Twenty-five Years of Glutamate in Schizophrenia: Are We There Yet?
Year: 2012
Type: article
Abstract: At present, all medications for schizophrenia function primarily by blocking dopamine D2 receptors. Over 50 years ago, the first observations were made that subsequently led to development of alternative, glutamatergic conceptualizations. This special issue traces the historic development of the phencyclidine (PCP) model of schizophrenia from the initial description of the psychotomimetic effects of PCP in the early 1960s, through discovery of the link to N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the 1980s, and finally to the development of NMDA-based treatment strategies starting in the 1990s. NMDAR antagonists uniquely reproduce both positive and negative symptoms of schizophrenia, and induce schizophrenia-like cognitive deficits and neurophysiological dysfunction. At present, there remain several hypotheses concerning mechanisms by which NMDAR dysfunction leads to symptoms/deficits, and several theories regarding ideal NMDAR-based treatment approaches as outlined in the issue. Several classes of agent, including metabotropic glutamate agonists, glycine transport inhibitors, and D-serine-based compounds are currently in late-stage clinical development and may provide long-sought treatments for persistent positive and negative symptoms and cognitive dysfunction in schizophrenia.
Source: Schizophrenia Bulletin
Author: D. C. Javitt
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1980628262