Biomarker-Based Pharmacological Characterization of ENX-102, a Novel α2/3/5 Subtype-Selective GABAA Receptor Positive Allo-Steric Modulator: Translational Insights from Rodent and Human Studies.

ABSTRACT: Gamma-aminobutyric acid type A receptors (GABA_ARs) are pentameric ligand-gated ion channels essential for inhibitory neurotransmission in the central nervous system. Subtype-specific expression patterns of GABA_AR subunits underlie their diverse roles in regulating anxiety, motor function, and sedation. While non-selective GABA_AR positive allosteric modulators (PAMs), such as benzodiazepines, are clinically effective anxiolytic drugs, their non-selective activity across α1/2/3/5 subunit-containing GABA_ARs leads to sedation, cognitive impairment, and risk of dependence. To address this, we evaluated ENX-102, a novel GABA_AR PAM, which exhibits selectivity for α2/3/5 subunits. In rodents, ENX-102 demonstrated dose-dependent anxiolytic-like

SUBMITTER: Nettesheim P 

PROVIDER: S-EPMC12564412 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature