Effects of the combination of valproate and ethosuximide on spike wave discharges in WAG/Rij rats

Epilepsy Research
C M van RijnHarry Meinardi

Abstract

We studied the interaction between valproate (VPA) and ethosuximide (ESM) in diminishing the incidence of absence-like spike-wave discharges (SWDs) in the EEG of WAG/Rij rats. VPA, ESM, their combination and saline were evaluated in 16 rats. The doses of VPA ranged from 0 to 280 mg/kg and the doses of ESM ranged from 0 to 40 mg/kg. For the drug combination, a fixed weight ratio of 7/1 VPA/ESM was used. The incidence of SWDs in the EEG was determined for the period of 15-75 min after injection and compared to the incidence of SWDs prior to injection. The sigmoid-E(max) equation was fitted to the data. Isobolic analysis, on 50% effect, was used to assess the character of the drug interaction. The parameters for diminishing the incidence of the SWDs were: VPA: ED(50): 121mg/kg; ESM: ED(50): 21.5mg/kg; VPA/ESM: ED(50): 112/16 mg/kg. Isobolic analysis showed that a higher drug load was needed of the combination than of the individual drugs to achieve a 50% reduction of SWDs: factor 1.67; P = 0.012. The interaction between valproate and ethosuximide was shown to be infra-additive in diminishing the incidence of SWDs in WAG/Rij rats.

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Citations

Aug 24, 2007·Clinical and Experimental Pharmacology & Physiology·Olivera P StanojlovićVeselinka T Susić
Mar 1, 2012·International Journal of Clinical Pharmacology and Therapeutics·Michael Bewernitz, Hartmut Derendorf
Feb 7, 2013·Brain & Development·Hideaki ShiraishiHiroshi Otsubo
Jul 14, 2007·CNS Drug Reviews·M Zafer Gören, Filiz Onat
May 15, 2016·Pharmacology, Biochemistry, and Behavior·Valerio D'AmoreGilles van Luijtelaar
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claudio PirozziRosaria Meli

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