Effect of N-(p-ethoxycarbonylphenylmethyl) -p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

Abstract

Introduction and objective. The purpose of this study was to determine the effects of N-(p-ethoxycarbonylphenylmethyl)p-isopropoxyphenylsuccinimide (ECPM-IPPS), a new succinimide derivative, on the protective action of four classical antiepileptic drugs (AEDs): carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT) and valproate (VPA) in the mouse maximal electroshock (MES)-induced tonic seizure model. Materials and 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 ear-clip electrodes. Results. ECPM-IPPS administered (i.p.) at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice (P<0.05). Lower doses of ECPM-IPPS (50 and 100 mg/kg) had no significant impact on the threshold for electroconvulsions in mice. Moreover, ECPM-IPPS (100 mg/kg) did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the MES test in mice. Conclusions. ECPM-IPPS elevated the threshold for electroconvulsions in mice in a dose-dependent manner. However, ECPM-IPPS (100 mg/kg) did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of ECPM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.