Related Experiment Videos
Aminophylline for methotrexate-induced neurotoxicity
J C Bernini1, D W Fort, J C Griener
1Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, USA.
Lancet (London, England)
|March 4, 1995
Summary
Methotrexate treatment for childhood leukemia can cause neurotoxicity. This study suggests adenosine release in the central nervous system mediates this toxicity and aminophylline may relieve symptoms.
Area of Science:
- Pediatric Oncology
- Neuroscience
- Pharmacology
Background:
- Methotrexate is a critical treatment for acute lymphoblastic leukemia in children.
- Methotrexate-induced neurotoxicity presents with symptoms like paralysis, seizures, and headaches, with unknown pathophysiology.
- Adenosine, a central nervous system depressant, is implicated in methotrexate's anti-inflammatory effects via purine synthesis inhibition.
Purpose of the Study:
- To investigate if central nervous system adenosine release contributes to methotrexate neurotoxicity in children.
- To determine if aminophylline can alleviate methotrexate-induced neurotoxicity by displacing adenosine from its receptors.
Main Methods:
- Administered aminophylline (2.5 mg/kg) to 6 children with methotrexate-induced neurotoxicity unresponsive to standard treatments.
- Measured cerebrospinal fluid (CSF) adenosine concentrations in children receiving methotrexate, newly diagnosed patients, and untreated controls.
Main Results:
- Complete resolution of neurotoxicity occurred in 4 of 6 patients treated with aminophylline; 2 others showed significant improvement.
- CSF adenosine levels were significantly elevated in children receiving methotrexate compared to control groups (mean 217 vs. 51 nmol/L).
Conclusions:
- Subacute methotrexate neurotoxicity in children may be mediated by elevated adenosine levels in the central nervous system.
- Aminophylline shows potential as an effective treatment for relieving methotrexate-induced neurotoxicity.