Synergistic interaction of gabapentin and oxcarbazepine in the mouse maximal electroshock seizure model--an isobolographic analysis

Eur J Pharmacol. 2005 May 16;515(1-3):54-61. doi: 10.1016/j.ejphar.2005.03.046.

Abstract

The anticonvulsant effects produced by mixtures of oxcarbazepine and gabapentin (two second-generation antiepileptic drugs) in numerous fixed-ratio combinations of 1:1, 1:2, 1:5, 1:10, 1:15, and 1:20 were examined isobolographically in the mouse maximal electroshock seizure model. Results displayed that mixtures of both drugs at the fixed-ratios of 1:2, 1:5, 1:10, 1:15, and 1:20 exerted supra-additive (synergistic) interactions against electroconvulsions. Only a fixed-ratio of 1:1 was indifferent with isobolography, although the combination displayed the trend towards supra-additivity. Furthermore, the combinations of oxcarbazepine with gabapentin, administered at their median effective doses (ED(50 mix)s), did not alter motor performance of animals challenged with the chimney test. Additionally, neither gabapentin nor oxcarbazepine affected total brain concentrations of co-administered drug, indicating a pharmacodynamic nature of interaction between these antiepileptics. Finally, based on preclinical data presented here the combination of oxcarbazepine and gabapentin is of particular importance for further therapy in patients with refractory partial seizures.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / administration & dosage
  • Amines / pharmacokinetics
  • Amines / therapeutic use*
  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use*
  • Brain / metabolism
  • Carbamazepine / administration & dosage
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / pharmacokinetics
  • Carbamazepine / therapeutic use*
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / pharmacokinetics
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Electroshock / adverse effects
  • Gabapentin
  • Male
  • Mice
  • Oxcarbazepine
  • Psychomotor Performance / drug effects
  • Seizures / etiology
  • Seizures / prevention & control*
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / pharmacokinetics
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • Carbamazepine
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Oxcarbazepine