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

BACKGROUND: 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. METHODS: 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. RESULTS: Acute treatment with reboxetine (8-16 mg/kg) significantly raised the electroconvulsive threshold. In contrast, chronic reboxetine (2-16 mg/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 (8-12 mg/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. CONCLUSIONS: 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.

Immunological aspects of epilepsy.

In recent years, the concept of an immunological background of some types of epilepsy has been gaining an increasing number of supporters. The following article is an attempt to review the most significant studies that explore irregularities in patients with intractable epilepsy, search for and identify the immunological causal factors of seizures and, finally, associate these factors with particular syndromes that manifest in refractory epilepsy. We also discuss the efficacy of immunomodulatory treatment in the recognized syndromes. Last, we focus on the immunological abnormalities found in patients undergoing antiepileptic therapy with classical antiepileptic drugs as well as changes in the immune system that could be provoked by an epileptic seizure itself.

Acute and chronic treatment with mianserin differentially affects the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock model.

RATIONALE: Epilepsy often coexists with depression. Therefore, the probability of simultaneous treatment with antiepileptics and antidepressants and the possibility of interactions between them are relatively high. OBJECTIVE: The effects of acute and chronic administration of mianserin on the protective activity of valproate (VPA), carbamazepine, phenytoin, and phenobarbital were evaluated in the maximal electroshock in mice. MATERIALS AND METHODS: Animals were subjected to electroconvulsions. Undesired effects were evaluated in the chimney test (motor impairment) and passive-avoidance task (memory deficit). Brain concentrations of antiepileptic drugs were assessed by immunofluorescence. RESULTS: When given acutely, mianserin (at doses greater than or equal to 20 mg/kg) significantly raised the electroconvulsive threshold. The antidepressant, at the subanticonvulsant doses, enhanced the anticonvulsant action of carbamazepine, phenytoin, and VPA. Mianserin administered chronically at 30 mg/kg significantly decreased the electroconvulsive threshold. In contrast to acute treatment, the antidepressant at subeffective doses diminished the anticonvulsant activity of VPA and phenytoin. Mianserin given either acutely or chronically did not affect the brain concentrations of antiepileptic drugs, so a pharmacokinetic contribution to the observed interactions is not probable. Acute and chronic treatment with mianserin and its combinations with antiepileptic drugs did not impair either motor coordination or long-term memory. CONCLUSION: Although acute application of mianserin may potentiate the anticonvulsant action of some antiepileptics, its chronic administration can lead to the opposite effect. Therefore, as far as the presented results can be transferred to clinical conditions, the antidepressant therapy with mianserin should be limited or even avoided in epileptic patients.