Striking differences in individual anticonvulsant response to phenobarbital in rats with spontaneous seizures after status epilepticus.

摘要: Summary: Purpose: More than one third of patients with epilepsy have inadequate control seizures drug therapy, but mechanisms intractability are largely unknown. Because this large number pharmacoresistant epilepsy, the existing process antiepileptic (AED) discovery and development must be reevaluated a focus on preclinical models therapy-resistant syndromes such as mesial temporal lobe (TLE). However, although various rodent TLE available, pharmacoresponsiveness most is not well known. In present study, we used post–status epilepticus model to examine whether rats spontaneous recurrent (SRSs) differ in their individual responses phenobarbital (PB). Methods: Status was induced Sprague–Dawley by prolonged electrical stimulation basolateral amygdala. Once had developed SRSs, seizure frequency severity were determined continuous EEG/video recording over 6-week period (i.e., predrug 2 weeks, followed PB treatment for postdrug weeks). administered twice daily at maximal tolerated doses. Results: Analysis plasma concentrations showed that within therapeutic range (10–40 μg/ml) maintained all throughout treatment. six (55%) 11 rats, complete achieved, another rat exhibited >90% reduction frequency. These seven considered responders. The remaining four (36%) either no response (n = 3) or only moderate therefore nonresponders. Plasma did between these two groups rats. Conclusions: data demonstrate that, similar SRSs markedly AED Pharmacoresistant selected from may provide unique study pharmacoresistance identify novel AEDs treating currently controlled therapies.