Interactions between an antidepressant reboxetine and four classic antiepileptic drugs in the mouse model of myoclonic seizures.
BACKGROUND
The incidence rate of depression among patients with epilepsy is relatively high. The basis of proper therapy is knowledge of drug interactions, which may enable to maximize therapeutic effects and minimize undesired effects of the combined treatment. The purpose of this study was to evaluate the influence of reboxetine, a selective norepinephrine reuptake inhibitor, on the seizure threshold and anticonvulsant effects of four classic antiepileptic drugs: valproate, phenobarbital, ethosuximide, and clonazepam. Moreover, we assessed the adverse effects of reboxetine and combinations of reboxetine with antiepileptic drugs on motor coordination and long-term memory.


METHODS
The subcutaneous pentylenetetrazole (PTZ) test in mice was used to determine effects of anticonvulsant activity of antiepileptic drugs and reboxetine. Undesired effects of either reboxetine or and its combinations with antiepileptics were evaluated in the chimney test (motor coordination) and the step-through passive-avoidance task (long-term memory).


RESULTS
Analysis of obtained results revealed that reboxetine given at doses of 10 and 15 mg/kg doses exhibits anticonvulsant activity expressed by increasing the median convulsive dose (CD(50)) for pentylenetetrazole (p < 0.01). However, the antidepressant did not affect the anticonvulsant action of antiepileptic drugs studied in this seizure model. Moreover, no adverse reactions were found after administration of reboxetine alone or in combinations.


CONCLUSIONS
If further research confirms the obtained results, reboxetine may be categorized as an antidepressant which can be safely administered to epileptic patients treated with valproate, phenobarbital, ethosuximide or clonazepam.
Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Monika
M
Popławska
Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Dorota
D
Wróblewska
Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. Electronic address: kinga.borowicz@umlub.pl.
Kinga K
KK
Borowicz
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004831:Epilepsies, Myoclonic / Q000139:chemically induced / Q000188:drug therapy*; D005013:Ethosuximide / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009025:Morpholines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D009048:Motor Skills / Q000187:drug effects; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000494:pharmacology / Q000627:therapeutic use; D000077593:Reboxetine; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D000928:Antidepressive Agents; D009025:Morpholines; D002998:Clonazepam; D005013:Ethosuximide; D014635:Valproic Acid; D000077593:Reboxetine; D010433:Pentylenetetrazole; D010634:Phenobarbital
Antiepileptic drugs; Depression; Epilepsy; Pentylenetetrazole-induced seizures; Reboxetine