Effect of lamotrigine on a novel model of epilepsy.
The effect of lamotrigine (LTG) on evoked and spontaneous seizure-like activity induced by veratridine, was investigated. Rat brain slices were examined using conventional electrophysiological intracellular techniques. Alteration of sodium channel function by veratridine (0.3 microM) induced spontaneous seizure-like activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of LTG (5-10 microM) inhibited both evoked and spontaneous bursting induced by veratridine. This inhibition was voltage-dependent indicating possible interaction between the drug and the inactivated state of sodium channels. There was an increase in the firing threshold of the bursting but no change in the resting membrane potential (RMP) and membrane input resistance. Results from this work suggest that the veratridine model of epilepsy is very sensitive to drugs which act on sodium channels. These data make the veratridine model a suitable tool for screening potential sodium channel-dependent antiepileptic drugs.
Otoom
S A
SA
Department of Pharmacology, University of Science and Technology, School of Medicine, Irbid, Jordan.
Nusier
M K
MK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000502:physiology; D004195:Disease Models, Animal; D000077213:Lamotrigine; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008867:Microtomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology
D000927:Anticonvulsants; D014227:Triazines; D014701:Veratridine; D000077213:Lamotrigine