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.
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-HT1A 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-HT1A 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.
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland. ewa.poleszak@umlub.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Stasiuk
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szopa
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Kraków, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wyska
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Serefko
authors.affiliation: Department of Inorganic Chemistry, Medical University of Lublin, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Oniszczuk
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Wośko
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Świąder
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013550:Swimming; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D005473:Fluoxetine; D015283:Citalopram; C095106:traxoprodil mesylate; D007099:Imipramine
keywords: Antidepressants; Forced swim test; Mice; Pharmacokinetic study; Traxoprodil