Traxoprodil augments the antidepressant-like activity of agomelatine but not of mianserin or tianeptine in the forced swim test in mice

Background: The main objective of our study was to evaluate the influence of traxoprodil on the activity of the atypical antidepressant drugs (agomelatine, mianserin, tianeptine). Methods: The forced swim test (FST) in mice was used to determine the antidepressant-like activity of the tested agents. Drugs levels in brain tissue were assessed by a high performance liquid chromatography method. Results: Concurrent intraperitoneal administration of per se ineffective doses of traxoprodil (10 mg/kg) and agomelatine (20 mg/kg) shortened the immobility time of animals in the FST. The observed effect was associated with elevated brain levels of traxoprodil. Similar interaction was not detected for traxoprodil and mianserin (10 mg/kg) or tianeptine (15 mg/kg). Conclusion: Traxoprodil-agomelatine interaction is pharmacokinetic in nature. A combination of these agents has a potential to become an interesting strategy in the treatment of depression. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.