Format

Send to

Choose Destination
See comment in PubMed Commons below
Pol J Pharmacol. 2003 May-Jun;55(3):363-70.

Influence of vigabatrin, a novel antiepileptic drug, on the anticonvulsant activity of conventional antiepileptics in pentetrazole-induced seizures in mice.

Author information

1
Department of Pharmacology and Toxicology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland.

Abstract

Vigabatrin is a novel antiepileptic drug, which increases GABA levels by irreversible inhibition of GABA-aminotransferase. The aim of this study was to evaluate the effects of vigabatrin on the anticonvulsant activity of valproate, ethosuximide and clonazepam against pentetrazole-induced seizures in mice. In addition, the effects of antiepileptic drugs alone or in combination with vigabatrin were studied on motor performance and long-term memory. Chemical seizures were induced by subcutaneous injection of pentetrazole at its CD(97) and defined as a clonus of the whole body with an accompanying loss of righting reflex, lasting for over 3 s. Vigabatrin inhibited the clonic pentetrazole-induced seizures and ED(30) of the drug was 879 mg/kg. Vigabatrin (at the subthreshold dose of 250 mg/kg) potentiated the protective activity of ethosuximide, reducing its ED(30) from 142 to 95 mg/kg against clonic seizures induced by pentetrazole, but simultaneously elevated its plasma level. The protective activity of valproate and clonazepam remained almost unchanged. However, vigabatrin (250 mg/kg) decreased TD(30) (50% toxic dose - corresponding to the impairment of motor coordination in 50% of the animals) of ethosuximide and clonazepam from 549 and 3.84 to 460 and 1.1 mg/kg, respectively, in the chimney test. Vigabatrin (250 mg/kg) did not influence TD(30) value of valproate in this test. Vigabatrin (at the dose of 250 mg/kg) did not impair long-term memory in combination with antiepileptics. Potentiation of the ethosuximide's protective activity was apparently due to a pharmacokinetic interaction. Consequently, no pharmacodynamic interactions between vigabatrin and the studied conventional antiepileptic drugs were evident.

PMID:
14506315
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Institute of Pharmacology Polish Academy of Sciences
    Loading ...
    Support Center