[(3)H]Flumazenil binding in the human hippocampal formation, frontal cortex and cerebellum detected by...

The pharmacological characterisation of the benzodiazepine binding site associated with the gamma-aminobutyric acid (GABA(A)) receptor in human brain has been demonstrated using in situ radioligand binding and autoradiography. The use of high-resolution phosphorimaging has allowed both the affinity (K(d)) and density (B(max)) of [(3)H]flumazenil binding to be measured within regions of the hippocampal formation as well as the cerebellum and frontal cortex. The Scatchard plots of data from all brain regions were linear with Hill coefficients close to unity consistent with the presence of a single binding site for [(3)H]flumazenil. The affinities of [(3)H]flumazenil binding within all the brain regions were similar (K(d) 1.57+/-0.20-3.08+/-0.01 nM), while the density of [(3)H]flumazenil binding varied significantly between the brain regions analysed (B(max) 182.7+/-7.3-596.7+/-34.0 fmol/mg ETE; P<0.0001). In conclusion, the present results indicate that in situ radioligand binding and high-resolution phosphorimaging techniques can be utilized to measure the distribution, density and affinity of [(3)H]flumazenil to the GABA(A) receptor within the human frontal cortex, cerebellum and hippocampal formation.