Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid.
Methotrexate (MTX) is an antifolate that affects many metabolic pathways. MTX may cause neurologic toxicity, but the biochemical effects of MTX on the central nervous system (CNS) are poorly characterized. The authors studied serial cerebrospinal fluid (CSF) samples from a child during two courses of intraventricular MTX and found a rapid and reproducible depletion in CSF of reduced folates and S-adenosylmethionine that was accompanied by marked increases in homocysteine and adenosine. No sulfur-containing excitatory amino acids were detected. This study demonstrates multiple profound effects of MTX on CNS metabolism and provides insight to the pathogenesis of MTX neurotoxicity.
Quinn
Charles T
CT
Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, Texas 75390-9063, USA. Charles.Quinn@UTSouthwestern.edu
Griener
James C
JC
Bottiglieri
Teodoro
T
Arning
Erland
E
Winick
Naomi J
NJ
D000596:Amino Acids / Q000134:cerebrospinal fluid*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D002675:Child, Preschool; D004837:Epinephrine / Q000134:cerebrospinal fluid*; D005492:Folic Acid / Q000134:cerebrospinal fluid*; D006710:Homocysteine / Q000134:cerebrospinal fluid*; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D009367:Neoplasm Staging
D000596:Amino Acids; D000964:Antimetabolites, Antineoplastic; D006710:Homocysteine; D005492:Folic Acid; D004837:Epinephrine; D008727:Methotrexate