with numerous side effects including sedation, rebound anxiety, and amnesia. However, compounds that bind specific GABAA receptor subtypes and at sites other than the classical benzodiazepine site may yield new drugs with fewer side effects.
Mary Chebib and colleagues, The University of Sydney, Australia, discovered that isoflavones are potent modulators of human recombinant α1β2γ2L receptors. The team’s structure-driven design approach led to three lead molecules that are particularly efficacious and thus attractive candidates for further investigating subtype-specific modulation of GABAA receptors for treating neurological disorders.
- Identification of Benzopyran-4-one Derivatives (Isoflavones) as Positive Modulators of GABAA Receptors,
N. Gavande, N. Karim, G. A. R. Johnston, J. R. Hanrahan, M. Chebib,
ChemMedChem 2011, 6 (8).