Effects of felbamate, kynurenic acid derivatives and NMDA antagonists on in vitro kainate-induced epileptiform activity.
The effects of the novel anticonvulsant felbamate, which binds to the 5-7 dichlorokynurenic binding sites, were tested towards the CA1 epileptiform activity induced in rat hippocampal slices by kainic acid. The effects of the kynurenic acid derivatives 7-chlorokynurenic acid and 5-7 dichlorokynurenic acid and of the NMDA antagonists CGS 19755, MK-801 and ketamine were also studied for comparison. Slice perfusion with 1 microM kainic acid produced within 30 min the development of an evoked CA1 epileptiform bursting made up by an increase in amplitude of the primary population spikes followed by the appearance of secondary epileptiform population spikes. Slice perfusion with CGS 19755 (100 microM) or MK-801 (100 microM) or ketamine (100 microM) failed to affect within 30 min the CA1 epileptiform activity due to kainic acid. On the contrary, slice perfusion with felbamate (1.3-1.6 mM) or 7-chlorokynurenic acid (100 microM) or 5-7-dichlorokynurenic acid (100 microM) produced within 30 min a significative (p < 0.05) decrease of the kainate-induced epileptiform bursting duration. The results indicate that felbamate and kynurenic acid derivatives but not NMDA antagonists present an inhibitory effect against the epileptiform activity due to kainic acid.
Domenici
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MR
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Marinelli
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S
Sagratella
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S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000078328:Felbamate; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D011409:Propylene Glycols; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D007608:Kainic Acid; C066192:5,7-dichlorokynurenic acid; D000078328:Felbamate