Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Pharmacology

Introduction: This study was designed to evaluate the anti-epileptic effect of flupirtine versus diazepam, as a monotherapy or in combination with celecxib,in models of generalized epilepsy and status epilepticus in mice. Materials and methods: Two models were applied; model A: pentylenetetrazole induced generalized seizures and model B: pilocarpine induced status epilepticus. Mice recieved: 1: normal saline,2: DMSO 10%, 3: diazepam, 4: flupirtine,5: celecoxib,6: combined diazepam & celecoxib,7: combined flupirtine & celecoxib. To score behavioral seizures and EEG changes,modified racine scale was used. Biochemical studies were done to measure brain GABA and IL-6 levels. Cresyl violet stain and GFAP immunohistochemistry were done to evaluate neuronal cell damage and glial responses respectively.Results: Diazepam and flupirtine prolonged latency period to 1st seizure. Diazepam showed better results than flupirtine in the pharmacological parameters, almost the same results in biochemical parameters, while flupirtine showed better histopathological results. The best results were found in the group receiving combined diazepam and celecoxib.Conclusion: Diazepam, flupirtine and celecoxib posses anticonvulsant, immuno-modulatory and neuroprotective effects.Flupirtine is a promising drug that could contribute to the control of generalized seizures and status epilepticus.Celecoxib- diazepam combination improves diazepam effect and thus this combination can be given in epileptic patients with other diseases that require treatment by anti-inflammatory drugs

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