Epilepsy is one of the commonly occurring chronic neurological disorders which involves abnormal electrical
impulses in the brain. It is characterized by the sudden loss of consciousness, followed by abnormal shaking of the body.
Though there are various types of antiepileptic drugs available clinically, the treatment of epilepsy still remains
inadequate because of their toxicity and idiosyncratic side effects. Thus, there is unmet medical need to develop safe
drugs for the treatment of epilepsy with lower side effects and improved bioavailability profiles. Considering the
structural similarity between phenytoin/lamotrigine, a series of 1,3,4-thiadiazole was designed based on molecular
docking study into the active site of the voltage-gated sodium channels. Antiepileptic activity of the synthesized
compounds was evaluated in rats by maximal electroshock induced seizures (MES) model at different doses. Among the
tested compounds, some exhibited significant anticonvulsant activity as compared to phenytoin in a dose-dependent
manner. The neurotoxicity study was carried out using the rotarod test and the results of which suggests that the target
compounds are safe and could be further developed as potential lead for antiepileptic drugs.
Keywords: Antiepileptic activity, docking study, epilepsy, green synthesis, neurotoxicity, thiadiazole.
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