Inhibition of N-methyl-D-aspartate receptor function appears to be one of the common actions for antidepressants

In order to explore the possible common action mechanisms of three kinds of classical antidepressants, inhibition of drugs on the N-methyl-D-aspartate (NMOA)-Ca-2-nitric oxide synthase (NOS) signal pathway was observed. With 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Lactic dehydrogenase (LDH) assay, classical antidepressants, desipramine (1, 10 mu M), fluoxetine (0.625-10 mu M) or moclobemide (2.5, 10 mu M) antagonized NMDA 300 mu M induced-lesion in PC12 cells. Using fura-2/AM (acetoxymethyl ester) Labelling assay, desipramine or fluoxetine at doses 1, 5 mu M attenuated the intracellular Ca2+ overload induced by NMOA 200 mu M for 24 h in PC12 cells. Meanwhile, using confocal microscope, it was also found that desipramine 5 mu M, fluoxetine 2.5 mu M or moclobemide 10 mu M decreased the NMDA 20 mu M induced intracellular Ca2+ overload in primarily cultured rat hippocampal neurons. Furthermore, desipramine (1, 5 mu M), fluoxetine (1, 5 mu M) or moclobemide (2.5, 10 mu M) significantly inhibited NOS activity in NMDA (300 mu M) treated PC12 cells for 4 h. In summary, we suggest that inhibition on the function of NMDA-Ca2+-NOS signal pathway appears to be one of the common actions for antidepressants despite their remarkably different structures, which is expected to have great implication for the evaluation and screening in vitro of new antidepressants.