Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety.

Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety. Acta Pharmacol Sin. 2018 Dec 05;: Authors: Chen X, van Gerven J, Cohen A, Jacobs G Abstract Anxiety disorders arise from disruptions among the highly interconnected circuits that normally serve to process the streams of potentially threatening stimuli. The resulting imbalance among these circuits can cause a fundamental misinterpretation of neural sensory information as threatening and can lead to the inappropriate emotional and behavioral responses observed in anxiety disorders. There is considerable preclinical evidence that the GABAergic system, in general, and its α2- and/or α5-subunit-containing GABA(A) receptor subtypes, in particular, are involved in the pathophysiology of anxiety disorders. However, the clinical efficacy of GABA-A α2-selective agonists for the treatment of anxiety disorders has not been unequivocally demonstrated. In this review, we present several human pharmacological studies that have been performed with the aim of identifying the pharmacologically active doses/exposure levels of several GABA-A subtype-selective novel compounds with potential anxiolytic effects. The pharmacological selectivity of novel α2-subtype-selective GABA(A) receptor partial agonists has been demonstrated by their distinct effect profiles on the neurophysiological and neuropsychological measurements that reflect the functions...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research