Many drugs that target and co-activate glutamatergic pathways have been of interest as a non-dopaminergic approach to improve antipsychotic treatment in schizophrenia. Strategies to improve glutamate NMDA receptor hypoactivity on GABAergic interneurons have targeted extracellular binding sites on the receptor. The glycine modulatory site has been investigated as a target to improve NMDA receptor hypofunction in schizophrenia and several agonists or partial agonists of this binding site on the NMDA receptor have been studied in clinical trials (138).