GABA, receptor GABAA/benzodiazepine complex

GABAa receptors are pentameric complexes on the postsynaptic membrane with a central pore with selectivity for chloride ions. Benzodiazepines and barbiturates increase the GABA-induced chloride currents, leading to hyperpolarization of the postsynaptic membrane. 

Figure 6.1 GABAA-benzodiazepine receptor complex showing subunits and binding sites of ligands (binding sites for GABA and BDZ shown O).

The GABA-gated chloride ion channel is modulated by several classes of drugs that bind to allosteric sites on the receptor complex the benzodiazepines, barbiturates and related intravenous general anesthetics such as etomidate and propofol, as well as anesthetic steroids and endogenous neurosteroids. It appears that some types of GABAa receptor are directly enhanced by ethanol and volatile general anesthetics (Fig. 16-2) [7,8,20]. 

Zaleplon has a pharmacological profile similar to benzodiazepines. Zaleplon is a full agonist for the benzodiazepine oq receptor located on the GABAa receptor ionophore complex in the brain, with lower affinity for the a2 and a3 subtypes. It selectively enhances the action of GABA similar to but more selectively than benzodiazepines. Zaleplon, although not benzodiazepine-like in chemical structure, induces sedative-hypnotic, anticonvulsant, and anticonflict effects via its binding to the central nervous system (CNS)-type benzodiazepine receptors [33-36]. 

Figure 11.7 Schematic three-dimensional representation of the GABAa receptor complex with the recognition sites for GABA, benzodiazepines, alcohol, steroids, and barbiturates.

I The rrtajor psychopharmacological irrterest in GABA is the role of the GABAa receptor complex in ie action of benzodiazepines, barbiturates, alcohol and neurosteroids (Fig. 

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