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Current Topics in Pharmacology   Volumes    Volume 8  Issue 2
N-methyl-D-aspartate receptor modulation and schizophrenia
Hsien-Yuan Lane, Chieh-Liang Huang, Cher-Yeang Lin, Wen-Ho Chang
Pages: 305 - 312
Number of pages: 8
Current Topics in Pharmacology
Volume 8  Issue 2

Copyright © 2004 Research Trends. All rights reserved


Schizophrenia patients reveal positive symptoms, negative symptoms, and cognitive impairments. Among them, cognitive impairment, particularly attention deficit, is considered as one of schizophrenia endophenotypes. Atypical antipsychotics are beneficial to positive and negative symptoms as well as certain cognitive deficits. However, both risperidone (a commonly used atypical agent) and typical antipsychotics do not improve attentions in schizophrenia patients. Studies have showed that sub-anesthetic doses of ketamine (a NMDA antagonist) could produce positive symptoms, negative symptoms and attention deficits in healthy volunteers. Therefore, in addition to dopamine and serotonin theory, hypofunction of NMDA subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. Recently, D-serine (an endogenous, full agonist of the NMDA-glycine site) has been suggested to be a promising agent of enhancing NMDA function in schizophrenia patient. In a pilot study, D-serine was capable of improving treatment response in schizophrenia patients who were resistant to classical antipsychotics. However, the molecular mechanism of NMDA dysfunction of schizophrenia requires elucidation. Moreover, the efficacy (including cognitive effectiveness) and safety of D-serine plus atypical antipsychotics (or even D-serine monotherapy) in schizophrenia patients require further elucidation.

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