Enhanced glutamatergic transmission reduces the anticonvulsant potential of lamotrigine but not of felbamate against tonic-clonic seizures.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 4
Abstract
The efficacy of lamotrigine and felbamate against maximal electroshock (MES)-induced seizures was assessed under conditions mimicking the pharmacoresistance associated with an increased excitatory neurotransmission. N-methyl-D-aspartate (NMDA), but not kainate applied at subconvulsive dose, reduced the activity of lamotrigine against MES-induced seizures increasing its ED(50) value from 4.3 (3.2-5.6) to 6.1 (5.2-7.2) mg/kg (p < 0.001). This effect was reversed by co-application of an NMDAreceptor antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116) at 0.1 mg/kg [4.5 (3.7-5.6) vs. 6.1 (5.2-7.2) mg/kg; p < 0.001]. The anticonvulsive action of felbamate was altered by neither NMDAnor kainate. In conclusion, the data presented here indicate that felbamate, but not lamotrigine, effectively prevents generalized tonic-clonic seizures, also when NMDA-mediated neurotransmission is enhanced. The impaired antiepileptic potential of lamotrigine might be restored in such scenario by the co-administration of a very low dose of NMDA receptor antagonist.
Authors and Affiliations
Tomasz Tomczyk, Grzegorz Haberek, Beata Zuchora, Agata Jarosławska-Zych, Mieczysław Kowalczyk, Marian Wielosz, Ewa Urbańska
Keywords
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