Monoamine oxidase inhibitor

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.

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. 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 deprenyl and moclobemide provides a safer alternative, although not always as effective as the old types. Additionally, studies suggest that the recommended dosage range for moclobemide (300-600mg) should be revised to 450mg-1200mg in major depression.

Transdermal delivery of deprenyl (20mg/day) has been tested, and the product is expected to be generally available some time in 2005. No dietary interactions have been observed with transdermal delivery, as intestinal MAO is not affected to a significant degree. The incidence of side effects was lower than that for placebo in all other categories than skin irritation at the application site (comparable to nicotine patches, about 1 in 3).

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 and noradrenaline. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.

MAOIs can potentiate the action of a number of other drugs, such as opiates, ephedrine, adrenaline, etc.

When ingested orally, they also inhibit the catabolism of dietary amines. Sufficient intestinal MAO-A inhibition can lead to hypertensive crises when foods containing tyramine are consumed, or hyperserotonemia if foods containing tryptophan are consumed. 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). Examples of trytophan-containing foods include bananas and nuts. Examples of levodopa-containing foods include broad beans.

Tobacco and Harmal contain harmala, which is an inhibitor of MAO-B, a serotonin antagonist and CNS stimulant. Long-term smokers usually have only 40-60% of normal MAO-B activity.

Combined use of non-selective MAO inhibitors or MAO-A inhibitors and serotonergic drugs is likely to lead to serotonin syndrome.

MAOIs, often in the form of harmal, are also sometimes used with hallucinogenic drugs, many of which are potentiated. Ayahuasca (Banisteriopsis caapi, containing harmala, combined with a DMT admixture such as Psychotria viridis) is the most common such combination. The effects of LSD appear to be diminished or abolished by MAO-A inhibition.

Monoamine oxidase inhibitors include:

• Isocarboxazid (Marplan)
• Moclobemide (Aurorix, Manerix, Moclodura®)
• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Deprenyl (Selegiline, Eldepryl)
• Harmala (present in Harmal, Banisteriopsis caapi, and tobacco; also acts as a serotonin antagonist and CNS stimulant).de:Monoaminooxidase-Hemmer

fr:IMAO he:מונואמין אוקסידאז pl:Inhibitory monoaminooksydazy pt:Antidepressor inibidor da MAO