Pharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy

doi:10.1016/0920-1211(93)90058-F

Epilepsy Research

Volume 15, Issue 3, July 1993, Pages 207-219

https://doi.org/10.1016/0920-1211(93)90058-F Get rights and content

Abstract

By repeated treatment with phenytoin, subgroups of animals with different response to phenytoin were selected from a large group of amygdala-kindled rats. In one subgroup (‘phenytoin responders’) phenytoin induced reproducible increases in focal seizure threshold, while in another subgroup (‘phenytoin nonresponders’) animals were resistant to phenytoin. These phenytoin nonresponders, which comprised about 12% of the kindled animals tested, did not differ from phenytoin responders in drug levels, drug adverse effects or location of the stimulation electrode in the amygdala. Treatment of phenytoin responders and nonresponders with other primary antiepileptic drugs showed that valproate and phenobarbital induced much smaller increases in focal seizure threshold in phenytoin nonresponders than in responders, whereas carbamazepine induced about the same threshold increase in both groups. The novel antiepileptic drug vigabatrin, which acts by increasing GABA levels, exerted anticonvulsant effects in phenytoin responders but was inactive in nonresponders. Determination of plasma amino acids before and after vigabatrin treatment demonstrated marked differences in biochemical responses to vigabatrin although drug levels were about the same in both groups. The data demonstrate that amygdalakindled rats with phenytoin resistance offer a basic approach to the investigation of mechanisms of drug resistance in epilepsy. Furthermore, these animals may be used in the evaluation of new anticonvulsant drugs for treatment of partial seizures which do not respond to the currently available therapies.

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Research reportPharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy

Abstract

Development of a new pharmacological seizure model: effects of anticonvulsants on cortical- and amygdala-kindled seizures in the rat

Epilepsia

Pentylenetetrazole (PTZ) kindling in diazepam-sensitive and -resistant mice

Soc. Neurosci. Abstr.

Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans

Epilepsia

The relationship between GABA concentrations in brain and cerebrospinal fluid

Brain Res.

Intractable epilepsy: Introduction

The effect of interstimulation interval on the assessment and stability of kindled seizure threshold

Brain Res. Bull.

Anti-convulsant effect of primidone in the gerbil. Time course and significance of the active metabolites

Pharmacology

Mouse lines selected for genetic differences in diazepam sensitivity

Psychopharmacology

Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control

Drugs

Administration of vigabatrin (γ-vinyl-γ-aminobutyric acid) affects the levels of both inhibitory and excitatory amino acids in rat cerebrospinal fluid

J. Neurochem.

Effects of vigabatrin (γ-vinyl GABA) on neurotransmission-related amino acids and on GABA and benzodiazepine receptor binding in rats

Epilepsia

Do we need novel anti-epileptic drugs?

Br. J. Clin. Pract.

GABA in plasma and cerebrospinal fluid of different species. Effects of γ-acetylenic GABA, γ-vinyl GABA and sodium valproate

J. Neurochem.

Experimental models for intractable epilepsy in nonprimate animal species

Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA

Epilepsy Res.

The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models

Epilepsy Res.

Valproic acid in amygdala-kindled rats: Alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment

J. Pharmacol. Exp. Ther.

Consecutive gas Chromatographic determination of phenytoin, phenobarbital, primidone, phenylethylmalondiamide, carbamazepine, trimethadione, dimethadione, ethosuximide, and valproate from the same serum specimen

Epilepsia

Plasma GABA and seizure control with vigabatrin

Lancet

Research report
Pharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy