Targeting GABAergic Hypofunction Associated with Schizophrenia: Identification of α1β2γ2GABA-A Receptor Ligands with Neuroprotective and Antipsychotic Properties.

ABSTRACT: Clinical evidence has demonstrated significant hypofunction of GABAergic neurotransmission in patients with schizophrenia, likely contributing to the onset of psychotic symptoms. These symptoms can be alleviated by α1β2γ2GABA-A receptor ligands, which have previously shown antipsychotic activity. Building on this foundation, we synthesized and characterized various derivatives of 2-phenylimidazo[1,2-a]-pyridine containing cyclic amine moieties at the amide backbone to identify potent ligands and expand the chemical space of α1β2γ2GABA-A receptor ligands. The synthesized compounds exhibited K_i values ranging from 25.0 to 7822.5 nM and positive allosteric properties at α1β2γ2GABA-A receptors. Selected compounds exhibited promising cellular permeability properties, hi

SUBMITTER: Mordyl B 

PROVIDER: S-EPMC12186843 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature