Acute high‐dose methotrexate neurotoxicity in the rat Journal Article

  


Authors: Phillips, P. C.; Thaler, H. T.; Berger, C. A.; Fleisher, M.; Wellner, D.; Allen, J. C.; Rottenberg, D. A.
Article Title: Acute high‐dose methotrexate neurotoxicity in the rat
Abstract: Intravenous high‐dose methotrexate chemotherapy may produce acute, subacute, or chronic neurotoxicity in patients with cancer. Acute encephalopathies following high‐dose methotrexate treatment are recognized with increasing frequency. This study describes a model of acute high‐dose methotrexate neurotoxicity in the rat characterized by a profound dose‐dependent depression of cerebral glucose metabolism in association with behavioral and electroencephalographc abnormalities. Alterations in the amino acid profile, similar to those described in cancer patients after high‐dose methotrexate treatment, were observed in the absence of biochemical evidence of systemic organ toxicity. This model facilitates the study of the biochemical mechanisms of antifolate neurotoxicity in humans and permits the evaluation of potential therapeutic interventions. Copyright © 1986 American Neurological Association
Keywords: unclassified drug; dose response; nonhuman; methotrexate; neurotoxicity; animal cell; cytology; animals; biological model; animal experiment; central nervous system; brain; diagnosis; drug response; rat; brain diseases; drug tissue level; glucose; rats; drug monitoring; drug metabolism; drug blood level; radioisotope; amino acids; drug determination; infusions, intravenous; electrocardiography; heart; model; autoradiography; intravenous drug administration; pharmacokinetics; electroencephalography; behavior, animal; nervous system; etiology; glucose metabolism; intoxication; deoxyglucose; rats, inbred strains; male; priority journal; article; deoxyglucose c 14; blood and hemopoietic system; drug analysis
Journal Title: Annals of Neurology
Volume: 20
Issue: 5
ISSN: 0364-5134
Publisher: Wiley Blackwell  
Date Published: 1986-11-01
Start Page: 583
End Page: 589
Language: English
DOI: 10.1002/ana.410200505
PUBMED: 3789673
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0023028399&doi=10.1002%2fana.410200505&partnerID=40&md5=b690d77138324c04b18b5ca71ecc0b9d
Notes: Article -- Export Date: 18 August 2021 -- Source: Scopus; Acknowledgments: The, arterial ammonia assay was performed by Dr Gordon F. Fairclough at the Laboratory of Clinical Biochemistry, New York Hospital. The authors wish to thank John Redd for skillful technical assistance and Adele Ahronheim for preparation of the manuscript.
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MSK Authors
  1. Martin Fleisher
    312 Fleisher
  2. Howard T Thaler
    245 Thaler
  3. David A. Rottenberg
    41 Rottenberg
  4. Jeffrey Allen
    22 Allen
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