Combination of valproate and paroxetine in mice exposed to picrotoxin

The frequent coexistence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with antiepileptic drugs in the management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present st...

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Bibliographic Details
Published in:International journal of nanomedicine 2012-01, Vol.7 (default), p.2583-2589
Main Author: Kamal, Sahar M
Format: Article
Language:English
Subjects:
albino mice
Animals
Anticonvulsants - pharmacology
Antidepressants
Brain Chemistry - drug effects
Convulsions & seizures
Drug Combinations
GABA
gamma-Aminobutyric Acid - metabolism
Mice
nucleus accumbens
Nucleus Accumbens - chemistry
Nucleus Accumbens - drug effects
Nucleus Accumbens - metabolism
Original Research
paroxetine
Paroxetine - pharmacology
Picrotoxin
Seizures - chemically induced
Seizures - metabolism
Seizures - therapy
Serotonin Uptake Inhibitors - pharmacology
Thiobarbituric Acid Reactive Substances - metabolism
valproate
Valproic Acid - pharmacology
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Summary:The frequent coexistence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with antiepileptic drugs in the management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present study investigates the effect of the antidepressant paroxetine (a selective serotonin reuptake inhibitor) administered alone or in combination with the antiepileptic drug sodium valproate on chemoconvulsions induced by picrotoxin (PTX). Seizure score was recorded in vivo, and the levels of thiobarbituric acid-reactive substances and gamma aminobutyric acid (GABA) were measured in the nucleus accumbens of the tested groups of mice. The results show enhancement of seizure severity with significant reduction in GABA levels upon PTX treatment that were reversed by its combination with sodium valproate. On the other hand, paroxetine administered in combination with sodium valproate provided significant protection against PTX-induced convulsions as well as a significant increase in GABA levels in selected brain areas. These results favor their application in management of epilepsy-depression comorbidities.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S31050