Effects of Clopidogrel on the Anticonvulsant Efficacy of Valproic Acid and Levetiracetam in a PTZ-Induced Seizure Model

Patients with cerebrovascular disease frequently require concomitant antiplatelet and antiseizure therapy. However, experimental evidence regarding potential pharmacodynamic interactions between these medications remains limited. The present study investigated whether clopidogrel affects the anticonvulsant effects of valproic acid (VPA) or levetiracetam (LEV) in a pentylenetetrazol (PTZ)-induced seizure model. Forty-two male Wistar rats were randomly allocated to seven groups (n = 6/group): Control, PTZ, clopidogrel (CLP), VPA, LEV, VPA + CLP + PTZ, and LEV + CLP + PTZ. Electroencephalographic recordings, passive avoidance testing, histopathological examination, and glial fibrillary acidic protein (GFAP) immunohistochemistry were performed to evaluate seizure activity, behavioral performance, neuronal injury, and astroglial activation. Both VPA and LEV significantly reduced spike–wave discharge frequency and duration compared with the PTZ group (p < 0.05). Clopidogrel alone did not exhibit anticonvulsant activity, and co-administration with either VPA or LEV did not significantly alter electrophysiological, behavioral, histopathological, or GFAP-associated immunohistochemical outcomes. Overall, these findings indicate that clopidogrel did not significantly affect the anticonvulsant efficacy of VPA or LEV under the experimental conditions of this acute PTZ-induced seizure model.