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Science 11 August 1989:
Vol. 245. no. 4918, pp. 648 - 651
DOI: 10.1126/science.2569762
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Articles

Science, Vol 245, Issue 4918, 648-651
Copyright © 1989 by American Association for the Advancement of Science

articles

NMDA antagonists differentiate epileptogenesis from seizure expression in an in vitro model

SF Stasheff, WW Anderson, S Clark, and WA Wilson

Epilepsy Center, Veterans Administration Medical Center, Durham, NC 27705.

In an electrographic model of seizures in the hippocampal slice, both of the N-methyl-D-aspartate (NMDA) antagonists 2-amino-5-phosphonovaleric acid and 5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) prevented the progressive development of seizures but did not block previously induced seizures. Thus, a process dependent on the NMDA receptor-ionophore complex establishes a long-lasting, seizure-prone state; thereafter the seizures depend on non-NMDA receptor-ionophore mechanisms. This suggests that there is an important distinction between epileptogenesis and seizure expression and between antiepileptogenic and anticonvulsant pharmacological agents.


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