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
Related Articles
- EP ID EP144486
- DOI -
- Views 106
- Downloads 0
Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes.
The main objective of the study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60 g) were randomly divided into six groups, namely: Norma...
Is the mGlu5 receptor a possible target for new antidepressant drugs?
The current treatment of depression, based on conventional antidepressant drugs that influence monoaminergic systems, is not satisfactory, and innovative antidepressant drugs are still needed. The next generation of trea...
Changes in the Egr1 and Arc expression in brain structures of pentylenetetrazole-kindled rats.
Background: Epileptogenesis is regarded as a complicated and relatively poorly understood phenomenon. Some of immediate early genes (IEGs) as egr1 (zif268) or arc (arg3.1) are believed to play an important role in the pr...
Drug therapy in autism: a present and future perspective.
Autism is a neurodevelopmental disorder, with a multifactorial etiology, characterized by severe abnormalities in communications, social awareness and skills, and the presence of restrictive and stereotyped patterns of b...
Baclofen influences acquisition and MMP-2, MMP-9 levels in the hippocampus of rats after hypoxia.
Background: Baclofen, the agonist of GABA(B) receptors, influences hypoxia-induced deficits in learning and memory processes. Methods: We studied the effects of baclofen on acquisition in the passive avoidance test and i...