Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models.
Chronic electrical stimulation via corneal electrodes can rapidly yield large numbers of kindled mice with a seizure phenotype reflective of secondarily generalized partial seizures. The corneal kindled mouse model has been found to be a highly sensitive and efficient screening model for antiepileptic drug (AED) discovery. The present study further evaluates the utility of the corneal kindled mouse model as a tool for rapid screening of investigational AEDs. Results obtained with nine AEDs (valproic acid, lamotrigine, phenytoin, carbamazepine, levetiracetam, vigabatrin, topiramate, tiagabine, and ezogabine) with varying mechanisms of action and clinical spectrums, as well as six investigational compounds were evaluated in the corneal kindled mouse. ED(50) values are compared to those obtained in the hippocampal kindled rat, the mouse maximal electroshock (MES) model, the 6Hz partial psychomotor seizure model, and the subcutaneous pentylenetetrazol (scPTZ) test. The results obtained in the corneal kindled mouse demonstrate a positive correlation with those attained employing established preclinical models: MES (r² = 0.9511), scPTZ (r² = 0.9697), 6Hz (r² = 0.9519), and hippocampal kindling (r² = 0.9037). The demonstrated predictive ability of the corneal kindled mouse model supports its use in the early evaluation of investigational AEDs.
Rowley
Nicole M
NM
Anticonvulsant Drug Development Program, Department of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT 84108, USA.
White
H Steve
HS
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001703:Biophysics; D003315:Cornea / Q000294:innervation*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004558:Electric Stimulation / Q000009:adverse effects; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009900:Optic Nerve / Q000503:physiopathology; D010433:Pentylenetetrazole / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D013997:Time Factors
D000927:Anticonvulsants; D010433:Pentylenetetrazole