Biogenic amines and depression (Introduction to symposium)

The involvement of biogenic amines--primarily noradrenaline (NA) and serotonin (5-HT)--in depressive disorders was suggested by the finding more than twenty years ago that imipramine possessed antidepressant properties and concomitantly altered the availability of NA in the brain. Since then, numerous antidepressants closely related chemically and pharmacologically to imipramine have been introduced. It has generally been assumed that these "tricyclics" alleviate depression by influencing the neurotransmitters (NA, 5-HT) at crucial receptor sites in the brain. Thus, the "biogenic amine hypothesis of depression" postulates that depression is due to a reduced functional activity of one or more brain amines. The tricyclics appear to be antidepressants due to their inhibition of the neuronal reuptake of NA in the brain. A decade ago, Carlsson, Coppen, Lapin, van Praag and other suggested that compounds selectively affecting the 5-HT uptake mechanism might be more effective antidepressants. This symposium will describe the clinical and preclinical results with zimelidine--the first 5-HT-selective uptake inhibitor.