Pharmacological profiles in vivo of benzodiazepine receptor ligands

Abstract

Abstract Since the discovery of specific binding sites for benzodiazepines in the brain, a range of compounds have been discovered that do not have the benzodiazepine structure but that do interact with the benzodiazepine receptors. Classical benzodiazepines were considered to be agonists at these receptors. Some compounds only possess part of the profile of classical benzodiazepines and antagonise benzodiazepines in those test procedures in which they are totally inactive. Such compounds are regarded as partial agonists. The discovery of methyl and ethyl β‐carboline‐3‐carboxylate opened a new vista in the pharmacology of benzodiazepine receptors. These agents and now several other compounds act on the benzodiazepine receptors to induce effects functionally opposite to those of classical benzodiazepines (proconvulsant and convulsant) and have been called inverse agonists. Both agonists and inverse agonists can be blocked by compounds with affinity for the receptors but little intrinsic activity (antagonists). A recent increase in the number of benzodiazepine receptor ligands with in vivo activities allows comparison of a range of compounds from several different structral groups. Their pharmacological profiles suggest that these compounds all fit onto a continuum of behavioural effects related to activation of benzodiazepine receptors.