of their metabolites in rat brains; tolerance to these effects does not seem to occur with chronic use of moclobemide. Moclobemide lacks anticholinergic effects and cognitive impairments can be improved by moclobemide. Moclobemide suppresses the unstimulated release of certain proinflammatory cytokines which are believed to be involved in the pathophysiology of major depression and stimulates the release of anti-inflammatory cytokines. Long-term treatment with moclobemide leads to an increase in cyclic adenosine monophosphate (cAMP) binding to cAMP-dependent protein kinase (PKA). Moclobemide is chemically unrelated to irreversible MAOI antidepressants and only has a very weak pressor effect of orally administered tyramine. In humans, the n-oxide metabolites of moclobemide and moclobemide itself are the compounds that produce most of the inhibition of MAO-A; other metabolites are significantly less potent than the parent compound. In healthy people moclobemide has a relatively small suppressing effect on REM sleep; in contrast, depressed people who have been treated with moclobemide, progressively show improved sleep over a 4-week period, with an increase in stage 2 non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. There have been conflicting findings with regard to moclobemide altering cortisol levels and whether moclobemide increases growth hormone levels. Testosterone levels increase significantly with long-term use of moclobemide in depressed males. Moclobemide also has neuroprotective properties in its demonstrated anti-hypoxia or anti-ischemia effects; there is a possibility that moclobemide may possess similar neuro-rescuing properties, similar to selegiline, however, research is required to determine this. Moclobemide has also been demonstrated in a single dose research study to possess antinociceptive properties. Platelet MAO is of the MAO-B and this is inhibited only to a small degree in humans; the inhibition is due to low levels of metabolites of moclobemide that have MAO-B inhibiting properties. Moclobemide has been reported to be a mixed MAO-A/MAO-B inhibitor in rats but in man, it has been reported to be a pure MAO-A inhibitor, blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. No reuptake inhibition of any of the neurotransmitters occurs. The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria, fatigue, and difficulties in concentration. The duration and quality of sleep may be improved. In the treatment of depression the antidepressant effect often becomes evident in the first week of therapy (earlier than typically noted with TCAs/SSRIs). MAO inhibition returns completely back to normal after 24 hours, which allows for