CONTRATADOS
GIRARDI Elena Silvia
congresos y reuniones científicas
Título:
NEW ANTICONVULSANT DRUGS PREVENT P-GLICOPROTEIN (PGP) OVEREXPRESSIÓN IN A PHARMACORESISTANT SEIZURE MODEL IN MICE
Autor/es:
ANDREA ENRIQUE; MAURICIO DI IANNIA, SOFÍA GOICOECHEAA; JUAN JOSE LPEZ, ELENA GIRARDI; ALAN TALEVI
Lugar:
CABA
Reunión:
Congreso; Reunión Conjunta de Sociedades de BioCiencias; 2017
Institución organizadora:
SAFE, SAIB,etc
Resumen:
NEW ANTICONVULSANT DRUGS PREVENT P-GLICOPROTEIN (PGP) OVEREXPRESSIÓN IN A PHARMACORESISTANT SEIZURE MODEL IN MICE.Andrea Enriquea,b, Mauricio Di Iannia, Sofía Goicoecheaa, Juan José Lopezb, Luis Bruno Blancha, Elena Girardib, Alan Taleviaa)Facultad de Ciencias Exactas, Universidad Nacional de La Plata b)Instituto de Biología Celular y Neurociencia "Prof Eduardo De Robertis", UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires. Buenos Aires, ArgentinaAbout 30% of the patients with epilepsy do not respond to clinically established anticonvulsants, despite achieving effective concentrations in plasma. One of the most accepted hypotheses to explain refractory epilepsy is the overexpression of ABC transporters at blood-brain barrier level, which appears to be induced by glutamate through activation of the COX-2 pathway. Here, we have applied ligand-based in silico screening (based on linear discriminant analysis and conformation-independent descriptors) to select compounds from the DrugBank and Sweetlead databases which, according to our computational models, display combined anticonvulsant and anti-inflammatory activity. 5 of the hits from the in silico screening have been assayed in three acute seizure models (MES, PTZ and MP). Those which showed anticonvulsant activity in both MES and PTZ tests without neurotoxic effects but did not in MP test (sebacic acid and γ-decanolactone) were evaluated in a pharmacoresistant seizure model in mice (MP23 model).The MP23 model consists in inducing daily clonic seizures during 23 consecutive days through 3-mercaptopropionic acid (MP) administration. At the end of the treatment, mice are refractory to phenytoin and phenobarbital effects showing an increased P-glycoprotein brain expression. Sebacic acid and γ-decanolactone were administered 30 min before MP administration every day. On day 24 PHT resistance and P-gp expression were studied.All compounds selected by in silico screening showed anticonvulsant activity in at last one of the acute seizure tests. Sebacic acid and γ-decanolactone administration before MP in the MP23 model showed a higher PHT effect in relation to MP alone (p
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