PMID: 25751008Mar 10, 2015Paper

Selective Modulators of α5-Containing GABAA Receptors and their Therapeutic Significance

Current Drug Targets
Ming Shiuan Soh, Joseph W Lynch

Abstract

GABAA receptors containing the α5 subunit (5GABAARs) are found mainly in the hippocampus where they mediate a tonic chloride leak current and contribute a slow component to GABAergic inhibitory synaptic currents. Their inhibitory effect on the excitability of hippocampal neurons at least partly explains why changes in the level of activity of 5GABAARs affect cognition, learning and memory. These receptors have been implicated as potential therapeutic targets for a range of clinical conditions including age-related dementia, stroke, schizophrenia, Down syndrome and anesthetic- induced amnesia. Accordingly, a range of pharmacological modulators that selectively target 5GABAARs, as either inhibitors or allosteric enhancers, have been developed. Although many of these compounds show therapeutic effects in animal models of the above clinical disorders, none has been marketed yet due to unsuccessful clinical trials and toxicity in humans. These experiments have also revealed paradoxical effects of 5GABAAR modulation (e.g., cognitive impairments can be reversed by both positive and negative modulation), suggesting that our knowledge of the physiological roles of 5GABAARs is incomplete. This review highlights the various positive and n...Continue Reading

Citations

Jan 19, 2016·Frontiers in Molecular Neuroscience·Christine L DixonJoseph W Lynch
Jan 5, 2019·Journal of Molecular Neuroscience : MN·Fatin H Mohamad, Ahmad Tarmizi Che Has
Jun 16, 2018·Trends in Pharmacological Sciences·Elif EnginUwe Rudolph

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