The anticonvulsant action of AHR-11748 on kindled amygdaloid seizures in rats

Timothy E Albertson, William F. Walby

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The anticonvulsant effectiveness of AHR-11748 (3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) was evaluated in the kindled amygdaloid seizure model in rats. Doses of AHR-11748 that did not cause prestimulation toxicity significantly attenuated elicited afterdischarge durations and the severity of the accompanying behavioral convulsive response in previously kindled rats. AHR-11748 (25-100 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 μA increments) and suprathreshold (400 μA) paradigms. AHR-11748 (50-100 mg/kg) reduced suprathreshold elicited afterdischarges and seizure severity. Utilizing a suprathreshold kindling paradigm, the maximum anticonvulsant effectiveness for the 100 mg/kg i.p. dose of AHR-11748 was seen at 180 min. AHR-11748 significantly elevated seizure thresholds only at the 100 mg/kg dose. AHR-11748 (25-100 mg/kg) significantly reduced the severity of threshold elicited seizures. When AHR-11748 (50 and 100 mg/kg i.p.) was administered daily during kindling acquisition, the number of daily trials necessary to complete kindling significantly increased. A reduction in both the duration and the severity of the responses induced by the daily stimulations during the acquisition period was seen with AHR-11748 treatment. This study has demonstrated that AHR-11748 significantly modifies both the acquisition of kindling and the fully kindled amygdaloid seizures at doses that do not cause behavioral toxicity.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalEpilepsy Research
Volume1
Issue number2
DOIs
StatePublished - 1987

Keywords

  • AHR-11748
  • Anticonvulsants
  • Experimental epilepsy
  • Kindling
  • Seizure threshold

ASJC Scopus subject areas

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

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