CHARACTERIZATION OF THE BINDING AND COMPARISON OF THE DISTRIBUTION OFBENZODIAZEPINE RECEPTORS LABELED WITH [H-3] DIAZEPAM AND [H-3] ALPRAZOLAM

The binding characteristics of [H-3]diazepam and [H-3]alprazolam were obtained by in vitro analysis of sections of rat brain. Dissociation, association, and saturation analyses were performed to optimize the co nditions for obtaining selective labeling of benzodiazepine receptors with the two tritiated compounds. Both drugs approached equilibrium ra pidly in vitro. Rosenthal analysis (Scatchard plot) of the saturation data indicated a similar finite number of receptors was being occupied by both ligands. Competition studies, using various ligands to inhibi t both [H-3]diazepam and [H-3]alprazolam indicated that these two comp ounds bind to the tissue sections as typical benzodiazepine drugs and apparently do not overlap onto other subtypes of receptors. These expe riments were performed by both binding assay in tissue sections and by light microscopic autoradiography. The major difference between the l abeling of the two compounds is represented by the peripheral benzodia zepine sites, which are recognized by [H-3]diazepam, but not occupied by [H-3]alprazolam (at nanomolar concentrations). This difference was readily apparent in the autoradiograms. Other pharmacokinetic or pharm acodynamic properties must distinguish these two benzodiazepines.