Reboxetine and its influence on the action of classical antiepileptic drugs in the mouse maximal electroshock model

Our previous studies revealed that different classes of antidepressant drugs differently affect seizure phenomena. Continuing our research in this field, in the present study we wanted to investigate the influence of acute and chronic treatment with reboxetine, a selective norepinephrine reuptake inhibitor, on the anticonvulsant action of classical antiepileptic drugs. Experiments were conducted in the model of electroconvulsive threshold and maximal electroshock in mice. Motor coordination was evaluated in the chimney test and long term memory in the step-through passive avoidance task. Brain concentrations of antiepileptic drugs were detected by fluorescence polarization immunoassay. Acute treatment with reboxetine (8–16mg/kg) significantly raised the electroconvulsive threshold. In contrast, chronic reboxetine (2–16mg/kg) did not affect this parameter. Single administration of the antidepressant applied at its subthreshold doses enhanced the action of valproate, carbamazepine and phenobarbital. The antielectroshock effect of phenytoin was also potentiated by acute reboxetine, but only at doses increasing the threshold. Repeated administration of reboxetine (8–12mg/kg) enhanced the anticonvulsant action of carbamazepine, but not that of three remaining antiepileptic drugs. Neither acute nor chronic reboxetine changed the brain concentrations of valproate, carbamazepine, phenytoin or phenobarbital. Therefore, all revealed interactions seem to be pharmacodynamic. In terms of undesired effects, acute/chronic reboxetine and its combinations with classical antiepileptic drugs did not significantly impair motor performance or long-term memory in mice. As far as the obtained data can be extrapolated into clinical conditions, it seems that reboxetine may be safely used in the treatment of depressive disorders in epileptic patients.