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.