Épilepsie - page 3 - Publications Scientifiques

Dernière publication 30/08/2010

Interactions of stiripentol with clobazam and valproate in the mouse maximal ele

The aim of this study was to characterize the anticonvulsant effects of stiripentol (STP) in combination with clobazam [CLB], and valproate [VPA])...

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    [title] => Interactions of stiripentol with clobazam and valproate in the mouse maximal ele
    [paragraph] => Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model. 
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Authors
J. Luszczki, M. Trojnar, N. Ratnaraj, P. Patsalos, S. Czuczwar. 

 Lab
Medical University of Lublin, Department of Pathophysiology, Lublin, Poland.
Journal
Epilepsy Research
Abstract
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.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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