The effects of LY-201116 [4-amino-N-(2,6-dimethylphenyl) benzamide] on the amygdala-kindled rat.
The effects of LY-201116, a 4-aminobenzamide, were examined in rats using the amygdala kindling model, both during acquisition of the kindled response and in fully kindled animals. Dose-response and time-response studies for efficacy and rotorod toxicity were completed following intraperitoneal injection of the drug. Afterdischarge duration, behavioral seizure response, kindled seizure threshold and EEG recordings were used to assess efficacy and toxicity of the drug. In the acquisition trial, the drug (7.5 mg/Kg) did not significantly alter the number of stimulations required to produce the first stage 5 kindled response nor did it modify afterdischarge durations. Doses of 11.25 and 15 mg/Kg suppressed afterdischarge and diminished behavioral responses significantly in fully kindled rats, but these doses were also neurotoxic as judged by rotorod performance. The non-selective anticonvulsant effect of 11.25 mg/Kg lasted at least 90 min. A dose of 15 mg/Kg raised kindled seizure threshold and diminished afterdischarge duration. Doses of 20, 30 and 40 mg/Kg produced spontaneous EEG spikes and seizures accompanied by behavioral convulsions. The drug thus exhibited non-selective anticonvulsant effects in fully kindled rats following doses of 11.25 or 15 mg/Kg, but exhibited proconvulsant activity following doses in the range of 20-40 mg/Kg.
Stark
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Department of Medical Pharmacology and Toxicology, School of Medicine, University of California, Davis 95616.
Albertson
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D000679:Amygdala / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012640:Seizures / Q000503:physiopathology; D013997:Time Factors
D000927:Anticonvulsants; D001549:Benzamides; C055323:ameltolide