Is the glycine site half saturated or half unsaturated? Effects of glutamatergic drugs in schizophrenia patients.
OBJECTIVE
Current treatments for schizophrenia target the dopamine system. Developments of new treatments that target the glutamate system, however, are under progress, in particular, for the N-methyl-D-aspartate-type glutamate receptor. Compared with dopaminergic treatments, these treatments may show improved efficacy in the treatment of persistent negative symptoms.


RESULTS
During the past year, clinical trials have been published with several agonists at the glycine site of the N-methyl-D-aspartate receptor, including glycine, D-serine, D-alanine and with the glycine transport inhibitor, sarcosine. Studies published during the past year indicate highly significant beneficial effects on negative symptoms when these compounds are added to both conventional and newer atypical antipsychotics in efficacy models although an effectiveness trial of current formulations of glycine and D-cycloserine failed to show an overall benefit. Relevant issues across studies may include the compound chosen, its formulation and tolerability, populations studied, and the nature and dose of the base antipsychotic treatment.


CONCLUSIONS
The present findings continue to support the use of N-methyl-D-aspartate/glycine site agonists as potential new treatments for persistent negative symptoms of schizophrenia. Ongoing work with novel compounds and new formulations may assist in the translation of these advances into clinic-ready pharmacotherapies.
Javitt
Daniel C
DC
Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, New York 10962, USA. Javitt@nki.rfmh.org
D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use; D003523:Cycloserine / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism*; D012521:Sarcosine / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*
D000963:Antimetabolites; D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003523:Cycloserine; D003024:Clozapine; D005998:Glycine; D012521:Sarcosine