GABAA receptor modulators as anxioselective anxiolytics

Benzodiazepines are effective anxiolytics whose use is limited by sedation, amnesia and myorelaxation, driving the search for novel, anxioselective GABAA receptor modulators. Preclinical data from ‘knock-in’ mice and α2,3-subunit selective GABAA receptor agonists suggest that these targets may yield anxioselective agents. In contrast, additional preclinical and clinical evidence suggests that a combination of mechanisms, including partial agonism and receptor subtype selectivity, will be required to achieve anxioselectivity in the clinic.

Section editors:David Sibley – National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USAC. Anthony Altar – Psychiatric Genomics, Gaithersburg, USATheresa Branchek – Lundbeck Research, Paramus, USA