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 83
- Downloads 0
Experimental asthma in rats.
Animal models of asthma have been used for over 100 years. The accuracy of extrapolations from animal models to human asthmatics is highly dependent on the species of animal selected. The rat, in comparison with other an...
Effects of selective sigma receptor ligands on glucocorticoid receptor-mediated gene transcription in LMCAT cells.
It has been shown previously that sigma receptor agonists reveal potential antidepressant activity in experimental models. Moreover, some data indicate sigma receptor contribution to stress-induced responses (e.g., condi...
Influence of aripiprazole and olanzapine on behavioral dysfunctions of adolescent rats exposed to stress in perinatal period.
Background: Schizophrenia is a group of mental disorders of unclear origin, affecting around 1% of global population, most commonly young people. Of various treatment methods, pharmacotherapy using atypical neuroleptics...
Glyburide for the treatment of gestational diabetes mellitus.
Insulin is the traditional treatment for gestational diabetes mellitus (GDM) unresponsive to dietary interventions. Until recently, oral hypoglycemic drugs had been contraindicated due to concerns regarding teratogenicit...
Introduction to early in vitro identification of metabolites of new chemical entities in drug discovery and development.
The introduction of combinatorial chemistry and robotics for high throughput screening has changed the way drugs are discovered today compared with 10-15 years ago when fewer compounds were tested in animal or organ mode...