Effect of diclofenac and paracetamol on anticonvulsant activity of phenytoin and sodium valproate in laboratory animals

Background: Neuroinflammation is a major contributor to neurological and neurodegenerative diseases, and inflammatory processes have been implicated in both acute and chronic conditions such as epilepsy. Cyclooxygenase (COX) inhibitors, are used largely to treat febrile condition, pain state and inflammation, through their role in the inhibition of prostaglandin synthesis. Thus, drugs that reduce the production of prostaglandins may have beneficial effect in epilepsy.

Objective: The present study is aimed at evaluating possible effects of diclofenac and paracetamol on the anticonvulsant outcome of phenytoin and sodium valproate in chicks and mice.

Methods: Electrically and chemically-induced seizure models, using maximal electroshock test (MEST) in chicks and pentylenetetrazole (PTZ) test in mice, respectively, were used for the study.

Results: Co-administration (i.p.) of diclofenac (20 mg/kg) and paracetamol (100 mg/kg), each with phenytoin (15 mg/kg, i.p.), potentiated the anticonvulsant outcome of phenytoin in MEST. Diclofenac-phenytoin and paracetamol-phenytoin administrations exhibited 90% and 80% protection, respectively, as against the 0% protection produced when diclofenac and paracetamol were administered alone. Similarly, there was statistical significant decrease (p<0.05) in the recovery time from seizures between the groups coadministered with the two drugs and those that received individual drugs. In PTZ-induced seizure test, there was slight decrease in seizure protection (60%); with significant increase (p<0.05) in the mean onset of seizures when diclofenac (20 mg/kg) and sodium valproate (100 mg/kg) were co-administered; while valproate (100 mg/kg) exhibited 80% protection with no significant increase (p<0.05) in the mean onset of seizures. Also, similar protection of 80% was obtained when paracetamol (100 mg/kg) and valproate (100 mg/kg) were co-administered showing no potentiation or antagonism in PTZ-induced seizure test.

Conclusion: The results of this study showed potentiating effect when diclofenac and phenytoin; paracetamol and phenytoin, were co-administered. Therefore, the co-administration may be beneficial in generalized tonic-clonic seizures.