Evaluation of development-specific targets for antiepileptogenic therapy using rapid kindling.
We used the method of rapid hippocampal kindling to assess the potential antiepileptogenic efficacy of a number of anticonvulsant medications. This method afforded a higher throughput than methods based on traditional kindling or post-status epilepticus models of epileptogenesis. This "compressed epileptogenesis" model also permitted the study of age-dependent pharmacologic targets, and distinguished among antiepileptic drugs (AEDs) on the basis of their age-specific antiepileptogenic efficacy. We found retigabine to be the most effective anticonvulsant therapy during early development. Topiramate seemed most effective further along development, whereas some drugs did not demonstrate an age-specific effect. The method also reproduced some of the paradoxical pharmacologic findings previously shown with lamotrigine. Although the utility of this model for screening the antiepileptogenic therapies requires further validation, it introduces the ability to undertake development-specific testing and a more rapid throughput than conventional methods.
Sankar
Raman
R
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. RSankar@ucla.edu
Auvin
Stéphane
S
Kwon
Young Se
YS
Pineda
Eduardo
E
Shin
Don
D
Mazarati
Andréy
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002034:Bumetanide / Q000494:pharmacology / Q000627:therapeutic use; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects*; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D000077236:Topiramate
D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; D000077236:Topiramate; D002034:Bumetanide; C101866:ezogabine; D005632:Fructose