A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate in neocortical slices.
We studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779 (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked field potentials recorded from rat prefrontal and frontal cortical slices. In the presence of physiologic concentrations of extracellular magnesium (1.2 mM) the field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When magnesium was removed from the bathing medium, there was a significant NMDA-mediated component of the field potential. LTG and GP 47779 decreased, in a dose-dependent manner, the field potential amplitude under both experimental conditions. FBM caused a dose-related decrease of the field potential amplitude only in the absence of external magnesium, suggesting a selective interaction with an NMDA-mediated component of this potential. These findings indicate that the reduction of cortical excitatory transmission might represent a common target for new antiepileptic drugs.
Calabresi
P
P
Clinica Neurologica, Università di Roma Tor Vergata, Italy.
Siniscalchi
A
A
Pisani
A
A
Stefani
A
A
Mercuri
N B
NB
Bernardi
G
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects*; D000078328:Felbamate; D000077213:Lamotrigine; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology*
C039775:10,11-dihydro-10-hydroxycarbamazepine; D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine; D000078328:Felbamate