title: New model of pharmacoresistant seizures induced by 3-mercaptopropionic acid in mice.
abstract: About 30% of the patients with epilepsy do not respond to clinically established anticonvulsants, despite having effective concentrations of the antiepileptic drug in plasma. Therefore, new preclinical models of epilepsy are needed to identify more efficacious treatments. We describe here a new drug-resistant seizure model in mice to be used at the early stages of pre-clinical trials. This model consists in inducing daily 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 resistance is strongly associated with the overexpression of P-glycoprotein (Pgp), observed in cerebral cortex, hippocampus and striatum while resistance to Pgp nonsubstrate drugs such as carbamazepine, diazepam and levetiracetam is not observed. This model could be useful for screening novel anticonvulsant drugs with a potential effect on pharmacoresistant seizures treatment.
authors.affiliation: Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina; Instituto de Biología Celular y Neurociencia "Prof. Eduardo De Robertis", Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina. Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: andreaenrique@biol.unlp.edu.ar.
authors.forename: Andrea
authors.initials: A
authors.lastname: Enrique
authors.affiliation: Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Sofía
authors.initials: S
authors.lastname: Goicoechea
authors.affiliation: Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Rocío
authors.initials: R
authors.lastname: Castaño
authors.affiliation: Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Facundo
authors.initials: F
authors.lastname: Taborda
authors.affiliation: Departamento de Farmacobiología, Centro de Investigaciones y Estudios Avanzados, Tlalpan, DF, México.
authors.forename: Luisa
authors.initials: L
authors.lastname: Rocha
authors.affiliation: Unidad de Investigaciones Médicas en Enfermedades Neurológicas, Centro Médico Nacional, Cuauhtémoc, DF, México.
authors.forename: Sandra
authors.initials: S
authors.lastname: Orozco
authors.affiliation: Instituto de Biología Celular y Neurociencia "Prof. Eduardo De Robertis", Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina. Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Elena
authors.initials: E
authors.lastname: Girardi
authors.affiliation: Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Bruno Blanch
mesh_terms: D015097:3-Mercaptopropionic Acid; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011897:Random Allocation; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D010672:Phenytoin; D015097:3-Mercaptopropionic Acid; D010634:Phenobarbital
keywords: 3-Mercaptopropionic acid; Animal models; Drug resistance; Mice; P-glycoprotein; Refractory epilepsy