The present status of benzodiazepines in psychopharmacology.

The benzodiazepines continue to offer many challenging questions for the pharmacologist. For example, do the various different properties exhibited by benzodiazepines, notably the sedative, anxiolytic and anticonvulsant effects, reflect aspects of a single common mechanism of action, or are these properties dissociable? To what extent to chemically unrelated drugs with similar CNS actions, such as the barbiturates, share a common mechanism of action with the benzodiazepines? The development of biochemical techniques for identifying and characterizing CNS benzodiazepine receptors by radioligand binding in vitro and in vivo has been an important recent advance, although the benzodiazepine receptor remains in many ways an enigma. The hypothesis that the anticonvulsant actions of these drugs may be due to their ability to enhance the actions of GABA at CNS synapses is an attractive one, but many questions remain: Do all CNS benzodiazepine receptors interact with GABA sites, and are all GABA receptors linked to benzodiazepine sites? What is the endogenous ligand for the benzodiazepine receptors? Can the anxiolytic and sedative effects of the benzodiazepines be explained by their interaction with GABA mechanisms, or are other interactions more important? Is there more than one sub-type of benzodiazepine receptor in brain? Although these questions cannot be unequivocally answered, the benzodiazepines currently represent one of the most active and exciting areas for basic psychopharmacological research.