Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. Due to potentially serious dietary and drug interactions they are used less frequently than other classes of antidepressant drugs (for example tricyclic antidepressants and selective serotonin reuptake inhibitors). However, in some cases where patients are unresponsive to other treatments they are tried, often with a marked success. They are particularly effective in treating atypical depression, and have shown efficacy in helping smokers to quit.

Therapeutical use
In the past they were prescribed for those resistant to tricyclic antidepressant therapy, but newer MAOIs are now sometimes used as first-line therapy. They are also used for treating agoraphobia and social anxiety. MAOIs, in their original form presented an unusual problem for the prescribing physician. If a physician was prescribing MAOIs for depression, he/she had to take into consideration the fact that he/she was offering the patient a ready, though unpleasant, route to suicide. Currently, the availability of Selegiline and moclobemide provides a safer alternative, although not always as effective as the old types.

Traditional and entheogenic use
MAOIs can be used to potentiate the effect of a number of hallucinogenic drugs, notably phenethylamines, tryptamines, DXM and several others.

Ayahuasca, an entheogenic brew traditionally used in strict ritual context by South American indians, is a mixture of Banisteriopsis caapi, a vine containing various harmala alkaloids, and another plant containing N,N-DMT or 5-MeO-DMT alkaloids, usually Psychotria viridis or Diplopterys cabrerana. Modern, western analogues to ayahuasca often substitute Syrian Rue for B. caapi and Mimosa hostilis as a DMT source. As DMT is inactive orally on its own, it must be combined with MAOI when taken orally.

Mode of action
MAOIs act by inhibiting the activity of monoamine oxidase preventing the breakdown of monoamine neurotransmitters and so increasing the available stores. There are two isoforms, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, adrenaline and noradrenaline. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.

Reversibility
The early MAOIs inhibited monoamine oxidase irreversibly. When they react with monoamine oxidase, they permanently deactivate it, and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. A few newer MAOIs, notably moclobemide, are reversible, meaning that they can inhibit the enzyme for a time, but eventually detach, allowing the enzyme to function once more.

Selectivity
In addition to reversibility, MAOIs differ by their selectivity of the MAO receptor. Older MAOIs inhibit both MAO-A and MAO-B equally, but newer MAOIs have been developed that target one over the other. For example, a 300 mg dose of moclobemide (Manerix, Aurorix) causes 80% inhibition of MAO-A and 20-30% inhibition of MAO-B.

Dangers
When ingested orally, MAOIs inhibit the catabolism of dietary amines. Sufficient intestinal MAO-A inhibition can lead to hypertensive crisis (noradrenergic syndrome), when foods containing tyramine are consumed, or hyperserotonemia if foods containing tryptophan are consumed. Tyramine is a building block of norepinephrine. MAOIs inhibit MAO so that it can't get rid of excess norepinephrine. Excessive amounts of norepinephrine can lead to a hypertensive crisis and can even cause intracerebral hemorrhage and death after consumption of certain tyarmine-containing foods or drinks. Hypertensive crises can sometimes result in stroke or cardiac arrythmia if not treated. This risk is not present with RIMAs. Both kinds of intestinal MAO-inhbition can cause hyperpyrexia if levodopa-containing foods are consumed.

Examples of foods with high levels of tyramine include liver, Chianti and other aged wines, aged cheeses, meat extracts (e.g. Bovril) and yeast extracts (e.g. Marmite, Vegemite). A separate list of foods containing tyramine has been established. Examples of levodopa-containing foods include broad beans.

Although the "MAOI diet" is not necessary for those taking selective MAO-B inhibitors. Since the selective MAOIs are not 100% selective, taking a drug metabolized by MAO-B will still be potentially dangerous while taking a selective MAO-A inhibitor, and vice versa.

Combined use of non-selective MAO inhibitors or MAO-A inhibitors and serotonergic drugs, such as SSRIs or MDMA and other phenylethylamines, is likely to lead to serotonin syndrome. Serotonin syndrom can also occur, when combining MAOIs with certain anesthetics as meperidine. However, other anesthetics as morphine and codeine have been used safely with MAOIs.

MAOIs may not be combined with other anti-depressants, most notably tricyclic antidepressants, as the combined use may result in hypertensive crisis.

List of MAOIs
Monoamine oxidase inhibitors include:


 * Isocarboxazid (Marplan)
 * Moclobemide (Aurorix, Manerix, Moclodura&reg;)
 * Phenelzine (Nardil)
 * Tranylcypromine (Parnate)
 * Selegiline (Selegiline, Eldepryl)
 * Harmala (present in Harmal, Banisteriopsis caapi, and tobacco).
 * Certain tryptamines such 5-MeO-DMT or 5-MeO-AMT are weak MAOIs

Monoaminooxidase-Hemmer IMAO & Monoamino-oxidaseremmer Inhibitory monoaminooksydazy Antidepressor inibidor da MAO