New model of pharmacoresistant seizures induced by3-mercaptopropionic acid in mice

ELENA GIRARDI; LUIS BRUNO BLANCH; ANDREA ENRIQUE, SOFÍA GOICOECHEA, FACUNDO TABORDA, ROCÍO CASTAÑO; LUISA ROCHA,SANDRA OROSCO ; ELENA GIRARDI; LUIS BRUNO BLANCH; ANDREA ENRIQUE, SOFÍA GOICOECHEA, FACUNDO TABORDA, ROCÍO CASTAÑO; LUISA ROCHA,SANDRA OROSCO

EPILEPSY RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 129 p. 8 - 16

0920-1211

About 30% of the patients with epilepsy do not respond to clinically established anticonvulsants, despitehaving effective concentrations of the antiepileptic drug in plasma. Therefore, new preclinical modelsof epilepsy are needed to identify more efficacious treatments. We describe here a new drug-resistantseizure model in mice to be used at the early stages of pre-clinical trials. This model consists in inducingdaily generalized seizures for 23 consecutive days by administration of 3-mercaptopropionic acid (MP).As a result, 100% of animals become resistant to phenytoin and 80% to phenobarbital. Such resistanceis strongly associated with the overexpression of P-glycoprotein (Pgp), observed in cerebral cortex, hip-pocampus and striatum while resistance to Pgp nonsubstrate drugs such as carbamazepine, diazepamand levetiracetam is not observed.This model could be useful for screening novel anticonvulsant drugs with a potential effect on phar-macoresistant seizures treatment.