How do the MAO inhibitors increase the levels of norepinephrine and serotonin in the brain?

Question

How do the MAO inhibitors increase the levels of norepinephrine and serotonin in the brain?

Answer 1

MAOIs are among the most potent, scary and useful drugs for depression. Basically it goes like this.

There is an enzyme in your body called MAO- Or Monoamine Oxidase. It does exactly what it sounds, breaks down monoamine molecules. This includes serotonin, norepinephrine and dopamine. This enzyme is distributed throughout the body, but the important places are the liver and the nervous system.

In the nervous system, MAO acts as the end of the lifecycle for a neurotransmitter of the above types. It grabs them and breaks them down into inactive metabolites. Traditional MAOI drugs react with this enzyme as a 'suicide' substrate. The MAO enzyme becomes stuck to the MAOI drug and useless. By decreasing the amount of MAO available in nerve cells, fewer neurotransmitters are broken down, increasing availability. There are variations on this - reversible rather than suicide substrates, or ones that selectively target different forms of the enzyme.

Most of the danger arises from MAOI action in the liver. The liver is responsible for breaking down anything nasty or unpleasant in the food, in this case usually Tyramine. Tyramine can cause the hypertensive crisis associated with MAOI use and foods containing it.

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