کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
319939 539633 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Interactions between zonisamide and conventional antiepileptic drugs in the mouse maximal electroshock test model
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Interactions between zonisamide and conventional antiepileptic drugs in the mouse maximal electroshock test model
چکیده انگلیسی

Despite the major advances in antiepileptic drug (AED) therapeutics, about one third of patients with epilepsy still do not have adequate seizure control with currently available AEDs when prescribed as monotherapy. Typically, in this setting polytherapy with two or more AEDs is used. Zonisamide (ZNS) is a new AED effective in the treatment of refractory epilepsy and since it is only prescribed in polytherapy regimens, its interactions with other AEDs is of particular importance. The aim of this study was to isobolographically determine interactions between ZNS and four conventional AEDs: carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA), in the mouse maximal electroshock (MES)-induced seizure model. The total brain concentrations of conventional AEDs and ZNS were measured with immunofluorescence and high-pressure liquid chromatography (HPLC), respectively, in order to determine any pharmacokinetic contribution in any observed interactions. With isobolography, synergistic interactions were observed for the combination of ZNS plus VPA and ZNS plus PHT at the fixed-ratio of 1:1, while additivity was observed for their combinations at the remaining dose ratios of 1:3 and 3:1. In contrast, the interactions between ZNS and PB and between ZNS and CBZ, applied at the fixed-ratios of 1:3, 1:1 and 3:1 proved to be additive. None of these AED combinations were associated with motor and long-term memory impairment. Furthermore, whilst brain AED concentrations were unaffected by ZNS, PHT significantly increased and PB reduced brain ZNS concentrations. Thus, the resultant interactions between ZNS and PHT and between ZNZ and PB were consequent to both pharmacodynamic and pharmacokinetic components. Finally, one can conclude that because of the synergistic pharmacodynamic interaction between ZNS and VPA, this combination might be useful in clinical practice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Neuropsychopharmacology - Volume 17, Issue 4, March 2007, Pages 265–272
نویسندگان
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