Monoamine oxidase and inhibitors.

TLDR: The correlation of increasing amines in the brain and the antidepressive effect of the monoamine oxidase inhibitors or tricyclic antidepressants is not confirmed, but it is possible that the difficulties in carrying out successful therapy with antidepressant drugs may be caused by unknown hereditary factors concerning response to psyehotropie drugs.

Abstract: The monoamine oxidase localized in the mitochondria metabolises the catecholamines in the central nervous system by oxidative desamination. The most important function of the monoamine oxidase is the intracellular regulation of the levels of norepinephrine and 5-hydroxytryptamine. In the ncurones the amines are protected by granula from the enzymatic activity of the monoamine oxidase. There is an active ATP-dependent storagemechanism preventing the amines from diffusion to the region of enzymatic destruction. By this intracellular mechanism the concentration of the amines in the storing granula is controlled. By inhibiting the monoamine oxidase by a specific inhibitor, for instance iproniazid, the concentration of the catccholamines in the granula may be increased. However, the stored amines are probably localized in two or more different pools; one in the inner region of the cell and the other one near the synaptic nerveendings. The released amines of the inner pool are quickly inactivated by the monoamine oxidase. The amines released by the inner pool reach the synapses in their active form, or are inactivated by the o-methyltransferase, for instance after stimulation of the sympathetic neurones. The first reaction after inhibiting the monoamine oxidase may be an accumulation of amines in the inner region of the cell. I t may be possible that there is also an increase of the amines in the granula near the surface of the cell, because there is probably a steady state between the various different pools of amines. The increase of free sympathieomimetic amines in the region of the nerve synapses could be responsible for the antidepressive effect. However, we cannot decide whether there is an unspecific psyehotropic stimulation by the free amines or a compensation of an abnormal metabolic pathway responsible for the depressive effects. The correlation of increasing amines in the brain and the antidepressive effect of the monoamine oxidase inhibitors or tricyclic antidepressants is not confirmed up to now by exact experiments, especially concerning the group of tricyclie antidepressants which interfere in a direct manner with phosphorylation, the metabolism of glucose and lipids as well as the metabolism of lipoids of the cell membranes and regulation of hormones. I t is possible that the difficulties in carrying out successful therapy with antidepressant drugs may be caused by unknown hereditary factors concerning response to psyehotropie drugs. Up to now it is not confirmed whether genetic factors influence an effective therapy with tricyclie substances like imipramine or amitriptyline. However, the investigations of Angst (1964) showed that first degree relatives with endogenous