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Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus‐like activity induced by low magnesium in rat entorhinal slices, but can prevent its development
Author(s) -
Dreier J. P.,
Zhang C.L.,
Heinemann U.
Publication year - 1998
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1998.tb07286.x
Subject(s) - status epilepticus , phenobarbital , phenytoin , carbamazepine , anticonvulsant , midazolam , entorhinal cortex , ictal , chemistry , epilepsy , pharmacology , endocrinology , medicine , anesthesia , hippocampus , neuroscience , psychology , sedation
Objectives – It was shown previously that low‐Mg 2+ ‐induced epileptiform activity in rat entorhinal cortex slices changes with time from a pattern of serial seizure‐like events (SLEs) to a state of continuously recurring epileptiform activity. Valproic acid blocked the early SLEs but not the late activity. It was proposed that the late activity is a model for pharmacoresistant status epilepticus since it was also refractory to phenytoin, carbamazepine, phenobarbital, and midazolam. In the present study, it is demonstrated that phenytoin (50 μM, n =6), phenobarbital (150 μM, n =7), and midazolam (50 μM, n =5) were able to block the early SLEs but not the late activity at the same concentrations. Carbamazepine (50 μM) reduced the duration of the SLEs from 21±5 s to 4±3 s ( P <0.01), the interictal interval from 123±27 s to 27±19 s ( P <0.01), the SLE‐associated rise of [K + ] 0 from 7.7±0.5 mM to 5.7±0.8 mM ( n =4, P <0.05), and the spread of the SLE between entorhinal cortex and neocortex from 4.0±0.6 s to 0.8±0.1 s ( n =4, P <0.05). Lower concentrations of phenytoin (5 and 10 μM, n =5), carbamazepine (10 μM, n =6), and phenobarbital (50 μM, n =4) had no effect. In conclusion, the hypothesis is supported that low‐Mg 2+ ‐induced epileptiform activity in rat entorhinal cortex is an in vitro model for the transition from pharmacosensitive to pharmacoresistant status epilepticus.