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4 Monoamine Oxidase Inhibitors

Medical treatment of depression is an actual problem of modern society that happens due to the wide-spread occurrence of this disorder in contemporary industrial countries. Monoamine oxidize inhibitors (MAOIs) form a group of antidepressant drugs. Administration and use of MAOIs for depression treatment appears to be contradictory because of the side effects caused by these substances. Thus, MAOIs are used in psychopharmacology rather seldom. This paper discusses the article Monoamine Oxidase Inhibitors: A Modern Guide to an Unrequited Class of Antidepressants and provides necessary information about given chemicals, including probable adverse reactions and their correlation with different types of diets.

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Monoamine oxidase (MOA) exists in two types: A and B form. The activity of MAO-A and MAO-B varies. MAO-A predominantly metabolizes serotonin and norepinephrin (NE), which are basically associated with depression development. MAO-B principally metabolizes phenethylamine, as well as the other trace amines. Metabolizing of dopamine (DA) and thyramine is proper for both MAO-A and MAO-B. The proportion of MAO-A and MAO-B in the brain is 1:3.The main location of MAO-A is in the reticular formation, locus ceruleus of the brainstem and in presynaptic terminals of dopaminergic neurons. MAO-A is also the predominant form of MAO in the tissues and cells of the inner organs except lymphocytes and platelets.

Most of MAOIs which are still used in medicine (tranylcypromine, phenelzine, isocarboxazid) provide irreversible destroying of MAO and nonselective inhibitory activity of both A and B forms of the enzymes. A selective form of MAO-B inhibitor called selegiline shows fewer side effects, but provides amphetamine-like properties. It was revealed that inhibition of MAO-A was effective in depression treatment, but inhibition of MAO-B did not show any antidepressant effect. However, selective inhibition of MAO-B enhances the effect of L-DOPA among the patients with Parkinson's disease. The administration of nonselective MOAIs leads to increasing of DA concentration. This, in turn, helps in treatment of refractory symptoms of diminished positive affect including loss of happiness and energy, decreased self-confidence with depressed mood in the background.

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Patients on MAOIs have to follow low-thyramine diet in order to avoid hypertensive crisis, so-called "cheese reaction" that appears due to the inhibition of intestinal MAO-A with high doses of MAOIs, especially its irreversible forms. Normally, NE, which is released from dietary thyramine, is inactivated by MAO-A in the intestinal tract and cannot be accumulated in blood in enormous quantities which may cause a hypertensive crisis. That is why, all the patients, especially patients with arterial hypertension, should be informed about the necessity of a low-thyramine diet.

The purpose of MAOIs activity investigation is aimed at development of selective reversible MAO-A inhibitors with low side effects and the forms of MAOIs which can be delivered through a skin patch and provide less inhibition of intestinal MAO-A on the background of  nonselective MAO inhibition in the brain.

A problem of drug interactions with MAOIs exists and has to be solved. It predominantly concerns the drugs with adrenergic stimulating effects (e.g. decongestants, including oxymetazoline, pseudoephedrine, etc. which are found in cold medicines and cough suppressants; stimulants, such as amphetamines and methylphenidate; antidepressants with norepinephrine reuptake inhibition (NERI); appetite suppressants and analgesics with NERI and the drugs which inhibit 5-hydrotriptophane (serotonin) uptake. Simultaneous administration of MAO with the drugs producing adrenergic stimulating effect may cause hypertensive crisis. Besides, simultaneous administration of MAO with the drugs which inhibit 5-hydrotriptophane uptake may give rise to serotonin crisis because of increasing of synaptic availability of 5-hydrotriptophane both by MAOIs and agents which block 5-hydrotriptophane (serotonin) reuptake. That leads to enormous hyperthermia due to the impairment of thermoregulation. Signs of serotonin syndrome vary from myoclonus, agitation, migraines at the beginning to the seizures, cardiovascular collapse, malignant hyperthermia, hyperthermic brain impairment and death at the end.

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In conclusion, MAOIs appear to be rather effective measures in treatment of depression and resistant anxiety disorders. However, their administration and use need to be thoroughly controlled both on the part of clinicians and patients in order to get best result without any complications and side effects, such as hypertensive crisis, serotonin syndrome or "cheese reactions".

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