GABAa receptors, activation subtypes

Neuro steroids, which may be physiological modulators of brain activity, enhance GABAa receptor function 297 The three-dimensional structures of ligand-gated ion channel receptors are being modeled successfully 297 Mouse genetics reveal important functions for GABAa receptor subtypes 297... 

The GABAA receptor is now believed to be the major target site for anaesthetic action. The GABAA receptors exist as a family of subtypes with their pharmacology determined by their composition. GABAA receptors are pentameric and comprise of two a, two 3 (or 0), and one y (or s) subunits, which assemble to form a chloride-sensitive pore. When the receptor is activated, transmembrane chloride conductance increases, resulting in hyperpolarisation of the postsynaptic cell membrane and functional inhibition of the postsynaptic neurone. 

Zolpidem (an imidazopyridine), zale-plone (a pyrazolopyrimidine) and zopi-clone (a cyclopyrrolone) are hypnotics that, despite their different chemical structure, can bind to the benzodiazepine site on the GABAa receptor (p. 222). However, their effects do not appear to be identical to those of benzodiazepines. Thus, compared with benzodiazepines, zolpidem exerts a weaker effect on sleep phases, supposedly carries a lower risk of dependence, and appears to have less anxiolytic activity. Heterogeneity of GABAa receptors may explain these differences in activity. GABAa receptors consist of five subunits that exist in several subtypes. 

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