Document Detail

Antipsychotic medications, glutamate, and cell death: A hidden, but common medication side effect?
MedLine Citation:
PMID:  23265349     Owner:  NLM     Status:  Publisher    
We hypothesize the interaction between antipsychotic medications and regulation of extracellular glutamate which has gone largely unnoticed in the medical community has significant clinical importance. Typical antipsychotic medications such as haloperidol elevate extracellular glutamate because they exert antagonist effects on dopamine D(2) and serotonin 5HT(1A) receptors. In contrast, serotonin 5HT(2A) receptor antagonists inhibit glutamate release. Glutamate is potentially excitotoxic through effects on ionotropic receptor channels and may exert synergistic effects with other neurotoxic pathways. In contrast to typical antipsychotic drugs, pharmacological properties of atypical antipsychotic medications at dopamine D(2), serotonin 5HT(1A) and 5HT(2A) receptors limit extracellular glutamate and may theoretically be neuroprotective in certain clinical settings. In this review we discuss three common clinical settings in which typical antipsychotic medications may potentiate neurotoxicity by elevating extracellular glutamate. The most common clinical setting, hypoglycemia during combined use of antipsychotic medications and insulin, presents a theoretical risk for 35 million diabetic patients worldwide using antipsychotic medications. Antipsychotic medication treatment during hypoxic episodes in the intensive care unit and following traumatic brain injury are two other common clinical settings in which this interaction poses theoretical risk. Further study is needed to test hypothesized risk mechanisms, and determine clinical and epidemiological consequences of these exposures.
Amanda M Isom; Gary A Gudelsky; Stephen C Benoit; Neil M Richtand
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-19
Journal Detail:
Title:  Medical hypotheses     Volume:  -     ISSN:  1532-2777     ISO Abbreviation:  Med. Hypotheses     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, United States; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, United States. Electronic address:
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