Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neuropsychopharmacology. 1995 Dec;13(4):335-45.

NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia.

Author information

  • 1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Abstract

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate (Glu) receptor have become the focus of considerable attention as potential neurotherapeutic agents in view of mounting evidence implicating NMDA receptors in acute central nervous system (CNS) injury syndromes such as stroke, trauma, and status epilepticus. In addition, NMDA receptor antagonists are of potential interest for the clinical management of neuropathic pain and preventing the development of tolerance to opiate analgesics. A potentially serious obstacle to the development of NMDA antagonists as neurotherapeutic drugs is the paradoxical fact that whereas these agents do have significant neurotherapeutic potential, they also have psychotogenic and neurotoxic properties. We have been intensively investigating the mechanisms underlying these adverse properties and have discovered several methods of suppressing or preventing their expression. In addition, we have been exploring the possibility that a common mechanism may underlie the psychotogenic and neurotoxic actions of these agents and that this mechanism may have relevance to the pathogenesis of idiopathic psychotic processes such as schizophrenia. In this chapter, we will review our findings pertaining to NMDA antagonists in the dual context of their value as tools for exploring mechanisms underlying neuropsychiatric disturbances, particularly schizophrenia, and their potential promise as therapeutic agents. For additional references and a more complete elaboration of our hypothesis pertaining to NMDA receptor dysfunction and schizophrenia, please see a recent review (Olney and Farber 1995).

PMID:
8747758
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk