[Historical approach to reserpine discovery and its introduction in psychiatry]. / Aproximación histórica al descubrimiento de la reserpina y su introducción en la clínica psiquiátrica.

Reserpine, an alkaloid of the Rauwolfia serpentina plant isolated during the middle of the 20th Century, represented a highly important clinical advance in the treatment of schizophrenia whose pharmacological tools were limited to chlorpromazine that was introduced in the clinical area two years before. Both agents would come into the history as the drugs that made possible the beginning of the psychopharmacological era. In the present article, a revision is made of the complicated process leading to the isolation and synthesis of reserpine, by the Swiss pharmaceutical company Ciba (Schlittler and Müller) and how its pharmacological properties (Bein) were discovered and studied, in the animals laboratory, mainly, the "tranquillizers". The introduction of this antipsychotic in psychiatry, which was initiated in 1954 (half a century ago), and the results obtained in the first clinical studies, as well as the role played by researchers such as Kline, Delay, Noce, Hollister, Altschule, etc. are then described. In addition, and from a historical perspective, the discovery of the adverse effects of this drug, especially those of extrapyramidal nature (dyskinesia and akathisia), are studied, concluding with the reasons that produced its rapid clinical decline, among which the genesis of depressive pictures (phenomenon presently questioned) may be emphasized. Finally, the conclusion reached was that, although the clinical relevance of reserpine was not as evident and long lasting as chlorpromazine, its initial contribution to the treatment of schizophrenic patients was of maximum importance.

History and evolution of the monoamine hypothesis of depression.

The symptoms of depression can be improved by agents that act by various mechanisms to increase synaptic concentrations of monoamines. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic and/or serotonergic systems and that targeting this neuronal lesion with an antidepressant would tend to restore normal function in depressed patients. The hypothesis has enjoyed considerable support, since it attempts to provide a pathophysiologic explanation of the actions of antidepressants. However, in its original form it is clearly inadequate, as it does not provide a complete explanation for the actions of antidepressants, and the pathophysiology of depression itself remains unknown. The hypothesis has evolved over the years to include, for example, adaptive changes in receptors to explain why there should be only a gradual clinical response to antidepressant treatment when the increase in availability of monoamines is rapid. Still, the monoamine hypothesis does not address key issues such as why antidepressants are also effective in other disorders such as panic disorder, obsessive-compulsive disorder, and bulimia, or why all drugs that enhance serotonergic or noradrenergic transmission are not necessarily effective in depression. Despite these limitations, however, it is clear that the development of the monoamine hypothesis has been of great importance in understanding depression and in the development of safe and effective pharmacologic agents for its treatment.