A picture of 150 mg tablets of the reversible MAOI drug<unk> , brand name Aurorix.<unk>  is a benzamide, derivative of morpholine, which acts pharmacologically as a selective, reversible inhibitor of monoamine oxidase-A (RIMA), a type of monoamine oxidase inhibitor (MAOI), and increases levels of norepinephrine (noradrenaline), dopamine, and especially serotonin in neuronal cells as well as in synaptic vesicles; extracellular levels also increase which results in increased monoamine receptor stimulation and suppression of REM sleep, down regulation of Beta-3 adrenergic receptors. A single 300 mg dose of<unk>  inhibits 80% of monoamine oxidase-A (MAO-A) and 30% of monoamine oxidase-B (MAO-B), blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. There is also some evidence of<unk>  possessing neuroprotective properties in rodent models. There is no cumulative effect of<unk>  centrally when taken long-term. With long-term use of<unk> , there is a significant down-regulation of B-adrenoceptors. Single or repeated dosing with 100–300 mg of<unk>  leads to a reduction in deaminated metabolites of amines such as 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethylglycol as well as 5-HIAA. Excretion of homovanillic acid and vanillylmandelic acid via urine is also reduced. There is also a temporary increase in prolactin during initial intake of 100–300 mg of<unk> . L-dihydroxyphenylalanine is also reduced. Inhibition of the serotonin metabolite is less pronounced than the norepinephrine metabolite which suggests there are other major metabolic pathways for serotonin other than MAO-A. It has been described as a 'slow binding inhibitor', whereby conformational changes to either<unk>  or the enzyme to MAO-A slowly form a more tightly bound complex, resulting in the non-competitive MAO inhibition by<unk> . With three times daily dosing the inhibition on MAO-A was relatively constant with<unk> . The MAO inhibition of<unk>  lasts about 8–10 hours and wears off completely by 24 hours after dosing. The inhibition of MAO-A by<unk>  is 10 times more potent than the irreversible MAOIs phenelzine and approximately equivalent to tranylcypromine and isocarboxazid.<unk>  increases levels of extracellular monoamines and decreases levels of their metabolites in rat brains; tolerance to these effects does not seem to occur with chronic use of<unk> .<unk>  lacks anticholinergic effects and cognitive impairments can be improved by<unk> .<unk>  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<unk>  leads to an increase in cyclic adenosine monophosphate (cAMP) binding to cAMP-dependent protein kinase (PKA).<unk>  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<unk>  and<unk>  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<unk>  has a relatively small suppressing effect on REM sleep; in contrast, depressed people who have been treated with<unk> , 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<unk>  altering cortisol levels and whether<unk>  increases growth hormone levels. Testosterone levels increase significantly with long-term use of<unk>  in depressed males.<unk>  also has neuroprotective properties in its demonstrated anti-hypoxia or anti-ischemia effects; there is a possibility that<unk>  may possess similar neuro-rescuing properties, similar to selegiline, however, research is required to determine this.<unk>  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<unk>  that have MAO-B inhibiting properties.<unk>  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 changing to another antidepressant within 24 hours of the last dose taken of<unk> .
Moclobemide
Torasemide
Altretamine
Bumetanide
Yohimbine
Brimonidine
Clonidine
Amiloride