Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.

ABSTRACT: Ionotropic glycine receptors (GlyRs) are chloride-permeable ligand-gated ion channels expressed in the nervous system. Alterations to glycinergic inhibition and the generation of dysfunctional GlyRs have been linked to chronic pain, a widely prevalent disease. Positive allosteric modulators (PAMs) targeting GlyRs exerted analgesic effects, motivating research on glycinergic PAMs as potential pain therapies. Rationally designed tricyclic sulfonamides are novel glycinergic PAMs with analgesic activity. However, detailed electrophysiological studies on these PAMs are still limited, and the GlyR binding site structural data has not been yet validated by mutational studies. Here, we combined electrophysiology and bioinformatics to systematically study the AM-1488 actions, a prototypical tricycl

SUBMITTER: Lara CO 

PROVIDER: S-EPMC11828983 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature