Comparison of Bumetanide, Levetiracetam and Sodium Valproate Effects on Convulsions and Motor Coordination in Experimental Models

Mohammed Alharbi, Hussein Ali, Ahmad Alhowail, Bader Algohane and Hossam Elsisi

Background and Objective: Given the high prevalence of adverse effects with current antiepileptic drugs and limited understanding of their mechanisms, this study aimed to evaluate the anticonvulsant effects, neurotoxic profiles and mechanisms of Bumetanide, Levetiracetam and Valproate (VAL, in rodent epilepsy models). Materials and Methods: A study with 72 mice and 24 rats assessed convulsions and motor coordination using MES and PTZ models. Brain biomarkers (GABA, Glutamate, NKCC1 and GABA transaminase) were measured by ELISA. Mice were divided into four groups for MES and Rota rod tests and rats into four groups for biomarker analysis. Drugs were administered intraperitoneally 30 min before testing. Statistical analysis was performed using GraphPad Prism^® version 8. Results: In the MES test, BUM exhibited moderate anticonvulsant effects but was less effective than LEV and VAL. The LEV and VAL significantly reduced seizure duration, with VAL showing superior efficacy. In the PTZ model, all three drugs delayed convulsion onset, with VAL demonstrating the strongest effect. In the Rota rod test, BUM did not impair motor coordination, while both LEV and VAL caused ataxia, with VAL having the highest effect. The BUM increased GABA levels and decreased GABA transaminase and NKCC1 expression, suggesting chloride homeostasis modulation. The LEV influenced chloride homeostasis without altering GABA levels, while VAL enhanced GABA levels and inhibited GABA transaminase. Conclusion: The VAL was the most effective anticonvulsant, followed by LEV, with BUM showing moderate effects. The BUM had the safest neurotoxic profile. The VAL’s potency was linked to GABAergic mechanisms, while LEV’s effects were likely due to SV2A modulation. Bumetanide’s effects are linked to chloride homeostasis regulation.

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