Comparative Docking Study of Gamma-Aminobutyric Acid Receptor Subunit Alpha-۱ Interactions with Approved and Emerging Antiepileptic Drugs

Epilepsy is a prevalent neurological disorder characterized by recurrent seizures resulting from abnormal brain activity, affecting around ۱% of the global population. The GABA-A receptor, a critical mediator of inhibitory neurotransmission, is a key target for antiepileptic drugs (AEDs) aimed at restoring the excitation-inhibition balance in the brain. This study utilized molecular docking to investigate interactions between ten antiepileptic drugs-five approved (Gaboxadol, Allopregnanolone, Cenobamate, Topiramate, Clobazam) and five emerging (Zolpidem, Eszopiclone, Suvorexant, Lemborexant, Bretazenil)-with the GABA-A receptor α۱ subunit. Docking simulations were performed using AutoDock Vina, with results analyzed to assess binding affinities, hydrogen bonds, and other molecular interactions. Findings reveal that emerging drugs such as Zolpidem, Suvorexant, and Lemborexant exhibit strong binding affinities comparable to approved AEDs, suggesting their potential to enhance seizure management. The study highlights diverse interaction profiles, including significant hydrogen bonding and hydrophobic interactions, which contribute to the stabilization of drug-receptor complexes. Insights gained from this study could guide the development of more selective and effective treatments for epilepsy, addressing the limitations of current therapies.

کلیدواژه ها:

GABA-A receptor α۱ subunit ، Antiepileptic drugs ، Molecular Docking ، AutoDock Vina