RESEARCH PAPER
Diltiazem enhances the protective activity of oxcarbazepine against maximal electroshock-induced seizures in mice
| 1 | Department of Pathophysiology, Medical University, Lublin, Poland |
| 2 | Department of Cardiology, Medical University, Lublin, Poland |
| 3 | Department of Internal Medicine, Medical University, Lublin, Poland |
| 4 | Department of Obstetrics and Perinatology, Medical University, Lublin, Poland |
| 5 | Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland |
CORRESPONDING AUTHOR
Jarogniew J. Łuszczki
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2008;2(2):147–152
KEYWORDS
calcium channel antagonistdiltiazemoxcarbazepinemaximal electroshock seizure chimney testprotective indexpharmacodynamic interaction
ABSTRACT
The aim of the study was to assess the eff ect of diltiazem (a calcium channel antagonist) on the anticonvulsant activity
and acute adverse-eff ect potential of oxcarbazepine (a second-generation antiepileptic drug) in the maximal
electroshock seizure (MES) model and chimney test in mice. Total brain concentrations of oxcarbazepine were
measured with high pressure liquid chromatography (HPLC) to ascertain any pharmacokinetic contribution to the
pharmacodynamic interaction between drugs. Results indicate that diltiazem (at a dose of 5 mg/kg, i.p.) signifi cantly
enhanced the anticonvulsant activity of oxcarbazepine in the MES test in mice, by reducing the median eff ective dose
(ED50 value) of oxcarbazepine from 14.25 to 9.87 mg/kg (P<0.01). In contrast, diltiazem at lower doses of 1.25 and 2.5
mg/kg had no signifi cant impact on the antiseizure action of oxcarbazepine in the MES test in mice. In the chimney
test, diltiazem (up to 5 mg/kg, i.p.) did not signifi cantly aff ect the acute adverse eff ect potential of oxcarbazepine,
and the median toxic dose (TD50 value) of the studied antiepileptic drug ranged from 74.16-62.91 mg/kg. Moreover,
diltiazem (5 mg/kg) did not signifi cantly alter total brain oxcarbazepine concentrations as measured with HPLC. In
conclusion, diltiazem ameliorates the pharmacological profi le of oxcarbazepine, when considering both the antiseizure
and acute adverse eff ects of the antiepileptic drug in preclinical study on animals. The observed interaction between
oxcarbazepine and diltiazem in the MES test was pharmacodynamic in nature; therefore, this favourable combination
deserves more attention from a clinical point of view
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