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

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 microA increments) and suprathreshold (400 microA) paradigms. AHR-11748 (50-100.mg/kg) reduced suprathreshold elicited after discharges 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.

• Authors: T E Albertson, W F Walby
• Journal: Epilepsy research (Epilepsy Res) Vol. 1 Issue 2 Pg. 126-33 (Mar 1987) ISSN: 0920-1211 [Print] Netherlands
• PMID: 3504388 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants

Topics

• Amygdala (drug effects, physiopathology)
• Animals
• Anticonvulsants (pharmacology)
• Dose-Response Relationship, Drug
• Kindling, Neurologic (drug effects)
• Male
• Rats
• Rats, Inbred Strains