Stress detrimentally affects the brain and body and can lead to or be accompanied by depression. Although stress and depression may contribute to each other, the exact molecular mechanism underlying the effects is unclear. However, there is a correlation between stress and an increase in
glucocorticoid secretion which causes a subsequent increase in
monoamine oxidase (
MAO) activity during stress. Consequently,
MAO inhibitors have been used as traditional
antidepressant drugs. Cellular treatment with the synthetic
glucocorticoid,
dexamethasone (a cellular stressor), has been reported to markedly increase both
MAO A and
MAO B catalytic activities, as well as apoptosis. This study compares the neuroprotective abilities of M30 (a new generation inhibitor of both
MAO A and
MAO B) with
rasagiline (
Azilect(®), another new
MAO B inhibitor) and
selegiline (
Deprenyl(®), a traditional
MAO B inhibitor) in the prevention of
dexamethasone-induced brain cell death and
MAO activity in human
neuroblastoma cells, SH-SY5Y. M30 demonstrated the highest inhibitory effect on
MAO A; however, M30 showed the lowest inhibitory effect on
MAO B enzymatic activity in comparison to
rasagiline and
selegiline. Although, M30 exhibited the greatest
neuroprotective effect by decreasing cell death rates and apoptotic DNA damage compared to
rasagiline and
selegiline, these
neuroprotective effects of M30 were, overall, similar to
rasagiline. Summarily, M30 has a generally greater impact on neuroprotection than the
MAO B inhibitors,
selegiline and
rasagiline. Our results suggest that M30 may have great potential in alleviating disorders involving increases in both
MAO A and
MAO B, such as stress-induced disorders.