Isobolographic and behavioral characterizations of interactions between vigabatrin and gabapentin in two experimental models of epilepsy

European Journal of Pharmacology
Jarogniew J LuszczkiS J Czuczwar

Abstract

The aim of this study was to characterize the pharmacodynamic, pharmacokinetic and adverse-effect profiles of vigabatrin and gabapentin. Isobolographic analysis was used in two mouse experimental models of epilepsy: the maximal electroshock seizure threshold test and pentylenetetrazole-induced seizures. In the maximal electroshock seizure threshold test, electroconvulsions were produced by a current with various intensities whilst in the pentylenetetrazole test a CD(97) dose (100 mg/kg) was used. Potential adverse-effect profiles of interactions of vigabatrin with gabapentin at three fixed-ratios of 1:3, 1:1 and 3:1 from both seizure tests were evaluated in the chimney (motor performance) and grip-strength (skeletal muscular strength) tests. Vigabatrin and gabapentin total brain concentrations were determined with high performance liquid chromatography. Vigabatrin and gabapentin administered singly increased the electroconvulsive threshold (TID(20) - 226.2 and 70.0 mg/kg, respectively). With isobolography, the combination of vigabatrin with gabapentin at the fixed-ratio of 1:3 exerted supra-additive (synergistic) interactions whilst at 1:1 and 3:1 additivity occurred. Similarly, vigabatrin and gabapentin administered singly sup...Continue Reading

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Citations

Jul 26, 2010·Pharmaceuticals·Jong Woo Lee, Barbara Dworetzky
Jun 16, 2012·Expert Review of Clinical Pharmacology·Cecilie Johannessen Landmark, Philip N Patsalos
Feb 13, 2009·Expert Opinion on Drug Metabolism & Toxicology·Stanislaw J CzuczwarMarek Kacinski
May 24, 2011·Pharmacological Reports : PR·Władysław LasońStanisław J Czuczwar
Mar 1, 2016·Expert Opinion on Drug Discovery·Krzysztof ŁukawskiStanisław J Czuczwar
Jul 20, 2018·Expert Review of Clinical Pharmacology·Barbara BłaszczykStanisław J Czuczwar
Feb 13, 2020·Pharmacological Reports : PR·Mariusz J ŚwiąderStanisław J Czuczwar
Dec 20, 2020·Expert Review of Neurotherapeutics·Krzysztof Łukawski, Stanisław J Czuczwar
Jun 3, 2021·International Journal of Molecular Sciences·Katarzyna Załuska-OgryzekJarogniew J Łuszczki

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