By Fridolin Sulser
Alfred Pletscher was born in 1917 in Altstaetten/ SG, Switzerland. He received both his M.D. degree in 1942 and his Ph.D. in chemistry in 1948 from the University of Zurich, Switzerland. After a year as Visiting Scientist with Bernard B. Brodie at the National Heart Institute of the National Institutes of Health (NIH), he returned in 1955 to Switzerland to assume the position of Director of Corporate Research at Hoffmann - La Roche, Basel. “My time in Brodie’s laboratory was one of the highlights of my scientific career” he said. In an interview with Tom Ban, Pletscher reflected on his position in industry: “My primary motivation in industry was not profit, but helping people.” This statement is an expression of Pletscher’s humanistic philosophy. In 1978, he left industry and became Chairman of the Department of Research at the University of Basel.
Alfred Pletscher’s scientific contributions had an enormous impact on the development of Biochemical Neuropsychopharmacology worldwide. In 1955, together with Parkhurst Shore and Bernard B. Brodie, Alfred Petscher demonstrated using spectrofluorimetric methodology that reserpine’s tranquilizing action is associated with a dose-dependent depletion of brain serotonin (5HT) (1). This finding opened up world-wide research on the neurobiology of monoamines (2). Pletscher was first to demonstrate that pretreatment with iproniazid , a monoamine oxidase (MAO) inhibitor, not only attenuated the reserpine-induced decrease of brain 5HT but was associated with behavioral stimulation by reserpine instead of tranquilization. Since the reserpine-like syndrome was viewed as a “model depression,” the discovery provided the scientific rationale for the introduction of MAO inhibitors for the treatment of depression (3). It also stimulated research for mechanisms of action of tricyclic antidepressants which, like iproniazid, also antagonized the “reserpine-like syndrome” but without blocking MAO, culminating in the discovery by Axelrod and Herting of the reuptake mechanism for the non-enzymatic termination of the action of biogenic amines.
When Pletscher returned to Switzerland, he developed the synthetic benzoquinolizines -tetrabenazine and Ro- 41284 - which displayed a short-lived reserpine-like syndrome associated with a short-lived depletion of brain 5HT, and were widely used as tools to discover “antidepressant “ activity in laboratory animals (4).
Pletscher was also instrumental in introducing the benzodiazepines, discovered by Leo Sternbach at Roche in Nutley, USA - chlordiazepoxide (Librium) first, followed by diazepam (Valium) – for the treatment of anxiety disorders.
Another pivotal contribution to the monoamine field was the development of decarboxylase inhibitors and their combination with levodopa for the treatment of Parkinson disease (5). Pletscher’s rationale for the combination was based on the discovery that these decarboxylase inhibitors enhanced the levodopa-induced rise in brain dopamine while they decreased` the concentration of peripheral dopamine. This combination of levodopa with a peripheral decarboxylase inhibitor is still a standard treatment of Parkinson’s disease.
In meticulously designed studies, Alfred Pletscher utilized blood platelets as models for brain neurons to study uptake, storage, release and metabolism of biogenic amines and receptors for monoamines and peptides.
Collectively, Alfred Pletscher’s scientific contributions have provided the conceptual framework for much of what we are doing today, e.g., studies on amine transporters, amine receptor mediated second messenger formation, activation of protein kinases. His pioneering research endeavors` and his scientific astuteness did not go unnoticed by the political authorities in Switzerland. Thus, in 1981, he was elected President of the research council of the Swiss National Science Foundation and in 1988, President of the Swiss Academy of Medical Sciences. Alfred Pletscher catalyzed the creation of the Biocenter of the University of Basel, the Roche Institute of Molecular Biology in Nutley, USA and the prestigious Basel Institute of Immunology.
Alfred Pletscher received many honors, among them four Honorary Doctor degrees from the Universities of` Paris (France), Geneve, Lausanne, and Fribourg (Switzerland); the prestigious Marcel Benoist Prize, the Science Prize of the city of Basel and the CINP Pioneer in Psychopharmacology Award.
Alfred Pletscher, a true Pioneer of Psychopharmacology, passed away, age 90, on Decmber 12, 2006.
1.Pletscher A, Shore PA, Brodie BB. Serotonin release as a possible mechanism of action of reserpine. Science; 1955; 122: 374 - 375.
2. Pletscher A. The dawn of the neurotransmitter era in neuropsychopharmacology. In: Ban TA, Ucha Udabe R, eds. The Neurotransmitter Era in Neuropsychopharmacology Buenos Aires: Polemos; 2005, pp. 27-37.
3. Pletscher A, Gey KF, Zeller P. Monoamineoxydase – Hemmer. Biochemie, Chemie, Pharmakologie, Klinik. In: Jucker E, editor. Progress in Drug Research, volume 2. Basel/Stuttgart: Birkhäuser Verlag; 1960, pp. 419-590.
4. Pletscher A. Release of 5-hydroxytryptamine by benzoquinolizine derivatives with sedating action. Science 1957; 126: 507. .
5. Pletscher A, Gey KF, Burkard WP. Inhibitors of monoamineoxidase and decarboxylase of aromatic acids. In: Eichler O, Farah A, editors. Handbook of Experimental Pharmacology, volume 19. Berlin: Springer; 1965, pp. 593 – 735.
November 28, 2013