Glycinergic signaling in the human nervous system: An overview of therapeutic drug targets and clinical effects

Glycine and related endogenous compounds (d-serine, d-alanine, sarcosine) serve critical roles in both excitatory and inhibitory neurotransmission and are influenced by a multitude of enzymes and transporters, including glycine transporter 1 and 2 (GlyT1 and GlyT2), d-amino acid oxidase (DAAO), serine racemase (SRR), alanine-serine-cysteine transporter 1 (Asc-1), and kynurenine aminotransferase (KAT). MEDLINE, Web of Science, and PsychINFO were searched for relevant human trials of compounds. Many studies utilizing exogenous administration of small molecule agonists of the glycineB site of n-methyl-d-aspartate receptor have been studied as have a growing number of glycine transporter type 1 (GlyT1) inhibitors. The clinical effects of these compounds are reviewed as are the potential effects of newer novel compounds.