Orphenadrine induces secondarily generalized convulsive status epilepticus in rats

The current study was aimed to assess the convulsant potency of orphenadrine (ORPH) in rats together with a screen of different conventional antiepileptic drugs (AEDs) on their efficacy to suppress it. ORPH was administered intraperitoneally (i.p.) in doses of 50-80 mg/kg in male Wistar rats. The latency to first seizure, the number of seizure episodes and the duration of overt status epilepticus (SE) as well as the incidence of deaths was scored with simultaneous electroencephalographic (EEG) recordings. Subsequently, the effects of conventional AEDs on ORPH-evoked (80 mg/kg) seizure incidence were studied. ORPH dose-dependently induced seizures in increasing number of animals, reaching 100% at a dose of 80 mg/kg, associated with low mortality and no drug-related neurotoxicity. Epileptic attacks started as complex partial fits consisting of stereotyped behavior, limb movements, head shaking and myoclonic twitches of the body. Subsequently, an overt generalized convulsive SE appeared, lasting for approximately 2 h. Among conventional AEDs: carbamazepine, ethosuximide and phenytoin had no effect while valproate (p < 0.001), diazepam (p < 0.01), and phenobarbital (p < 0.001) dose-dependently suppressed seizure activity. All the above characteristics make the new model, a useful, easy to perform experimental tool to study the pathophysiology of SE as well as the effects of new AEDs. (C) 2011 Elsevier Inc. All rights reserved.