期刊
PHARMACOLOGY
卷 97, 期 5-6, 页码 259-264出版社
KARGER
DOI: 10.1159/000444452
关键词
Antiepileptic drugs; Isobolographic analysis; Maximal electroshock; Three-drug combination
资金
- Medical University of Lublin (Poland) [DS474/2012-2014]
Background/Aims: To characterize the anticonvulsant effects of a combination of 3 antiepileptic drugs (AEDs; i.e. carbamazepine (CBZ), phenobarbital (PB) and topiramate (TPM)) at the fixed-ratio of 1: 1: 1 in the mouse maximal electroshock (MES)-induced seizure model. Methods: Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Type I isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to analyze the 3-drug combination. Results: In the mouse MES model, all the studied AEDs (i.e. CBZ, PB and TPM) administered singly had their DRRCs parallel to each other. With type I isobolography for parallel DRRCs, a combination of CBZ, PB and TPM at the fixed-ratio of 1: 1: 1 exerted supra-additive (synergistic) interaction in the mouse MES model. Conclusions: Synergistic interaction among CBZ, PB and TPM at the fixed-ratio of 1: 1: 1 against MES-induced seizures is worthy of consideration in further clinical settings. All detailed calculations required to perform type I isobolographic analysis for the 3-drug combination were presented. (C) 2016 S. Karger AG, Basel
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