GIRARDI Elena Silvia
congresos y reuniones científicas
Refractory phenotype reversion by nimodipine administration in a model of epilepsy resistant to phenytoin treatment
GIRARDI ELENA, GONZÁLEZ NN AND LAZAROWSKI ALBERTO
Congreso; 26th International Congress of Epilepsy; 2005
REFRACTORY PHENOTYPE REVERSION BY NIMODIPINE ADMINISTRATION IN A MODEL OF EPILEPSY RESISTANT TO PHENYTOIN TREATMENT Girardi Elena*b , González Nélida N*b and Lazarowski Alberto*a *Instituto de Biología Celular y Neurociencia Prof Dr Eduardo De Robertis. Facultad de Medicina. Universidad de Buenos Aires. Argentina. b CONICET ªDepartamento de Bioquímica Clínica. Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires. Argentina Purpose: As we previously demonstrated, long term treatment with the convulsant drug 3-mercaptopropionic-acid (MP) induce high brain expression of MDR-1 gene, and develop a refractory phenotype to phenytoin (DPH) treatment. The purpose of this work was to study the effect of Nimodipine administration in our model of refractory epilepsy. Methods: Lots of Wistar rats were divided in 5 groups. Groups A,B and C, received a single dose i.p. of MP (45mg/kg) daily injected during 13 days. During the same period, the group D, was daily treated with DPH (50 mg/kg) 30 minutes previous to MP administration. The last treatment day, the group B was treated with DPH 30 minutes previous to MP injection, and the group C, was treated with Nimodipine (2 mg/kg), 30 minute previous to DPH and 60 minute previous to MP administration. As control group, rats were treated with saline (group E). Results: MP induced seizures in Groups A, B and C from the first day. DPH protected from MP-induced convulsions until the third day in group D, however, protective effect was completely lost at day 7. At the thirteenths day, groups A, B and D developed satuts epilepticus (SE). Animal death was observed in groups A, B (100%) and D (50%) Rats with Nimodipine administration (group C), did not develop SE, showed light convulsive episodes, and 100% of them remained alive. Conclusions: Our results suggest that the Nimodipine + DPH can revert the refractory phenotype in MP induced seizures and protect of SE death.