Recent Advances in the Visualization and Quantification of Benzodiazepine Receptors

Abstract

The anxiolytic, hypnotic, anticonvulsant and muscle relaxant effects of the benzodiazepines are mediated by the inhibitory neurotransmitter GABA (γ-aminobutyric acid). The benzodiazepines modulate, in a facilitatory way, GABAergic transmission in a variety of principle output neurons and interneurons in the mammalian CNS (see Haefely, 1983 for a current review). These are receptor-mediated effects. Specific, high-affinity, saturable binding sites for the benzodiazepines form part of an oligomeric complex with a GABA receptor and its associated chloride channel protein (Möhler and Richards, 1983; Braestrup and Nielsen, 1983). Recent studies of the pharmacology and binding characteristics of the benzodiazepine receptor ligands have revealed a whole spectrum of compounds with a high affinity for the receptor but with different functional consequences (Haefely et al., 1984). Thus, three basic types of ligands can now be distinguished: agonists, which produce the characteristic therapeutic effects of the benzodiazepines; inverse agonists, which produce diametrically opposite effects to those of agonists; and competitive antagonists, which have no major intrinsic activity per se but prevent or abolish receptor-mediated pharmacological effects of agonists and inverse agonists (Figure 1). The receptor ligands could influence, allosterically, either the affinity of GABA for its receptor or the coupling between the GABA receptor and the chloride channel. Mixed agonists/antagonists (so-called partial agonists) are novel receptor ligands whose potential anxioselectivity is now being clinically evaluated.