Chemotherapy

Review

Biochemical and Clinical Aspects of Methotrexate Neurotoxicity

Vezmar S.a · Becker A.a · Bode U.b · Jaehde U.a

Author affiliations

Departments of aClinical Pharmacy,Institute of Pharmacy and bPaediatric Haematology/Oncology, Children’s Hospital, University of Bonn, Bonn, Germany

Keywords: MethotrexateNeurotoxicityFolatesHomocysteineAdenosineBiopterinsExcitatory amino acidsCNSCancer

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Chemotherapy 2003;49:92–104
https://doi.org/10.1159/000069773

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Article / Publication Details

First-Page Preview
Abstract of Review

Received: August 05, 2002
Accepted: January 02, 2003
Published online: May 07, 2003
Issue release date: May 2003

Number of Print Pages: 13
Number of Figures: 3
Number of Tables: 3

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE

Abstract

Acute, subacute and chronic neurotoxicity have been observed after the administration of high-dose and/or intrathecal methotrexate (MTX). Acute toxicity is usually transient without permanent damage. Subacute and chronic toxicity are associated with changes in the brain and/or the spinal cord which may be progressive and even lead to coma and death in severe cases. It is believed that MTX can induce direct toxic effects to the CNS by damaging the neuronal tissue. Moreover, MTX interferes with the metabolic pathways of folates, excitatory amino acids, homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, adenosine and biopterins, inducing biochemical alterations which have been associated with neurotoxic symptoms. It has been suggested that acute toxicity is partly mediated by adenosine, whereas homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, excitatory amino acids and biopterins may play an important role in the development of subacute and chronic toxicity. A better understanding of the pathogenesis of MTX neurotoxicity would offer the possibility of developing new therapeutic strategies for its treatment or prevention.

© 2003 S. Karger AG, Basel



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Article / Publication Details

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Abstract of Review

Received: August 05, 2002
Accepted: January 02, 2003
Published online: May 07, 2003
Issue release date: May 2003

Number of Print Pages: 13
Number of Figures: 3
Number of Tables: 3

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE

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