Evaluating Anticonvulsant and Neuroprotective potentials of New Hydantoin Derivatives in PTZ and MES Models

Epilepsy is considered the most common neurological disease globally, characterized by recurrent unprovoked seizures. The primary treatment for epilepsy involves therapy with antiepileptic drugs to control seizures. However, therapeutic options for this condition are limited, and many of these drugs have various side effects on the central nervous system, leading to cognitive impairment. Therefore, the development of new effective agents with anti-seizure activity and mild side effects remains a significant challenge. In this study, we aimed to investigate the anticonvulsant and neuroprotective activities of several new derivatives of hydantoin, namely (D,L)-5-((1H-Indol-3-yl)methyl)imidazolidine-2,4-dione (ART 2), lithium salt of 5,5-diphenylimidazolidine-2,4-dione (ART 5), lithium salt of (D,L)-5-benzylimidazolidine-2,4-dione (ART 1215), and lithium salt of (D,L)-5-((1H-indol-3-yl)methyl)imidazolidine-2,4-dione (ART 2125). The anticonvulsant properties of these compounds were evaluated using pentylenetetrazol (PTZ) and maximal electroshock seizure (MES) models. Additionally, the neuroprotective activity of the compounds was assessed through histopathological examination of the hippocampus and entorhinal cortex with and without PTZ administration. Our findings indicate that the new derivatives of hydantoin exhibit greater efficacy in treating clonic seizures and have lower toxicity and myorelaxation compared to phenytoin. Among the tested compounds, ART 5 and ART 1215 not only mitigated PTZ-induced damage but also preserved neuronal integrity in the hippocampus and entorhinal cortex, indicating their potent neuroprotective effects.