Diltiazem enhances the protective activity of oxcarbazepine against maximal electroshock-induced seizures in mice
Journal Title: Journal of Pre-Clinical and Clinical Research - Year 2008, Vol 2, Issue 2
Abstract
The aim of the study was to assess the effect of diltiazem (a calcium channel antagonist) on the anticonvulsant activity and acute adverse-effect 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.) significantly enhanced the anticonvulsant activity of oxcarbazepine in the MES test in mice, by reducing the median effective 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 significant 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 significantly affect the acute adverse effect 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 significantly 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 effects 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.
Authors and Affiliations
Anna Zadrożniak, Michał Trojnar, Marcin Trojnar, Żaneta Kimber-Trojnar, Monika Dudra-Jastrzębska, Marta Andres-Mach, Jarogniew Łuszczki
Keywords
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