Consequences of benzodiazepine receptor occupancy.

The pharmacological consequences of the occupancy of benzodiazepine receptors have been a recent area of active research. There is good agreement between the electrophysiological effects of benzodiazepines and their binding to benzodiazepine receptors when both are studied in vitro under identical conditions. Compounds of different structure from the benzodiazepines can occupy the receptor in a way, which produces little overt effect (imidazodiazepines) or actually causes actions opposite to the benzodiazepines (beta-carbolines, inverse agonists). Several biochemical tests (GABA-shift, photo-shift) for distinguishing these different behavioral properties are described. A model is described for the interactions at membranes of agonists, antagonists and inverse agonists with benzodiazepine receptors in the GABA receptor complex.