DIARYLETHYLAMINE METHOXPHENIDINE AND ITS POTENTIAL THERAPEUTIC BENEFIT FOR THE THERAPY OF TREATMENT-RESISTANT DEPRESSION

NMDA receptor (NMDAR) antagonists represent a promising yet incompletely understood class of compounds with potential application in the treatment of depression, particularly in patients with treatment-resistant depression. Although some NMDAR antagonists exhibit rapid antidepressant effects, their clinical use is often limited by psychotomimetic and other behavioral side effects.
The aim of this study is to characterize behavioral changes in a preclinical model of depression and to assess the antidepressant and psychotomimetic profile of the NMDAR antagonist methoxphenidine (MXP). Experiments are conducted in laboratory rats divided into a non-operated control group and a group subjected to olfactory bulbectomy, an established model of a depression-like phenotype. MXP is administered at doses of 1 and 10 mg/kg to evaluate potential antidepressant effects and to determine the presence of undesirable psychotomimetic behavioral manifestations.
Control animals are assessed using the open field and prepulse inhibition tests, while bulbectomized animals undergo a comprehensive behavioral test battery including the open field, elevated plus maze, anhedonia test, and Morris water maze.
The obtained data will contribute to the assessment of the relevance of the olfactory bulbectomy model for studying behavioral consequences of NMDAR antagonism and will provide an experimental basis for further investigation of the antidepressant potential of MXP.