Development and validation of the maximal electro-shock seizure model in dogs.

Development and validation of the maximal electro-shock seizure model in dogs. Research Abstract Details 

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Development and validation of the maximal electro-shock seizure model in dogs. Abstract Text:

P R Territo,K J Freise,K Newhall,S D Barnhart,S C Peters,D R Engleking,T J Burnett,B Abdul-Karim,H E Shannon,P R Territo,K J Freise,K Newhall,S D Barnhart,S C Peters,D R Engleking,T J Burnett,B Abdul-Karim,H E Shannon,P R Territo,K J Freise,K Newhall,S D Barnhart,S C Peters,D R Engleking,T J Burnett,B Abdul-Karim,H E Shannon,

The development and validation of the maximal electro-shock (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 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 +/- 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 mug/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.

Development and validation of the maximal electro-shock seizure model in dogs. Publishing Authors By Initials

PR Territo,KJ Freise,K Newhall,SD Barnhart,SC Peters,DR Engleking,TJ Burnett,B Abdul-Karim,HE Shannon,PR Territo,KJ Freise,K Newhall,SD Barnhart,SC Peters,DR Engleking,TJ Burnett,B Abdul-Karim,HE Shannon,PR Territo,KJ Freise,K Newhall,SD Barnhart,SC Peters,DR Engleking,TJ Burnett,B Abdul-Karim,HE Shannon,

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Development and validation of the maximal electro-shock seizure model in dogs. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of veterinary pharmacology and therapeutic

VOLUME: 30

Page Numbers: 508-15

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ISSN: 0140-7783

DAY: 9

MONTH: Dec

YEAR: 2007

Development and validation of the maximal electro-shock seizure model in dogs. Information

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LANGUAGE: eng

NlmUniqueID: 7910920

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Grant and Affiliation Information for Development and validation of the maximal electro-shock seizure model in dogs.

AFFILIATION: Lilly Center for Molecular and Anatomical Imaging, Lilly Research Laboratories, A Division(s) of Eli Lilly and Company, Greenfield, IN, USA.

Country: England

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MEDLINETA: J Vet Pharmacol Ther

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