Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus-like activity induced by low magnesium in rat entorhinal slices, but can prevent its development

Objectives - 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 mu M, n=6), phenobarbital (150 mu M, n=7), and midazolam (50 mu M, n=5) were able to block the early SLEs but not the late activity at the same concentrations. Carbamazepine (50 mu M) reduced the duration of the SLEs from 21+/-5 s to 4+/-3 s (P<0.01), the interictal interval from 123+/-7 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 mu M, n=5), carbamazepine (10 CIM, n=6), and phenobarbital (50 CIM, 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.