Document Detail


Topiramate potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice.
MedLine Citation:
PMID:  10666508     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Topiramate (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in DBA/2 mice in a dose-dependent manner. Topiramate at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The degree of potentiation induced by topiramate was greatest for diazepam, phenobarbital and valproate, less for lamotrigine and phenytoin and not significant for carbamazepine and felbamate. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of the combination of all drugs+topiramate was more favourable than that of antiepileptics+ saline, with the exception of carbamazepine or felbamate+topiramate. Since topiramate did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that topiramate can modify the clearance from the brain of the anticonvulsant drugs studied cannot be excluded. In addition, topiramate did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, topiramate showed an additive effect when administered in combination with some classical anticonvulsants, most notably diazepam, phenobarbital, lamotrigine, phenytoin and valproate.
Authors:
G De Sarro; S Gratteri; F Bonacci; S A Musumeci; M Elia; A De Sarro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  388     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-03-16     Completed Date:  2000-03-16     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  163-70     Citation Subset:  IM    
Affiliation:
Chair of Pharmacology, Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, Policlinico Mater Domini, Via T. Campanella, 88100, Catanzaro, Italy. desarro@unicz.it
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MeSH Terms
Descriptor/Qualifier:
Acoustic Stimulation
Animals
Anticonvulsants / blood,  pharmacology*
Body Temperature / drug effects
Dose-Response Relationship, Drug
Drug Synergism
Female
Fructose / analogs & derivatives*,  pharmacology
Male
Mice
Mice, Inbred DBA
Motor Activity / drug effects
Postural Balance / drug effects
Seizures / prevention & control*
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0H73WJJ391/topiramate; 30237-26-4/Fructose

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


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