TY - JOUR
T1 - Nmda antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia
AU - Olney, John W.
AU - Farber, Nuri B.
N1 - Funding Information:
This work was supported in part hy an NIMH Research Scientist Award MH 33894 (JWO), DA 06454, DA 05072, DA 07261, AG 05681, a research award from the Scuttish Rite Benevolent Foundation’s Schizophrenia Research Program to NBF. and an Established Investigator Award to JWO from NARSAD.
PY - 1995/12
Y1 - 1995/12
N2 - 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).
AB - 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).
KW - Addiction
KW - Emergence reactions
KW - NMDA antagonist neurotoxicity
KW - Pain
KW - Posterior cingulate and retrosplenial cortices
KW - Psychosis
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=0029592136&partnerID=8YFLogxK
U2 - 10.1016/0893-133X(95)00079-S
DO - 10.1016/0893-133X(95)00079-S
M3 - Review article
C2 - 8747758
AN - SCOPUS:0029592136
SN - 0893-133X
VL - 13
SP - 335
EP - 345
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 4
ER -