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Combination of valproate and paroxetine in mice exposed to picrotoxin.

Kamal SM - Int J Nanomedicine (2012)

Bottom Line: However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations.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.These results favor their application in management of epilepsy-depression comorbidities.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of Ain-Shams, Cairo, Egypt. saharkamal2003@hotmail.com

ABSTRACT
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.

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Related in: MedlinePlus

Effect of tested drugs on the gamma aminobutyric acid (GABA) level in the nucleus accumbens of tested mice.Note: Sodium valproate significantly (P < 0.05) increased the GABA concentration in the nucleus accumbens of mice of group 2 compared with group 1. GABA concentration of chronic mild stress mice was significantly increased (P < 0.05) by both sodium valproate and paroxetine compared with all tested groups. *P < 0.05 significant increase compared with groups 1 and 3.
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f2-ijn-7-2583: Effect of tested drugs on the gamma aminobutyric acid (GABA) level in the nucleus accumbens of tested mice.Note: Sodium valproate significantly (P < 0.05) increased the GABA concentration in the nucleus accumbens of mice of group 2 compared with group 1. GABA concentration of chronic mild stress mice was significantly increased (P < 0.05) by both sodium valproate and paroxetine compared with all tested groups. *P < 0.05 significant increase compared with groups 1 and 3.

Mentions: Sodium valproate administration to group 2 significantly (P < 0.05) increased GABA level compared with the control group. Coadministration of paroxetine with sodium valproate significantly (P < 0.05) increased GABA level if compared with the control, sodium valproate, or paroxetine groups (Figure 2).


Combination of valproate and paroxetine in mice exposed to picrotoxin.

Kamal SM - Int J Nanomedicine (2012)

Effect of tested drugs on the gamma aminobutyric acid (GABA) level in the nucleus accumbens of tested mice.Note: Sodium valproate significantly (P < 0.05) increased the GABA concentration in the nucleus accumbens of mice of group 2 compared with group 1. GABA concentration of chronic mild stress mice was significantly increased (P < 0.05) by both sodium valproate and paroxetine compared with all tested groups. *P < 0.05 significant increase compared with groups 1 and 3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367497&req=5

f2-ijn-7-2583: Effect of tested drugs on the gamma aminobutyric acid (GABA) level in the nucleus accumbens of tested mice.Note: Sodium valproate significantly (P < 0.05) increased the GABA concentration in the nucleus accumbens of mice of group 2 compared with group 1. GABA concentration of chronic mild stress mice was significantly increased (P < 0.05) by both sodium valproate and paroxetine compared with all tested groups. *P < 0.05 significant increase compared with groups 1 and 3.
Mentions: Sodium valproate administration to group 2 significantly (P < 0.05) increased GABA level compared with the control group. Coadministration of paroxetine with sodium valproate significantly (P < 0.05) increased GABA level if compared with the control, sodium valproate, or paroxetine groups (Figure 2).

Bottom Line: However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations.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.These results favor their application in management of epilepsy-depression comorbidities.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of Ain-Shams, Cairo, Egypt. saharkamal2003@hotmail.com

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus