Mental depression, biochemistry

The early pioneering work by Zeller et al. (115) on the potent MAO inhibitory effect of iproniazid—a structural modification of the tuberculostat Isoniazid—and his realization of the physiologic consequences that might arise from such a profound alteration in catecholamine metabolism, the actual confirmation by Brodie, Pletscher, and Shore (27) of the rise in brain monoamine levels following the administration of iproniazid and JB-516 (a-methylphen-ethylhydrazine), and the early euphoric effects noted by Selikoff, Robitzek, and Omstein (96) in tuberculosis patients on iproniazid therapy led Kline and his associates (67) to investigate the possible application of iproniazid in the treatment of mental depression. It was their conclusion that MAO inhibition and antidepressant effect had a causal relationship and that a new approach for the treatment of mental depression had been uncovered. The subject of the MAO inhibitors has been reviewed extensively up to 1960 by Pletscher, Gey, and Zeller (84) and by Biel, Horita, and Drukker (21) to 1963, in comprehensive reviews of the chemistry, biochemistry, pharmacology, clinical application, and structure-activity relationships of the MAO inhibitors. 

The biochemistry of mental depression is not fully understood, but a deficiency of norepinephrine and serotonin (possibly also dopamine see next section) almost certainly plays a role. Evidence is provided by the manner in which three classes of drugs, illustrated by the following three componnds, influence the action of these neurotransmitters. 

Serotonin has been found to influence sleeping, the regulation of body temperature, and sensory perception, but its exact role in mental illness is not yet clear. Unusually low levels of 5-hydroxyindoleacetic acid, a product of serotonin utilization, are characteristically found in the spinal fluid of victims of violent suicide. Drugs that mimic serotonin are sometimes used to treat depression, anxiety, and obsessive-compulsive disorder. Serotonin blockers are used to treat migraine headaches and relieve the nausea that accompanies cancer chemotherapy. A better understanding of the biochemistry of the brain may lead to better medications for treating various forms of mental illness. 

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