In Vivo Imaging of Benzodiazepine Receptors with Positron Emission Tomography

The benzodiazepines (BZs) are among the most frequently prescribed of all drugs in current use. In vitro studies on the mechanism of BZ action have revealed high affinity saturable binding sites in brain. There is good correlation between behavioral pharmacology and binding dose-response data, suggesting that the specific binding defined by classic BZ agonists such as ( 3 H)diazepam and ( 3 H)flunitrazepam reflects the site of BZ action in vivo. In vitro biochemical and electrophysiologic studies reveal interactions between BZs, barbiturates, and gamma-aminobutyric acid (GABA). The inhibitory action of GABA is mediated by enhancement of cell membrane chloride permeability. This effect is facilitated by addition of BZs or barbiturates. Drug discovery projects have identified ligands which interact with the BZ Receptors but which do not possess typical BZ physiologic or behavioral effects.