Modulators of the Inhibitory Glycine Receptor.

The inhibitory glycine receptor is a member of the Cys-loop superfamily of ligand-gated ion channels. It is the principal mediator of rapid synaptic inhibition in the spinal cord and brainstem and plays an important role in the modulation of higher brain functions including vision, hearing, and pain signaling. Glycine receptor function is controlled by only a few agonists, while the number of antagonists and positive or biphasic modulators is steadily increasing. These modulators are important for the study of receptor activation and regulation and have found clinical interest as potential analgesics and anticonvulsants. High-resolution structures of the receptor have become available recently, adding to our understanding of structure-function relationships and revealing agonistic, inhibitory, and modulatory sites on the receptor protein. This Review presents an overview of compounds that activate, inhibit, or modulate glycine receptor function in vitro and in vivo.