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 ED50 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / administration & dosage
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2-Amino-5-phosphonovalerate / analogs & derivatives
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Anticonvulsants / administration & dosage
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Anticonvulsants / pharmacology*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Electroshock / methods
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Felbamate
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Glutamic Acid / physiology*
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Injections, Intraperitoneal
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Kainic Acid / administration & dosage
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Kainic Acid / pharmacology
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Lamotrigine
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Male
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Mice
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N-Methylaspartate / administration & dosage
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N-Methylaspartate / pharmacology
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Phenylcarbamates / administration & dosage
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Phenylcarbamates / pharmacology*
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Propylene Glycols / administration & dosage
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Propylene Glycols / pharmacology*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Seizures / physiopathology
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Seizures / prevention & control*
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Synaptic Transmission / drug effects*
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Synaptic Transmission / physiology
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Triazines / administration & dosage
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Triazines / pharmacology*
Substances
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Anticonvulsants
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Phenylcarbamates
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Propylene Glycols
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Receptors, N-Methyl-D-Aspartate
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Triazines
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2-amino-4-methyl-5-phosphono-3-pentenoic acid
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Glutamic Acid
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N-Methylaspartate
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2-Amino-5-phosphonovalerate
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Kainic Acid
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Lamotrigine
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Felbamate