The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats

Timothy E Albertson, William F. Walby

Research output: Contribution to journalArticlepeer-review

Abstract

The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 μA increments) and suprathreshold (400 μA) paradigms. Nafimidone (25-50 mg/kg) significantly reduced suprathreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity. The maximum anticonvulsant effectiveness for the 25 mg/kg i.p. dose of nafimidone was seen between 15 and 30 min utilizing a suprathreshold kindling paradigm. Nafimidone did not significantly elevate seizure thresholds at the doses tested; however, nafimidone (3.1-50 mg/kg) reduced the severity and afterdischarge duration of threshold elicited seizures in a non-dose response manner. Drug-induced electroencephalographic spikes were seen in both cortex and amygdala in most kindled rats receiving 100-120 mg/kg i.p. within 30 min of dosing before electrical stimulation. The frequency of spike and wave complexes increased in most of these animals leading to drug-induced spontaneous seizures and death in approximately 25% before electrical stimulation. This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy.

Original languageEnglish (US)
Pages (from-to)20-26
Number of pages7
JournalEpilepsy Research
Volume2
Issue number1
DOIs
StatePublished - 1988

Keywords

  • Anticonvulsants
  • Experimental epilepsy
  • Kindling
  • Nafimidone
  • Seizures threshold

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Neurology

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