Recent advances in the GABA-A-benzodiazepine receptor pharmacology

Gamma-aminobutyric acid (GABA) acts on pharmacologically and functionally distinct receptors. These sites designated GABA-A and GABA-B receptors, differ with regard to their ionic characteristic and pharmacological properties. The most important distinction is, that the GABA-A receptor is associated with chloride channel and with membrane recognition sites for benzodiazepines. During the past decade numerous studies have made it possible to obtain more detailed knowledge of the structure and properties of the GABA-benzodiazepine receptor complex, which is made up of at least two distinct sites designated as BZD-1 and BZD-2 receptors. Third type, designated as peripheral type is located in the mitochondrial membrane and may regulate a steroidogenesis in the CNS. Molecular cloning studies showed a heterogeneity of GABA-A receptors, which are composed of multiple subunits (alpha, beta, gamma, delta and ro), which form distinct isoreceptors. New classes of GABA-BZD agonists such as zolpidem act selectively upon certain isoreceptors thus showing characteristic pharmacological properties. Recent studies provided detailed information on the interaction of ethyl alcohol (Et-OH) with GABA-BZD receptor complex. The most important finding is, that there are Et-OH sensitive and Et-OH resistant GABA-A receptor isoforms. Recent evidence reinforces the possibility, that reduced activity of the brain GABA-ergic system is associated with mechanism of depression.