title: Influence of the selective antagonist of the NR2B subunit of the NMDA receptor, traxoprodil, on the antidepressant-like activity of desipramine, paroxetine, milnacipran, and bupropion in mice.
abstract: Pre-clinical and clinical studies indicated that a blockade of the NMDA receptor complex creates new opportunities for the treatment of affective disorders, including depression. The aim of the present study was to assess the influence of traxoprodil (10 mg/kg) on the activity of desipramine (10 mg/kg), paroxetine (0.5 mg/kg), milnacipran (1.25 mg/kg), and bupropion (10 mg/kg), each at sub-therapeutic doses. Moreover, brain levels of traxoprodil and tested agents were determined using HPLC. The obtained results were used to ascertain the nature of occurring interaction between traxoprodil and studied antidepressants. The experiment was carried out on naïve adult male Albino Swiss mice. Traxoprodil and other tested drugs were administered intraperitoneally. The influence of traxoprodil on the activity of selected antidepressants was evaluated in forced swim test (FST). Locomotor activity was estimated to exclude false positive/negative data. To assess the influence of traxoprodil on the concentration of used antidepressants, their levels were determined in murine brains using HPLC. Results indicated that traxoprodil potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity. Only in the case of co-administration of traxoprodil and bupropion, increased bupropion concentrations in brain tissue were observed. All tested agents increased the traxoprodil levels in the brain. Administration of a sub-active dose of traxoprodil with antidepressants from different chemical groups, which act via enhancing monoaminergic transduction, caused the antidepressant-like effect in FST in mice. The interactions of traxoprodil with desipramine, paroxetine, milnacipran, and bupropion occur, at least partially, in the pharmacokinetic phase.
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, PL-20080, Lublin, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Stasiuk
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL-20093, Lublin, Poland. aleksandra.szopa@umlub.pl.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szopa
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL-20093, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Serefko
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Medyczna 9, PL-30688, Kraków, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wyska
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL-20093, Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Świąder
authors.affiliation: Department of Toxicology, Medical University of Lublin, Chodźki 8, PL-20093, Lublin, Poland.|Independent Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, PL-20950, Lublin, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Dudka
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL-20033, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL-20093, Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016642:Bupropion / Q000493:pharmacokinetics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes / Q000493:pharmacokinetics / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D003891:Desipramine / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D000078764:Milnacipran; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000493:pharmacokinetics / Q000494:pharmacology; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000928:Antidepressive Agents; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016642:Bupropion; D017374:Paroxetine; C095106:traxoprodil mesylate; D000078764:Milnacipran; D003891:Desipramine
keywords: Antidepressants; Forced swim test; Mice; NMDA receptor ligand; Pharmacokinetic study; Traxoprodil