Document Detail

Methylxanthines, seizures, and excitotoxicity.
MedLine Citation:
PMID:  20859799     Owner:  NLM     Status:  MEDLINE    
Clinical evidence, in particular the wide use of theophylline as a bronchodilator, suggests that methylxanthines can cause seizures in patients without known underlying epilepsy. Theophylline is also known to be an added risk factor for seizure exacerbation in patients with epilepsy. The proconvulsant activity of methylxanthines can best be explained by their antagonizing the brain's own anticonvulsant adenosine. Recent evidence suggests that adenosine dysfunction is a pathological hallmark of epilepsy contributing to seizure generation and seizure spread. Conversely, adenosine augmentation therapies are effective in seizure suppression and prevention, whereas adenosine receptor antagonists such as methylxanthines generally exacerbate seizures. The impact of the methylxanthines caffeine and theophylline on seizures and excitotoxicity depends on timing, dose, and acute versus chronic use. New findings suggest a role of free radicals in theophylline-induced seizures, and adenosine-independent mechanisms for seizure generation have been proposed.
Detlev Boison
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review    
Journal Detail:
Title:  Handbook of experimental pharmacology     Volume:  -     ISSN:  0171-2004     ISO Abbreviation:  Handb Exp Pharmacol     Publication Date:  2011  
Date Detail:
Created Date:  2010-09-22     Completed Date:  2011-01-03     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7902231     Medline TA:  Handb Exp Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  251-66     Citation Subset:  IM    
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MeSH Terms
Adenosine / deficiency,  physiology
Caffeine / toxicity
Neurotoxins / toxicity*
Seizures / chemically induced*
Theophylline / toxicity
Xanthines / toxicity*
Grant Support
R01 MH083973/MH/NIMH NIH HHS; R01 MH083973-02/MH/NIMH NIH HHS; R01 NS058780/NS/NINDS NIH HHS; R01 NS058780-03/NS/NINDS NIH HHS; R01 NS061844/NS/NINDS NIH HHS; R01 NS061844-02/NS/NINDS NIH HHS; R01MH083973/MH/NIMH NIH HHS; R01NS058780/NS/NINDS NIH HHS; R01NS061844/NS/NINDS NIH HHS; R21 NS057475/NS/NINDS NIH HHS; R21 NS057475-02/NS/NINDS NIH HHS; R21 NS057538/NS/NINDS NIH HHS; R21 NS057538-02/NS/NINDS NIH HHS; R21NS057475-01/NS/NINDS NIH HHS; R21NS057538-01/NS/NINDS NIH HHS
Reg. No./Substance:
0/Neurotoxins; 0/Xanthines; 28109-92-4/methylxanthine; 3G6A5W338E/Caffeine; C137DTR5RG/Theophylline; K72T3FS567/Adenosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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