cp-101-606 and Depressive-Disorder

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.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Brain; Bupropion; Chromatography, High Pressure Liquid; Cyclopropanes; Depressive Disorder; Desipramine; Disease Models, Animal; Drug Interactions; Excitatory Amino Acid Antagonists; Injections, Intraperitoneal; Male; Mice; Milnacipran; Motor Activity; Paroxetine; Piperidines; Receptors, N-Methyl-D-Aspartate

The main objective of our study was to evaluate the influence of traxoprodil on the activity of the atypical antidepressant drugs (agomelatine, mianserin, tianeptine).. 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.. Concurrent intraperitoneal administration of per se ineffective doses of traxoprodil (10mg/kg) and agomelatine (20mg/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 (10mg/kg) or tianeptine (15mg/kg).. 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.

Topics: Acetamides; Animals; Antidepressive Agents; Brain; Depression; Depressive Disorder; Drug Synergism; Male; Mianserin; Mice; Motor Activity; Piperidines; Swimming; Thiazepines