Topiramate potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice

Giovambattista De Sarro, Santo Gratteri, Federico Bonacci, Sebastiano A. Musumeci, Maurizio Elia, Angela De Sarro

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
JournalEuropean Journal of Pharmacology
Volume388
Issue number2
DOIs
Publication statusPublished - Jan 28 2000

Fingerprint

Inbred DBA Mouse
Anticonvulsants
felbamate
Carbamazepine
Valproic Acid
Phenytoin
Phenobarbital
Diazepam
Seizures
topiramate
Drug Combinations
Pharmacokinetics

Keywords

  • Anticonvulsant
  • Audiogenic seizure
  • Carbamazepine
  • DBA/2 mouse
  • Epilepsy
  • Felbamate
  • Phenytoin
  • Topiramate
  • Valproate

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Topiramate potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice. / De Sarro, Giovambattista; Gratteri, Santo; Bonacci, Federico; Musumeci, Sebastiano A.; Elia, Maurizio; De Sarro, Angela.

In: European Journal of Pharmacology, Vol. 388, No. 2, 28.01.2000, p. 163-170.

Research output: Contribution to journalArticle

De Sarro, Giovambattista ; Gratteri, Santo ; Bonacci, Federico ; Musumeci, Sebastiano A. ; Elia, Maurizio ; De Sarro, Angela. / Topiramate potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice. In: European Journal of Pharmacology. 2000 ; Vol. 388, No. 2. pp. 163-170.
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