Protective Effects of Mefenamic Acid against Pentylenetetrazol-Induced Seizures: An Experimental Study

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures due to abnormal electrical activity in the brain. Despite advancements in treatment, approximately 30% of patients remain unresponsive to current antiepileptic drugs (AEDs), highlighting the need for alternative therapies. Mefenamic acid (MFA), a nonsteroidal anti-inflammatory drug (NSAID), has shown potential anticonvulsant properties, possibly through modulation of GABAA receptors and adenosine signaling. Objective: This study aimed to evaluate the anticonvulsant effects of MFA in a pentylenetetrazol (PTZ)-induced seizure model in mice, focusing on its possible mechanisms of action. Methods: Male NMRI mice were administered MFA at doses of 5, 10, and 15 mg/kg i.p40 minutes before PTZ (80 mg/kg i.p.) to induce seizures. Diazepam served as a standard drug, and caffeine was used to investigate adenosine receptor modulation. Seizure onset, duration, and severity were recorded. Data were analyzed using one-way ANOVA followed by Tukey’s post-hoc test. Results: MFA at 5 mg/kg significantly delayed seizure onset and provided complete protection against PTZ-induced seizures, with results comparable to diazepam. Higher doses (10 and 15 mg/kg) delayed seizure latency but were less effective in reducing seizure duration. The addition of caffeine nullified MFA's protective effects, suggesting adenosine A1 receptor involvement. Conclusion: MFA, particularly at 5 mg/kg, exhibits significant anticonvulsant effects in a PTZ-induced seizure model, likely through GABAergic modulation and adenosine A1 receptor interaction. These findings suggest MFA as a potential adjunctive therapy for epilepsy, warranting further investigation.