Effective treatments of prolonged status epilepticus in developing rats.

Abstract

We determined the efficacy of diazepam (DZP) and pentobarbital (PTB) in controlling prolonged status epilepticus (SE) in developing rats. One-hour-long SE was induced with kainic acid (KA) or lithium pilocarpine (Li-Pilo) in Postnatal Day 9 (P9), 15 (P15) and 21 (P21) rats, which were then treated with varying doses of DZP (20-60 mg/kg) or PTB (20-60 mg/kg). At P9, neither drug stopped SE, and higher doses could not be used because of high mortality. At P15 and P21, DZP and PTB stopped both behavioral and electrographic SE in a dose-dependent fashion, with similar efficacy in the two seizure models. DZP stopped SE significantly faster than PTB. Administration of a low dose of PTB (20mg/kg) following an initially ineffective treatment with DZP 20mg/kg stopped SE in all rats. The data suggest that high doses of DZP and PTB are needed to stop prolonged SE in developing rats, but their effectiveness is age dependent.