Enhancement of GABA binding by benzodiazepines and related anxiolytics

Several benzodiazepines (chlordiazepoxide, clonazepam, diazepam, midazolam, nitrazepam and oxazepam) produced a concentration-dependent enhancement of low affinity GABA binding to fresh, washed brain membranes in 50 mM Tris-citrate buffer at concentrations comparable to those displacing [3H]diazepam binding in vitro. The nonbenzodiazepine anxiolytics CL218872 and zopiclone also enhanced GABA binding, while the centrally inactive benzodiazepine Ro5-4864 failed to alter GABA binding. The benzodiazepine antagonist, Ro15-1788 did not alter GABA binding but potently antagonised stimulation of GABA binding by 100 nM diazepam. These pharmacological characteristics suggest that an enhancement of the binding of GABA to low affinity receptor sites may give rise to many of the in vivo actions of the benzodiazepines.