Monoamine oxidase. Its inhibition.

Some 50 years ago the enzyme MAO was discovered by Hare and in the early 1930s Blaschko suggested that MAO may play an important role in the catabolism of monoamines in the central nervous system. With the discovery of iproniazid as an inhibitor of MAO and its introduction as an anti-depressant, many aspects of MAO activity and biogenic amine metabolism in experimental animals and man were examined. Although many other inhibitors of MAO were discovered and used therapeutically as anti-depressants, these drugs fell into disrepute largely because of their side-effects. Furthermore, their anti-depressant properties were questioned. After some years of relative inactivity there is now a revival of interest in the functional role of MAO in the central nervous system and drugs that inhibit or stimulate its activity "specifically". The basic reason for the upsurge of interest is that the enzyme from many tissues, including the brain of animals as well as man, has been purified and characterised. The evidence that neuronal MAO exist with different substrate and inhibitor specificities has led to the suggestion that they have physiological function and that deamination of non-methylated biogenic monoamines can take place in neurons. These findings have led to the advent of new drugs (clorgyline and depranil) with "selective" inhibition of enzyme forms. Their possible usage in the chemotherapy of depressive illness should be considered seriously. Fluctuation in peripheral organs as well as brain MAO is well documented. Recently they have been associated with changes in naturally occurring steroids. Although a decrease in platelet and brain MAO activity has been reported in a number of affect disorders (schizophrenia and bipolar depression) the results of these findings have recently been questioned (20, 141). Obviously further study in this area of research discussed is badly needed.