High affinity and stereospecific receptors for benzodiazepines are present in the mammalian central nervous system. It is currently believed that the interaction of benzodiazepines with their receptors initiates a series of neuronal events resulting in an enhancement of GABA-mediated choloride permeability. The latter results behaviorally in the major pharmacological actions of benzodiazepines, namely their anxiolytic, anticonvulsant, hypnotic, and muscle relaxant actions. In addition to benzodiazepines, a variety of sedative/hypnotic agents of the minor tranquilizer class (e.g., the barbiturates) appear to interact with one or more components of the benzodiazepine/GABA receptor complex, and thus the latter has been proposed as a common site of minor tranquilizer action. Several aspects of the benzodiazepine/GABA receptor complex are currently being studied, including purification of the receptor, characterization of multiple binding sites on the receptor complex which recognizes agonist, antagonists or inverse agonists. The development of anti-iodiotypic antibodies to the various binding site domains on the complex studies on the behavioral and biochemical effects of novel (non-benzodiazepine) anxiolytics as well as """"""""anxiogenic"""""""" inverse agonists, and the identification of a novel benzodiazepine receptor in the CNS and peripheral tissues for 4-chlorodiazepam (Ro5-4864), the so-called peripheral benzodiazepine receptor ligand. Recent work has also focused on using an in vitro system for measuring GABA receptor-effector coupling in a subcellular preparation from rat brain (the synaptoneurosome). This technique has greatly facilitated studies on barbiturate and GABA receptor-mediated chloride flux and has resulted in the first reliable method for studying the function of the GABA receptor in vitro.
