Document Detail

Therapeutic doses of theophylline exert proconvulsant effects in developing mice.
MedLine Citation:
PMID:  9339868     Owner:  NLM     Status:  MEDLINE    
We studied the effect of therapeutic doses of theophylline on electrically-induced convulsions in developing mice. A theophylline dose as small as 3 mg/kg increased seizure susceptibility of 21-day-old mice, but not of 42-day-old mice. These findings were consistent with clinical reports that theophylline at the therapeutic blood concentrations occasionally induced convulsions in children. The age-dependent proconvulsant effect of theophylline was well inhibited by phenobarbital (PB), dose-dependently, but not by other well-established antiepileptic drugs (AEDs). PB may be a good choice of AED in patients with bronchial asthma and seizure disorders, if PB is indicative for their seizure types. The proconvulsant effect of theophylline in 21-day-old mice was counteracted by not only an adenosine A1 agonist, but also an NMDA antagonist and a histamine H3 antagonist. Several studies have established that the proconvulsant effect of theophylline intoxication is mainly due to the blockade of adenosine A1 receptors. The present findings suggested that the proconvulsant properties of therapeutic doses of theophylline in developing period were different from those of theophylline intoxication. Combination of therapeutic doses of theophylline and centrally-acting histamine H1 antagonists showed proconvulsant effects even in 42-day-old mice, suggesting that peripherally acting histamine H1 antagonists, such as astemizole, evastine and epinastine, were much safer than centrally acting histamine H1 antagonists for patients with both allergy and seizure history.
H Yokoyama; K Onodera; T Yagi; K Iinuma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain & development     Volume:  19     ISSN:  0387-7604     ISO Abbreviation:  Brain Dev.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-11-26     Completed Date:  1997-11-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7909235     Medline TA:  Brain Dev     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  403-7     Citation Subset:  IM    
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
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MeSH Terms
Aging / physiology
Anticonvulsants / pharmacology
Bronchodilator Agents / administration & dosage,  blood,  toxicity*
Dose-Response Relationship, Drug
Histamine H1 Antagonists / administration & dosage,  toxicity
Mice, Inbred Strains
Phenobarbital / pharmacology
Seizures / chemically induced*
Theophylline / administration & dosage,  blood,  toxicity*
Reg. No./Substance:
0/Anticonvulsants; 0/Bronchodilator Agents; 0/Histamine H1 Antagonists; 50-06-6/Phenobarbital; 58-55-9/Theophylline

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

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