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In the largest studies to date in veterinary medicine, the mortality rate was 25.3�C38.5%.[6, 7] In humans, SE-associated mortality estimates typically range http://www.selleck.cn/products/incb024360.html from 3 to 40%,[8] depending on the population evaluated, but overall mortality is approximately 22%,[9] similar to that seen in dogs. The optimal treatment for SE in humans and dogs is unknown. Despite the large number of cases, few well-controlled studies have been performed evaluating the efficacy of available medications in humans.[10-12] To our knowledge, no published studies exist in dogs. An injectable formulation of levetiracetam1 (LEV) was approved in 2006 for use as bridge therapy in patients unable to take oral medications. Since then, its off-label use in humans has been http://www.selleckchem.com/products/bmn-673.html reported[13, 14] as has its use in dogs for the treatment of refractory SE, but no prospective, blinded studies have been conducted. The mechanism of action of LEV is not completely understood, but it is thought to act by binding to the synaptic vesicle 2a protein on the presynaptic terminal, and modulating synaptic vesicle fusion and neurotransmitter release.[15, 16] There are a number of other purported mechanisms that may inhibit epileptic activity, including indirect effects on GABAergic neurotransmission, inhibiting the Na+-dependent Cl?/HCO3? exchanger, and modulation of K+ and high-voltage Ca2+ channels.[17] LEV has a favorable pharmacokinetic profile. It is relatively rapidly and extensively absorbed via PO and IM routes; readily crosses the blood-brain barrier; is minimally protein-bound ( http://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html short plasma half-life of 3�C4?hours.[18, 19] However, in rats, LEV half-life in the brain and cerebrospinal fluid (CSF) is 1.5�C2 times longer than the plasma half-life, and it is thought to maintain higher concentrations in the brain in humans.[20, 21] The primary aim of this pilot study was to evaluate the efficacy and safety of IV LEV compared with placebo in client-owned dogs with SE or ARS. We hypothesized that LEV treatment would be superior to placebo in stopping seizure activity in dogs with SE or ARS after treatment with IV diazepam. Nineteen client-owned dogs with SE or ARS presented to the Veterinary Medical Center (VMC) of the University of Minnesota (UMN) between October 2007 and March 2010 were included in the study. This study was approved by the UMN Institutional Animal Care and Use Committee (#0905A65361). Informed consent was obtained from all owners before enrollment in the study.