Antiepileptic drugs abolish ictal but not interictal epileptiform discharges in vitro.
OBJECTIVE
We established the effects of the antiepileptic drugs (AEDs) carbamazepine (CBZ), topiramate (TPM), and valproic acid (VPA) on the epileptiform activity induced by 4-aminopyridine (4AP) in the rat entorhinal cortex (EC) in an in vitro brain slice preparation.


METHODS
Brain slices were obtained from Sprague-Dawley rats (200-250 g). Field and intracellular recordings were made from the EC during bath application of 4AP (50 microm). AEDs, and in some experiments, picrotoxin were bath applied concomitantly.


RESULTS
Prolonged (>3 s), ictal-like epileptiform events were abolished by CBZ (50 microm), TPM (50 microm), and VPA (1 mm), whereas shorter (<3 s) interictal-like discharges continued to occur, even at concentrations up to 4-fold as high. gamma-Aminobutyric acid (GABA)(A)-receptor antagonism changed the 4AP-induced activity into recurrent interictal-like events that were not affected by CBZ or TPM, even at the highest concentrations. To establish whether these findings reflected the temporal features of the epileptiform discharges, we tested CBZ and TPM on 4AP-induced epileptiform activity driven by stimuli delivered at 100-, 10-, and 5-s intervals; these AEDs reduced ictal-like responses to stimuli at 100-s intervals at nearly therapeutic concentrations, but did not influence shorter interictal-like events elicited by stimuli delivered every 10 or 5 s.


CONCLUSIONS
We conclude that the AED ability to control epileptiform synchronization in vitro depends mainly on activity-dependent characteristics such as discharge duration. Our data are in keeping with clinical evidence indicating that interictal activity is unaffected by AED levels that are effective to stop seizures.
D'Antuono
Margherita
M
Montreal Neurological Institute and Department of Neurology, McGill University, Montreal, Quebec, Canada.
Köhling
Rüdiger
R
Ricalzone
Serena
S
Gotman
Jean
J
Biagini
Giuseppe
G
Avoli
Massimo
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002220:Carbamazepine / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D005632:Fructose / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology* / Q000517:prevention & control*; D000077236:Topiramate; D014635:Valproic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology
D015761:4-Aminopyridine; D000927:Anticonvulsants; D002220:Carbamazepine; D003292:Convulsants; D005632:Fructose; D010852:Picrotoxin; D011963:Receptors, GABA-A; D000077236:Topiramate; D014635:Valproic Acid
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