Comprehensive Bioinformatics, Molecular Docking, and In Vivo Investigation of a Novel Mechanistic Pathway in Pentylenetetrazole-Induced Seizures

Epilepsy affects millions worldwide; yet, approximately one-third of patients remain refractory to current therapies, indicating critical gaps in the understanding of seizure mechanisms. This study explored molecular pathways underlying pentylenetetrazole-induced seizures using an integrated approach of bioinformatics, molecular modeling, and in vivo validation. Network analysis identified twenty potential gene targets linking pentylenetetrazole to seizure pathways, with hydroxysteroid dehydrogenase and glutamate receptor ionotropic kainate emerging as key hub proteins involved in neurosteroid metabolism and excitatory neurotransmission. Computational analysis characterized pentylenetetrazole's molecular properties and demonstrated binding interactions with both identified targets, suggesting coordinated modulation of inhibitory and excitatory systems. In vivo experiments in Wistar rats demonstrated dose-dependent seizure induction and hippocampal injury. These findings establish hydroxysteroid dehydrogenase and glutamate receptor ionotropic kainate as novel therapeutic targets in pentylenetetrazole-induced seizures, providing mechanistic insights that may inform treatment strategies for refractory epilepsy.

کلیدواژه ها:

Mechanistic pathway ، PTZ-induced seizure ، network pharmacology ، Molecular docking ، In vivo study