Mechanisms Of Action

MAOs are intracellular enzymes found throughout the body, with most bound tightly to the outer mitochondrial membrane (11,12). The MAOs oxidatively deam-inate monoamines in the presence of oxygen (13). MAO-A is the primary form in the intestine, pancreas, and spleen, and the sole form in human placenta (14-16). MAO-B predominates in skin and skeletal muscle, and is the sole form in platelets. Although the human liver contains both forms, MAO is absent in plasma and red blood cells (17). Human brain MAO is 70% to 80% type B (18), whereas MAO-A predominates in rodent brain (19).

MAO-A in the brain is found in the locus ceruleus, nucleus subceruleus, periventricular regions of the hypothalamus, and striatal dopaminergic neurons (20,21). MAO-A content of primate substantia nigra is low, relative to the number of tyrosine hydroxylase positive cells (21). Astrocytes are the main repository of brain MAO-B (21). With increasing age, human brain MAO-B but not MAO-A activity increases (22). The rate of increased activity varies between brain regions; higher in the basal ganglia and substantia nigra than the cerebral cortex or medulla (22). Glial MAO-B activity is reported to increase in neurodegenerative disorders (22).

Both MAO-A and MAO-B catabolize dopamine, epinephrine, norepinephrine, tyramine, tryptamine, 3-methoxytyramine, and kynuramine (23). MAO-A primarily catabolizes serotonin and octopamine and MAO-B metabolizes benzy-lamine, phenylethylamine, milacemide, and N-methylhistamine. MAO-B also converts the protoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to 1-methyl-4-phenyl-pyridium ion (MPP+) (23). MAO-A and MAO-B are structurally similar, and the flavin sites on each are identical (24). True selectivity of most MAO inhibitors is present only at low concentrations (25).

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