Peripheral-type benzodiazepine receptors: a second site of action for benzodiazepines

Abstract

Benzodiazepines are among the most widely used therapeutic drugs because of their sedative and anxiolytic effects mediated through modulation of GABAA receptors. Another recognition site for these drugs, termed the peripheral-type (or mitochondrial) benzodiazepine receptor, is much more prevalent throughout the body for which a physiologic and pharmacologic role has just been found. This drug receptor plays a central role in the regulation of steroidogenesis by mediating the rate-limiting step in this biosynthetic pathway, which is transport of cholesterol to inner mitochondrial membranes. Although once considered by many to be an insignificant drug-binding site because a specific function remained elusive for many years, peripheral-type benzodiazepine receptors are now viewed with renewed interest because certain benzodiazepines such as diazepam may exert secondary effects on steroid production under appropriate physiologic conditions. Elucidation of this receptorial role should initiate new studies to examine in more detail the pharmacologic profile of drugs that bind to these sites and provides a novel target for the treatment of certain types of endocrine disorders.