Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model
In: Epilepsy Research, Jg. 90 (2010-08-01), Heft 3, S. 188-198
Online
academicJournal
Zugriff:
Summary: The aim of this study was to characterize the anticonvulsant effects of stiripentol (STP) in combination with clobazam [CLB], and valproate [VPA]) in the mouse maximal electroshock (MES)-induced seizure model using the type I isobolographic analysis for parallel and non-parallel dose–response relationship curves (DRRCs). Potential adverse-effect profiles of interactions of STP with CLB and VPA at the fixed-ratio of 1:1 in the MES test with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. In the mouse MES model, STP administered singly had its DRRC non-parallel to that for CLB and, simultaneously, parallel to that for VPA. With type I isobolography for parallel DRRCs, the combinations of STP with VPA at three fixed-ratios of 1:3, 1:1 and 3:1 exerted sub-additive (antagonistic) interaction. Isobolography for non-parallel DRRCs revealed that the combination of STP with CLB at the fixed-ratio of 1:1 produced additive interaction. For all combinations, neither motor coordination, long-term memory nor muscular strength was affected. Total brain antiepileptic drug concentrations revealed bi-direction changes with the most profound being an 18.6-fold increase in CLB by STP and a 2.3-fold increase in STP by VPA. In conclusion, the additive interaction between STP and CLB was associated with a concurrent pharmacokinetic interaction and these data may explain the clinical efficacy seen with this combination. In contrast, the antagonism between STP and VPA was surprising since synergism is observed clinically. [Copyright &y& Elsevier]
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Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model
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Autor/in / Beteiligte Person: | Luszczki, Jarogniew J. ; Trojnar, Michal K. ; Ratnaraj, Neville ; Patsalos, Philip N. ; Czuczwar, Stanislaw J. |
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Zeitschrift: | Epilepsy Research, Jg. 90 (2010-08-01), Heft 3, S. 188-198 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 0920-1211 (print) |
DOI: | 10.1016/j.eplepsyres.2010.04.006 |
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