Anticonvulsant Effect of Nebivolol alone and in Combination with Phenytoin against Maximal Electroshock-Induced Seizures in Mice

Abstract

Introduction: Phenytoin is widely used in treatment of generalised tonic clonic seizures but its adverse effects make its usage limited. Hence forth, there is a need for newer antiepileptics. Studies have shown antiepileptic property for nebivolol in combination with phenytoin hence, reducing the dosage of phenytoin and its adverse effects and toxicities. Aim: To evaluate the anticonvulsant property of nebivolol alone and in combination with phenytoin against Maximal Electroshock Seizures (MES) in a mouse model. Materials and Methods: This was an experimental animal study on total of 36 swiss albino male mice were randomly assigned to six groups with six animals in each group in December 2019 at Sri Manakula Vinayagar Medical College and Hospital. Group 1 was considered as normal control, Group 2 received Phenytoin 25 mg/kg Intraperitoneal (IP); Group 3 & 4 received Nebivolol 0.25 mg/kg oral & 0.50 mg/kg oral, respectively; Group 5 received 12.5 mg/kg IP and nebivolol 0.25 mg/kg oral; Group 6 received Phenytoin 12.5 mg/kg IP and nebivolol 0.50 mg/kg oral. Anticonvulsant effect of the drugs nebivolol and phenytoin was elicited in mice by MES test. After induction following parameters were recorded for onset of Tonic Hind Limb Extension (THLE), duration of clonus, duration of THLE, number of jerks, recovery time. Statistical analysis was done by ANOVA followed by post-hoc Dunnett t-test. Results: Significant reduction in duration of THLE (p<0.01) and clonus (p<0.001) was observed in the group treated with phenytoin (12.5 mg/kg) and nebivolol (0.50 mg/kg). Conclusion: The present study concludes that the lower dose of phenytoin in combination with nebivolol can reduce seizures induced by MES in mice model.