Stiripentol in a dose-dependent manner elevates the threshold for maximal electroshock-induced seizures in mice
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Department of Pathophysiology, Medical University, Lublin, Poland
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
Department of Neurology, Neuropsychiatric Hospital, Kielce, Poland
JPCCR 2007;1(2):155–157
The aim of the study was to determine the effect of stiripentol (STP) on the threshold for maximal electroshock (MEST)-induced seizures in mice. STP is a novel anti-epileptic drug recently approved for the treatment of patients with myoclonic seizures and children with Dravet syndrome. Electroconvulsions were induced in mice by means of an alternating current (50 Hz, 500 V, ear-clip electrodes, 0.2 s stimulus duration, tonic hind limb extension taken as the endpoint). Linear regression analysis of STP doses and their corresponding threshold increases allowed determination of threshold increasing doses by 20% and 50% (TID[sub]20[/sub] and TID[sub]50[/sub] values) which elevate the threshold in drug-treated animals over the threshold for control animals. Results indicate that STP administered systemically (i.p.), 60 min. before the MEST test, increased in a dose-dependent manner the threshold for MEST-induced seizures in mice. STP at 200 mg/kg significantly elevated the threshold for MEST-induced seizures (P<0.001). Similarly, STP at lower doses of 50, 100 and 150 mg/kg also increased the threshold for MEST-induced seizures, although these results did not attain statistical significance. The experimentally-derived TID[sub]20[/sub] and TID[sub]50[/sub] values for STP were 103.2 and 195.8 mg/kg, respectively. Based on this pre-clinical study, one can ascertain that STP dose-dependently increased the threshold for MEST-induced seizures, allowing determination of TID[sub]20[/sub] and TID[sub]50[/sub] values.
Jarogniew J. Łuszczki   
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
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