Moclobemide Norepinephrine

Therapeutic efficacy by selective MAO-A inhibitors (such as clorgyline or moclobemide) in major depressions strongly suggests that MAO inhibition at central serotonin or norepinephrine synapses or both is responsible for the antidepressant properties of these agents. However, since complete MAO-A inhibition is achieved clinically within a few days of treatment, while the antidepressant effects of these drugs are not observed for 2 to 3 weeks, suggests that additional actions must be involved. 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

Inhibitors of MAO (A) block enzyme located in mitochondria, which serves to scavenge axoplasmic free norepinephrine (NE). Inhibition of the enzyme causes free NE concentrations to rise. Likewise, dopamine catabolism is impaired, making more of it available for NE synthesis. In the CNS, inhibition of MAO affects neuronal storage not only of NE but also of dopamine and serotonin. The functional sequelae of these changes include a general increase in psychomotor drive (thymeretic effect) and mood elevation (A). Moclobemide reversibly inhibits MAOa and is used as an antidepressant. The MAOB inhibitor selegiline (deprenyl) retards the catabolism of dopamine, an effect used in the treatment of Parkinsonism (p. 188). 

Inhibitors of monoamine oxidase A (thy-meretics). Moclobemide is the only representative of this group. It produces a reversible inhibition of MAOa, which is responsible for inactivation of the amines norepinephrine, dopamine, and serotonin (A). Enzyme inhibition results in an increased concentration of these neurotransmitters in the synaptic cleft. Moclobemide is less effective as an antidepressant than as a psychomotor stimulant. It is indicated only in depressions with extreme psychomotor slowing and is contraindicated in patients at risk of suicide. 

MAOIs MIRTAZAPINE Risk of severe hypertensive reactions and of serotonin syndrome > For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome Additive inhibition of both serotonin and norepinephrine reuptake Avoid co-administration. MAOIs should not be started for at least 2 weeks after stopping mirtazapine (moclobemide can be started at least 1 week after stopping mirtazapine). Conversely, mirtazapine should not be started for at least 2 weeks after stopping MAOIs... 

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