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• W2892382057 endingPage "878" @default.
• W2892382057 startingPage "836" @default.
• W2892382057 abstract "GABA_A receptors are the major inhibitory transmitter receptors in the brain. They are ligand-gated chloride channels and the site of action of benzodiazepines, barbiturates, neuroactive steroids, anesthetics, and convulsants. GABA_A receptors are composed of five subunits that can belong to different subunit classes. The existence of 19 homologous subunits and their distinct regional, cellular, and subcellular distribution gives rise to a large number of GABA_A receptor subtypes with distinct pharmacology, which modulate different functions of the brain. A variety of compounds have been identified that were claimed to modulate selectively individual GABA_A receptor subtypes. However, many of these compounds have only incompletely been investigated or, in addition to a preferential modulation of a receptor subtype, also modulate other subtypes at similar concentrations. Although their differential efficacy at distinct receptor subtypes reduced side effects in behavioral experiments in rodents, the exact receptor subtypes mediating their behavioral effects cannot be unequivocally delineated. In addition, the discrepant in vivo effects of some of these compounds in rodents and man raised doubts on the applicability of the concept of receptor subtype selectivity as a guide for the development of clinically useful drugs. Here, we provide an up-to-date review on the currently available GABA_A receptor subtype-selective ligands. We present data on their actual activity at GABA_A receptor subtypes, discuss the translational aspect of subtype-selective drugs, and make proposals for the future development of ligands with better anxioselectivity in humans. Finally, we discuss possible ways to strengthen the conclusions of behavioral studies with the currently available drugs." @default.
• W2892382057 created "2018-10-05" @default.
• W2892382057 creator A5078756600 @default.
• W2892382057 creator A5089382389 @default.
• W2892382057 date "2018-10-01" @default.
• W2892382057 modified "2023-10-10" @default.
• W2892382057 title "International Union of Basic and Clinical Pharmacology. CVI: GABA_A Receptor Subtype- and Function-selective Ligands: Key Issues in Translation to Humans" @default.
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