Antioxidant Effect of Levetiracetam and Brivaracetam Acting on Presynaptic SV2A Receptors: An In-vitro Study

Abstract

Introduction: Epilepsy is a serious psychological condition associated with social stigma, psychiatric co-morbidity, and a high economic burden. It is pertinent to develop novel treatment methods given the ever-evolving nature of the disease. Recently, various newer Antiepileptic Drugs (AEDs) have been under study, among which a newer targeted modality consists of SV2A receptors. Aim: To compare the antioxidant properties or free radical scavenging activity of the newer heterogeneous AEDs acting on the SV2A receptors, namely Levetiracetam (LEV) and Brivaracetam (BRV). Materials and Methods: This in-vitro study was conducted at Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India from July 2021 to August 2021. The study evaluated the antioxidant properties of LEV and BRV using various assays such as the Ferric Reducing Antioxidant Power (FRAP) test, DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, Nitric Oxide (NO) radical scavenging assay, Superoxide Dismutase activity (SOD), and catalase activity. The obtained results were expressed using specific formulas related to the absorbance of the respective chemicals, along with the percentage of inhibition, and have been tabulated in Microsoft excel Sheet Version 16.16.27. Halfmaximal Inhibitory Concentration (IC50) values were calculated using scatter plot graphs. Results: The FRAP values for LEV were reported to be significantly higher compared to BRV at concentrations of 20, 40, 60, 80 μg/mL, while at 100 μg/mL, BRV showed better ferric reducing activity. Although both drugs exhibited antioxidant activity, the results clearly identified LEV as a better NO radical scavenger, with a percentage of inhibition reaching up to 80.52%. During the SOD assay, the percentage inhibition of superoxide generation by LEV was found to be 99.02%, while that of BRV was 97.07% at a concentration of 100 μg/mL. LEV (0.573) also showed a higher degradation of H2O2 per minute than BRV (0.065) at a concentration of 100 μg/mL. Conclusion: The results showed that both drugs, BRV and LEV, exhibited significant antioxidant capacity. However, LEV demonstrated increased antioxidant potency and efficacy compared to BRV.