Source:http://linkedlifedata.com/resource/pubmed/id/13679230
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-9-18
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pubmed:abstractText |
Histamine is one of the aminergic neurotransmitters, playing an important role in the regulation of a number of physiological processes. There are several subtypes of histamine receptors-H(1), H(2), H(3) and the recently discovered H(4). H(1) receptors exist on mast cells, basophils, enterochromaffin cells and in the central nervous system, being located postsynaptically. H(1) receptor antagonists, including classical antiallergy drugs, occasionally have been expected to induce convulsions in children and epileptics. The aim of this study was to evaluate the effects of astemizole-given intraperitoneally, singly or for 7 days on the anticonvulsant activity of antiepileptic drugs (AEDs) against maximal electroshock (MES)-induced convulsions in mice. The following AEDs were administered intraperitoneally: valproate magnesium, carbamazepine, diphenylhydantoin and phenobarbital. Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Brain and plasma levels of AEDs were measured by immunofluorescence. Astemizole (a single dose and following a 7-day treatment at 2-6 mg/kg) reduced the threshold for electroconvulsions, being without effect upon this parameter at lower doses. Astemizole (1 mg/kg) did not significantly alter the protective effect of AEDs against MES (after acute and 7-day administration). Also, acute astemizole (2 mg/kg) remained ineffective in this respect. Astemizole (2 mg/kg), following chronic administration, significantly reduced the protective efficacy of phenobarbital and diphenylhydantoin, reflected by an increase in their ED(50) values (50% effective dose necessary to protect 50% of animals tested against MES) from 21.1 to 34.0 mg/kg and from 10.4 to 19.2 mg/kg, respectively. Astemizole (2 mg/kg) did not alter the protective activity of the remaining AEDs. Moreover, astemizole (2 mg/kg) did not influence the free plasma levels and brain concentration of the studied AEDs. Also, this H(1) receptor antagonist did not impair long-term memory or motor coordination when given acutely. However, 7-day treatment with astemizole (2 mg/kg) significantly decreased TD(50) (50% toxic dose required to induce motor impairment in 50% of animals) value of phenobarbital, being without effect on carbamazepine, valproate and diphenylhydantoin in this respect. Similarly, phenobarbital and diphenylhydantoin, administered alone at their ED(50)s against MES, or combined with astemizole, disturbed long-term memory in mice. The results of this study indicate that astemizole may need to be used with caution in epileptic patients.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0091-3057
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
76
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
169-78
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:13679230-Animals,
pubmed-meshheading:13679230-Anticonvulsants,
pubmed-meshheading:13679230-Astemizole,
pubmed-meshheading:13679230-Avoidance Learning,
pubmed-meshheading:13679230-Dose-Response Relationship, Drug,
pubmed-meshheading:13679230-Drug Interactions,
pubmed-meshheading:13679230-Histamine H1 Antagonists,
pubmed-meshheading:13679230-Male,
pubmed-meshheading:13679230-Mice,
pubmed-meshheading:13679230-Receptors, Histamine H1,
pubmed-meshheading:13679230-Seizures
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pubmed:year |
2003
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pubmed:articleTitle |
Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, Medical University, 20-090, Jaczewskiego 8, Lublin, Poland.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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