An update on the identity crisis of monoamine oxidase: new and old evidence for the independence of MAO A and B.

The monoamine oxiclases (MAO; EC 1.4.1.4), named by Zeller in 1938, are widely distributed in the animal kingdom (Blaschko, 1974; Hall and Uruena, 1983) and oxidize many biogenic and xenobiotic amines in the central nervous system and peripheral tissues. Thirty five years ago, MAO drew the attention of psychiatrists and pharmacologists when MAO inhibitors were found to be therapeutically effective in the treatment of clinical depression (reviewed in Fowler and Ross, 1984). In recent years, MAOs have been the subject of numerous articles and symposia (see recent collections edited by Singer et al., 1979; Youdim and Paykel, 1980; Kamijo et al., 1982; Tipton et al., 1984). Although use of these drugs in the treatment of depression fell into disfavor in the 1960s because of renal side effects and cardiovascular complications (the 'cheese effect'; Cooper and Keddie, 1964; Glazener et al., 1964; Natoff, 1964), MAO inhibitors which induce no or less severe cardiovascular side effects have since been developed (Knoll, 1976; EIsworth et al., 1978; Dollery et al., 1984). The antidepressant activity of MAO inhibitors and tricyclic antidepressants has generally been ascribed to their ability to increase amine concentrations available to interact with postsynaptic receptors. Because of the antidepressant activity of MAO inhibitors, a large number of clinical studies have compared MAO activities in normal individuals and patients with a variety of brain and metabolic disorders (reviewed by Sandier and Youdim, 1972; Sullivan et al., 1980; Wyatt et al., 1980; Sandler et al., 1981; Murphy, 1984). As summarized by Bridge et al. (1985), lowered platelet MAO activities have been reported in schizophrenia, bipolar affective disorders, alcoholism, cycloid psychoses, attention deficit disorder in children, epilepsy, insulin-dependent diabetes, Lesch-Nyhan syndrome, migraine headache, iron deficiency anemia, riboflavin deficiency, Down's syndrome, toxemia of pregnancy and thyrotoxicosis (see also reviews by Wyatt et al., 1980; Fowler et al., 1982; Murphy, 1984). In contrast, elevated levels of MAO B activity have been observed in schizoaffective schizophrenia, unipolar depression (see discussion by Murphy, 1984), senile dementia (Adolfsson et al., 1980; Smith et al., 1982), and Huntington's chorea (Adolfsson et al., 1980; Smith et al., 1982). Although platelet MAO levels vary over more than a 10-fold range in the human population, no disorder has yet been shown to result from a total deficiency of MAO. It has been reported that the MAO B inhibitor deprenyl when used in combination with L-DOPA provides symptomatic relief in parkinsonism, and may reduce the rate of progression of the disease (Youdim et al., 1979, 1985). Combining deprenyl with L-DOPA therapy was attempted because deprenyl was expected to inhibit dopamine degradation, and thereby lead to an increase in the efficacy of dopamine produced from L-DOPA. An additional rationale for the use of deprenyl in the treatment of Parkinson's