Modulatory Effect of Pentazocine and Pethidine on Anticonvulsant Activity of Phenobarbitone in 4-Aminopyridine-Induced Seizures in Mice

Abstract

Management of epilepsy involved the use of many drugs, which sometimes include analgesics. Opioid analgesics being the second most commonly used drugs in insured epileptic patients are associated with neuro-excitation, ranging from nystagmus, extremity flexion, rigidity, myoclonus and seizures. The aim of this study was to investigate modulatory effect of opioid (Pentazocine and Pethidine) analgesics on 4-Aminopyridine (4-AP) induce seizure in mice. The anticonvulsant activity of Phenobarbitone (20 & 30 mg/kg), pentazocine (5 & 10 mg/kg) and pethidine (20 & 30 mg/kg) was evaluated using 4-AP-induced seizures in mice as well as co-administration between phenobarbitone and pentazocine or pethidine each. Phenobarbitone at doses of 20 & 30 mg/kg offered 80 and 100% seizure protection respectively. Pentazocine 10 mg/kg showed slight anticonvulsant effect with 20% protection but 5 mg/kg didn't. While Pethidine (30 mg/kg) provided 20% protection with no protection at 20 mg/kg. Co-administration of phenobarbitone (20 mg/kg) and pentazocine (10 mg/kg) abolished the effect observed with phenobarbitone alone. When phenobarbitone 20 mg/kg was interacted with pethidine (20) produced 0% protection by reversing the earlier protection obtained by phenobarbitone alone. In conclusion, pentazocine and pethidine have been shown to antagonize anti-seizure activity of phenobarbitone when coadministered in 4-AP-induced seizures in mice.