Effect of Diclofenac, Meloxicam and their Interaction with Diazepam in Lithium-Pilocarpine Induced Status Epilepticus in Mice

Abstract

Background: Status Epilepticus (SE) is a neurological emergency that necessities rapid control to prevent its bad sequelae. Benzodiazepines, like diazepam and lorazepam, are widely used drugs to terminate seizure activity but SE becomes more refractory to these agents. SE causes cyclooxygenase-2 (COX-2) induction and pharmacological targeting of specific pro-inflammatory pathways after SE may show antiepileptogenic effects.

This work was designed to study the effect of two COX inhibitors: diclofenac and meloxicam, as well as their interaction with diazepam on lithium-pilocarpine model of SE in mice.

Methods: Fifty-six mice were randomly divided into 7 equal groups; control, lithium-pilocarpine, diclofenac, meloxicam, diazepam, diclofenac-diazepam and meloxicam-diazepam groups. All groups, except control, were injected with pilocarpine, 24 hrs after lithium chloride, to induce SE. Latency period to first seizures, percentage of convulsed and protected mice as well as death rate were recorded. At the end, TNF-α, IL-1β and PGE2 levels were assessed in brain homogenate.

Results: Diazepam and diclofenac-diazepam, meloxicam-diazepam groups were protected from convulsion and death while diclofenac or meloxicam alone increased the latency to seizures with partial protection from convulsions and death. SE increased levels of TNF-α, IL-1β and PGE2 in brain tissue while, diclofenac, meloxicam and diazepam decreased their levels. The later effect was enhanced by diclofenac-diazepam and meloxicam-diazepam combinations.

Conclusion: Diclofenac and meloxicam have anticonvulsant effect that was enhanced by combination with diazepam and effect could be attributed partially to their anti-inflammatory action.