Topiramate, as Prominent Dual Inhibitor, Targeting Beta-secretase and Voltage-gated Sodium Channel

Abstract

Background: Alzheimer's disease (AD) is evidenced by decreased cognitive function and increased prevalence of seizures. The association of epilepsy with AD is of clinical importance. Besides, memory impairment is common in epilepsy patients. Anti-epilepsy drugs have been used in various neurodegenerative disorders other than epilepsy. Objective: To validate the assumption that an AED could be effective against AD. The therapeutic target in the cure of epilepsy is the voltage-gated sodium channel (VGSC), while beta-secretase (BACE) is a vital target in AD treatment. Materials and Methods: In this study, we describe the molecular interactions of topiramate with BACE and VGSC by “Autodock 4.2.” Free binding energy and inhibition constant of “topiramate-BACE” and “topiramate-VSC” interactions were found to be “−5.67 kcal/mol and 69.69 μM;” and “−5.64 kcal/mol and 73.88 μM,” respectively. Results: Both hydrophobic interactions and H-bond exhibit a vital role in the binding of topiramate with the BACE and VGSC. Conclusion: The study suggests that topiramate might act as a prominent dual inhibitor against BACE and VGSC, which may prove to be a promising treatment option for epilepsy-associated AD.