Monoaminooxidase Inhibitors

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Monoaminooxidase is a complex enzymatic system that is present in practically every organ that catalyzes deamination or inactivation of various natural, biogenic amines, in particular norepinephrine (noradrenaline), epinephrine (adrenaline), and serotonin. Inhibition of MAO increases the quantity of these biogenic amines in nerve endings. MAO inhibitors increase the intercellular concentration of endogenous amines by inhibiting their deamination, which seems to be the cause of their antidepressant action.

These drugs, which form stable complexes with MAO and thereby inhibit its action have long been used in medicine as antidepressants, and are referred to as MAO inhibitors. It is possible, that MAO inhibitors act not by complexation with the enzyme, but by forming covalent bonds that is by irreversibly inactivating the enzyme.

The mechanism of antidepressive action of this series of drugs is likely associated with their inhibition of the oxidizing deamination process of the neurotransmitters norepineph-rine, epinephrine, dopamine, and serotonin, which participate in the transmission of nerve excitement in the CNS. A major drawback of these drugs is the high toxicity associated with their inhibition of not only MAO, but also a number of other nonspecific enzymes.

MAO inhibitors are used in treating severe endogenous, exogenous, and reactive depressions that do not react to treatment with tricyclic antidepressants, as well as for controlling depressive phases in manic-depressive psychoses.

Phenelzine: Phenelzine, 2-phenylethylhydrazine (7.2.1), is synthesized by reacting 2-phenylethylbromide with hydrazine [42-45].

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