Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus-like activity induced by low magnesium in rat entorhinal slices, but can prevent its development.
It was shown previously that low-Mg2+-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 microM, n=6), phenobarbital (150 microM, n=7), and midazolam (50 microM, n=5) were able to block the early SLEs but not the late activity at the same concentrations. Carbamazepine (50 microM) 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+]o 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 microM, n=5), carbamazepine (10 microM, n =6), and phenobarbital (50 microM, n = 4) had no effect. In conclusion, the hypothesis is supported that low-Mg2+-induced epileptiform activity in rat entorhinal cortex is an in vitro model for the transition from pharmacosensitive to pharmacoresistant status epilepticus.
Dreier
J P
JP
Department of Neurology, Charité, Humboldt-University, Berlin, Germany.
Zhang
C L
CL
Heinemann
U
U
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004569:Electroencephalography / Q000187:drug effects; D018728:Entorhinal Cortex / Q000187:drug effects* / Q000503:physiopathology; D008274:Magnesium / Q000502:physiology*; D008874:Midazolam / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000503:physiopathology*
D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin; D008274:Magnesium; D008874:Midazolam; D010634:Phenobarbital