Validation of a Preclinical Drug Screening Platform for Pharmacoresistant Epilepsy
| Autor: | Gerald W. Saunders, Matthew J. Mau, Laura J. Handy, Rizvana Khaleel, Timothy H. Pruess, Jennifer Huff, Karen S. Wilcox, Melissa Barker-Haliski, Zhenmei Lu, Peter J. West, Misty D. Smith, Tristan K. Underwood, Fabiola Vanegas, Peggy Billingsley, Kristina Johnson, Carlos B. Rueda |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug Male medicine.medical_specialty Drug Resistant Epilepsy Neurology media_common.quotation_subject Drug Evaluation Preclinical Pharmacology Bioinformatics Biochemistry Article Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience Epilepsy Mice 0302 clinical medicine Organ Culture Techniques medicine Kindling Neurologic Animals Neurochemistry Pentylenetetrazol Stroke media_common Valproic Acid Electroshock Kainic Acid business.industry Symptomatic seizures General Medicine medicine.disease Rats 030104 developmental biology Anticonvulsants business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurochem Res |
| ISSN: | 1573-6903 |
| Popis: | The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents. It is clear that this traditional screening approach has greatly expanded the number of marketed drugs available to manage the symptomatic seizures associated with epilepsy. In spite of the numerous antiseizure drugs (ASDs) on the market today, the fact remains that nearly 30% of patients are resistant to these currently available medications. To address this unmet medical need, the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) revised its approach to the early evaluation of investigational agents for the treatment of epilepsy in 2015 to include a focus on preclinical approaches to model pharmacoresistant seizures. This present report highlights the in vivo and in vitro findings associated with the initial pharmacological validation of this testing approach using a number of mechanistically diverse, commercially available antiseizure drugs, as well as several probe compounds that are of potential mechanistic interest to the clinical management of epilepsy. |
| Databáze: | OpenAIRE |
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