Central-type and peripheral-type benzodiazepine receptors.

Abstract

The benzodiazepines had already been in wide use as anxiolytics and anticonvulsants for more than ten years before their site of action in the central nervous system, the benzodiazepine receptor, was discovered. Simultaneously, a binding site in the peripheral organs, e.g. heart, lungs and kidneys, was found. Although some benzodiazepines, such as diazepam, bind to both central and peripheral benzodiazepine receptors with a high affinity, these two binding sites exhibit quite different properties. It is already clear that the central benzodiazepine receptors are in many regions of the brain coupled with the receptors for gamma-amino butyric acid, and they mediate the acute actions of benzodiazepines in the central nervous system. Through them opposite effects, such as anxiety and convulsions, can also be evoked by using inverse agonists, e.g. some beta-carbolines. All these effects can be blocked with benzodiazepine receptor antagonists, some of which are already used as specific antidotes against benzodiazepine overdose. The multitude of pharmacological effects that can be produced through central benzodiazepine receptors provides a good opportunity for the development of new drugs. The role of the peripheral-type receptors is less clear, but it seems that they are connected with more slowly-appearing drug actions, such as modulation of cell proliferation. Now that endogenous ligands for both the central-type (a peptide called diazepam binding inhibitor; DBI) and for the peripheral-type (porphyrins) benzodiazepine receptors have been discovered, even more productive research can be expected.