{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T05:40:15Z","timestamp":1697348415734},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,10,22]],"date-time":"2007-10-22T00:00:00Z","timestamp":1193011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>The development and validation of the maximal electro\u2010shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300\u2003mA, 200\u2003msec) animals underwent clonic\u2010tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5\u2003\u00b1\u200324.4\u2003sec (<jats:italic>n<\/jats:italic>\u2003=\u20038). Pretreatment of animals with Pb at 3, 10, and 30\u2003mg\/kg, in a 4\u2010by\u20104 complete block crossover design (Latin\u2010Square), resulted in a dose\u2010dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose\u2010dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS\u2003=\u20031 was approximately 11.4\u2003mg\/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS\u2003=\u20031 occurs at plasma Pb concentration of approximately 16.0\u2003\u03bcg\/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds.<\/jats:p>","DOI":"10.1111\/j.1365-2885.2007.00906.x","type":"journal-article","created":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T05:53:45Z","timestamp":1193205225000},"page":"508-515","source":"Crossref","is-referenced-by-count":5,"title":["Development and validation of the maximal electro\u2010shock seizure model in dogs"],"prefix":"10.1111","volume":"30","author":[{"given":"P. R.","family":"TERRITO","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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