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Open Access 01-08-2016 | Original Article

Traxoprodil, a selective antagonist of the NR2B subunit of the NMDA receptor, potentiates the antidepressant-like effects of certain antidepressant drugs in the forced swim test in mice

Authors: Ewa Poleszak, Weronika Stasiuk, Aleksandra Szopa, Elżbieta Wyska, Anna Serefko, Anna Oniszczuk, Sylwia Wośko, Katarzyna Świąder, Piotr Wlaź

Published in: Metabolic Brain Disease | Issue 4/2016

Abstract

One of the newest substances, whose antidepressant activity was shown is traxoprodil, which is a selective antagonist of the NR2B subunit of the NMDA receptor. The main goal of the present study was to evaluate the effect of traxoprodil on animals’ behavior using the forced swim test (FST), as well as the effect of traxoprodil (10 mg/kg) on the activity of antidepressants, such as imipramine (15 mg/kg), fluoxetine (5 mg/kg), escitalopram (2 mg/kg) and reboxetine (2.5 mg/kg). Serotonergic lesion and experiment using the selective agonists of serotonin receptors 5-HT_1A and 5-HT₂ was conducted to evaluate the role of the serotonergic system in the antidepressant action of traxoprodil. Brain concentrations of tested agents were determined using HPLC. The results showed that traxoprodil at a dose of 20 and 40 mg/kg exhibited antidepressant activity in the FST and it was not related to changes in animals’ locomotor activity. Co-administration of traxoprodil with imipramine, fluoxetine or escitalopram, each in subtherapeutic doses, significantly affected the animals’ behavior in the FST and, what is important, these changes were not due to the severity of locomotor activity. The observed effect of traxoprodil is only partially associated with serotonergic system and is independent of the effect on the 5-HT_1A and 5-HT₂ serotonin receptors. The results of an attempt to assess the nature of the interaction between traxoprodil and the tested drugs show that in the case of joint administration of traxoprodil and fluoxetine, imipramine or escitalopram, there were interactions in the pharmacokinetic phase.

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Title: Traxoprodil, a selective antagonist of the NR2B subunit of the NMDA receptor, potentiates the antidepressant-like effects of certain antidepressant drugs in the forced swim test in mice
Authors: Ewa Poleszak
Weronika Stasiuk
Aleksandra Szopa
Elżbieta Wyska
Anna Serefko
Anna Oniszczuk
Sylwia Wośko
Katarzyna Świąder
Piotr Wlaź
Publication date: 01-08-2016
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 4/2016
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-016-9810-5

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Traxoprodil, a selective antagonist of the NR2B subunit of the NMDA receptor, potentiates the antidepressant-like effects of certain antidepressant drugs in the forced swim test in mice

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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