Preclinical pharmacology of alogabat: a novel GABA_A-α5 positive allosteric modulator targeting neurodevelopmental disorders with impaired GABA_A signaling.

ABSTRACT:

Background

Alterations in the GABAergic system contribute to the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD) and Angelman syndrome (AS), particularly in cases involving large deletions in the 15q11-13 region. Positive modulation of GABA_A-α5 receptors may provide a novel therapeutic approach without the typical side effects associated with non-selective GABA_A positive allosteric modulators such as diazepam.

Methods

Alogabat was assessed for binding and functional activity at GABA_A-α5β3γ2 receptors in vitro and in electrophysiological studies using hippocampal slices. In vivo studies in rodents included receptor occupancy (RO) using a selective GABA_A-α5 tracer (autoradiograp

SUBMITTER: Cecere G 

PROVIDER: S-EPMC12319775 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature