Benzodiazepine receptor ligands with positive and negative efficacy.

Recent studies have shown that benzodiazepine receptors can be affected not only by benzodiazepine agonists and antagonists but also by a new class of ligands which produce effects opposite to those of benzodiazepines, that is they produce convulsions and anxiety. These ligands can be described as having a negative efficacy at the receptor; tentatively they are named "inverse agonists". Pharmacological experiments indicate that agonists, antagonists and inverse agonists comprise a whole continuum of agents with a graduated variety of efficacy at the receptor. Biochemical studies, supported by published electrophysiological data, indicate that the benzodiazepine receptor allosterically up- or down-regulates the gain in the GABAergic system depending on the nature of the ligand.