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Influence of osthole on the anticonvulsant activity of phenytoin and valproate in the maximal electroshock-induced seizures ...

Annales UMCS, Sectio DDD, Pharmacia, Vol. XXIV, N 3, 4

JAROGNIEW J. ŁUSZCZKI 1,2, TADEUSZ MARCZEWSKI 1, LECH P. MAZURKIEWICZ1,2,
SŁAWOMIR KARWAN2, MAJA TERESIŃSKA2, MAGDALENA FLOREK-ŁUSZCZKI3, MICHAŁ GLEŃSK4

1 Department of Pathophysiology, Medical University of Lublin, Poland
2 Isobolographic Analysis Laboratory, Institute of Agricultural Medicine, Lublin, Poland
3 Department of Public Health, Institute of Agricultural Medicine, Lublin, Poland
4 Department of Pharmacognosy, Wroclaw Medical University, Wroclaw, Poland

Abstract

Influence of osthole on the anticonvulsant activity of phenytoin and valproate in the maximal electroshock-induced seizures in mice
 
Accumulating evidence indicates that some naturally occurring substances extracted from plants and herbs possess anticonvulsant properties. One of these substances is osthole isolated from Peucedanum ostruthium (L.) Koch. Therefore, the aim of this study was to determine the effect of osthole on the anticonvulsant activity of two classical antiepileptic drugs (AEDs: phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock seizure (MES) model. Electroconvulsions (tonic-clonic seizures) were evoked in adult Albino Swiss mice by a current (25mA, 50Hz, 500V, 0.2s stimulus duration,) delivered via auricular electrodes. Adverse-effect profiles of the combination of osthole with PHT and VPA with respect to motor performance, long-term memory and skeletal muscular strength were measured. Total brain concentrations of PHT and VPA were estimated to characterize the interaction profile between osthole and classical AEDs. Results indicate that osthole administered intraperitoneally (i.p.) at doses of 50, 100 and 150 mg/kg did not significantly affect the protective action of PHT and VPA in the MES test in mice. Moreover, osthole in combination with PHT and VPA did not alter motor performance, long-term memory or skeletal muscular strength in experimental animals. Additionally, osthole had no significant impact on total brain concentrations of PHT and VPA in mice. The present study demonstrates that osthole had no significant effect on the anticonvulsant action of PHT and VPA in the mouse MES model. If the results from this study could be extrapolated into clinical settings, osthole combined with PHT and VPA would offer neutral pharmacodynamic interaction.

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Keywords

Osthole, phenytoin, valproate, maximal electroshock seizure test

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