The glycine site of NMDA receptors: A target for cognitive enhancement in psychiatric disorders

Publication date: Available online 6 February 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Bahareh Peyrovian, Joshua D. Rosenblat, Zihang Pan, Michelle Iacobucci, Elisa Brietzke, Roger S. McIntyreAbstractCognitive dysfunction is a principal determinant of functional impairment in major depressive disorder (MDD) and often persists during periods of euthymia. Abnormalities in the glutamate system, particularly in N-methyl-d-aspartate receptors (NMDARs) activity, have been shown to contribute to both mood and cognitive symptoms in MDD. The current narrative review aims to evaluate the potential pro-cognitive effects of targeting the glycine site of NMDARs in the treatment of psychiatric disorders, with a special focus on how these results may apply to MDD. Literature databases were searched from inception to May 2018 for relevant pre-clinical and clinical studies evaluating antidepressant and pro-cognitive effects of NMDAR glycine site modulators in both MDD and non-MDD samples. Six glycine site modulators with pro-cognitive and antidepressant properties were identified: d-serine (co-agonist), d-cycloserine (partial agonist), d-alanine (co-agonist), glycine (agonist), sarcosine (co-agonist) and rapastinel (partial agonist). Preclinical animal studies demonstrated improved neuroplasticity and pro-cognitive effects with these agents. Numerous proof-of-concept clinical trials demonstrated pro-cognitive and antidepressant effects trans-diagnos...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research