Evaluation of anti epileptic effect of conjugated form of valproic acid and phenytoin in mice

The drugs that are currently available for treatment of epilepsy are far from perfect, and the side effects that accompany the use of these drugs are also quite significant in some cases. Therefore, there is a great demand for the design of novel, effective antiepileptic drugs to combat epilepsy in its various forms. The aim of this study was to synthesize and test the anticonvulsant activity of the conjugate of valproic acid and phenytoin in mice. The maximal electroshock seizure (MES) and kainic acid test were used. The MES model involves the induction of seizures through the application of an alternating current using ear-clip electrodes whereas the kainic acid seizure was generated chemically by injection of kainic acid. Neurotoxicity (at administered dose) is reported using the locomotor activity test. In the MES model of seizure, the intraperitoneal administration of phenytoin, valporic acid and the conjugate of them protected against the induction of seizure with different ED50 values (15.2 kg/mg, 293.8 kg/mg and 13.5 kg/mg, respectively). In the kainic acid model of seizures, only valporic acid (at doses greater than 300 mg/kg) was effective in protecting against the induction of seizures. No significant effects were observed on locomotor activity by any of the compounds tested. The results of this study showed that there is not a significant difference between the effectiveness of the compounds tested in protecting against the MES induced seizures.