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Friday, 24.03.2017

In Memoriam

Fridolin Sulser

Grabs, Switzerland, December 2, 1926 – Nashville, Tennessee, United States, March 1, 2016


Carlos Morra

Fridolin Sulser was interviewed on May 9, 1997 in Nashvile, Tennessee, USA,by Leo E. Hollister for the Oral History Series of the American College of Neuropsychopharmacolgy, and the edited transcript of this interview was published in Volume 3 (Neuropharmacology) of the series (Ban 2011; Sulser 2011). A transcript of the same interview with further editing was posted in INHN’s Educational E-Books that included all interviews conducted by Hollister  in the Oral History project (Martin and Ban 2014).

The entry on Sulser, in the Dramatis Personae of the volume editor (Fridolin Sulser) reads: “Fridolin Sulser received his MD degree in 1955 from the University of Basel, Switzerland. From 1956 to 1958, he was an Assistant Professor of Pharmacology at the University of Bern, Switzerland. In October 1958, he moved to the Laboratory of Chemical Pharmacology at the National Heart Institute, NIH, in Bethesda as an International Postdoctoral Research Fellow and became a Visiting Scientist from 1961 to 1963. After a short tenure as Head of the Department of Pharmacology at the Welcome Research Laboratories, in Tuckahoe, NY,  he moved back to academia in 1965 as Professor of Pharmacology and Psychiatry at  Vanderbilt University School of Medicine, in Nashville and then Director of the Tennessee Neuropsychiatric Institute. In 1986, he spent his Sabbatical year as a Visiting Scientist at the Roche Institute of Molecular Biology in Nutley, NJ. In 2000, he became an Emeritus Professor of Pharmacology and Psychiatry. In Switzerland Sulser’s research was focused on experimental hypertension, particularly the role of the renin–angiotensin system and its modification by adrenal corticoids and the action of digitalis on ion transport. As a postdoctoral Fellow with  Brodie, he switched his research interests to neuropsychopharmacology. He has made many contributions to the field, among them the discovery of the first clinically efficacious secondary amine of noradrenergic tricyclics, desmethylimipramine (DMI,) formed in vivo by oxidative N-demethylation of imipramine. DMI turned out to be the first selective inhibitor of high affinity uptake of NE. During the early 1970s, Sulser and Jerzy Vetulani discovered that antidepressant treatments, if administered chronically, reduced selectively the responsiveness of beta adrenoceptor coupled adenylate cyclase in brain. His later studies on the phosphorylation of the transcription factor, CREB, by protein kinase A supported the notion of a net deamplification of the NE signal. Fridolin Sulser and his colleagues provided the first provocative evidence that tricyclic antidepressants can regulate steady state glucocorticoid mRNA levels in vivo by a mechanism that is independent of effects on synaptic NE. He then demonstrated an impairment of the activation of protein kinase A via the beta adrenoceptor /cyclic AMP cascade in subcultured fibroblasts of patients with major depression. A number of his “pre-retirement” studies led to the heuristic view that dysregulation of molecular communication between the three integrative systems; nervous, endocrine and immune, is the cause of or creates predisposition to, psychiatric illnesses such as depression. Fridolin Sulser belongs to numerous prestigious societies, including the ACNP, CINP, ASPET, IBRO, Society of Neuroscience, the Society of Biological Psychiatry and was president of ACNP in 1979. He is recipient of the Anna Monika Award, the Gold Medal Award of the Society of Biological Psychiatry, a Ten Year Merit Award of the NIMH and the CINP Pioneer in Psychopharmacology Award. He is also an Honorary Fellow of the American College of Psychiatrists (Sulser 2011”).

            In the same volume, Thomas A. Ban, the series editor of An Oral History of Neuropsychopharmacology summed up Sulser’s sontributins as follows: “Fridolin Sulser, another Brodie disciple was first in the early 1960’s to recognize that reserpine reversal was dependent on the availability of NE (Sulser, Bickel and Brodie 1964). He found that DMI no longer reversed the effects of reserpine after depleting brain NE by α-methyltyrosine (Sulser 1998). In the mid-1970s, in collaboration with Jerzy Vetulani, Sulser discovered that chronic treatment with tricyclic and MAOI antidepressants (as well as with ECT) decreased the number of β-adrenoreceptors, and reduced the responsiveness of the β-adrenoreceptor-coupled adenylate cyclase system to NE in limbic and cortical structures in the rat brain (Vetulani and Sulser 1975). Pursuing this line of research further, with a shift in emphasis from pre-synaptic to post-synaptic mechanisms, he found in collaboration with Sanders-Bush, that both NE, through the activation of the cyclic AMP - proteinkinase A pathway, and 5HT, through the activation of the diacylglycerol (DAG) -  protein kinase C pathway, caused phosphorylation of nuclear CREB (cyclic adenosine monophosphate regulated element binding protein) (Sanders-Bush, Conn and Sulser 1985). Furthermore, in collaboration with Manier and Shelton, he also revealed that chronic treatment with noradrenergic antidepressants produced a highly significant reduction (down–regulation) of CREB - P, the biologically active form of the transcription factor(Manier, Shelton and Sulser 2002)” (Ban 2011).

            An “Autobiographical Account of Fridolin Sulcer was published with the title My Becoming a Psychopharmacologist: New Drugs and New Concepts, in Volume 4 of CINP’s The History of Psychopharmacology and the CINP (Ban, Healy and Shorter 2004).


Ban TA. Preface. In Ban TA editor. An Oral History of Neuropsychoparmacology. The First Fifty Years. Peer Interviews. Volume 3 (Sulser F, editor. Neuroparmacology). Brentwood: ACNP; 2011.p. xviii.

Manier DH, Shelton R, Sulser F. Noradrenergiantidepressants: does chronic treatment increase or decrease CREB-P? J Neurol Transm 2002; 109: 91-9.

Martin M, Ban TA, editors. Recollections of the History of Neuropsychopharmacology Through the Interviews of Leo E. Hollister. INHN. E-Books. February 6, 2014.

Sanders-Bush E, Conn J, Sulser F. The serotonin/norepinephrine - linked β-adrenreceptor system and the mode of action of antidepressants. Psychopharmacol Bull 1985; 21: 373-8.

Sulser F. My becoming a psychopharmacologist. New drugs and new concepts. An autobiographica accout. In Ban TA, Healy D, Sulser F, editors. Reflections on Twenteth-Century Psychopharmacology. Volume 4 of the series The History of Psychopharmacolog and  the CINP. As Told in Autobiography. Budapest: Animula; 2004, pp. 299-307

Sulser F. My early years with tricyclics. In: Ban TA, Healy D, Shorter E, editors. The Rise of Psychopharmacology and the Story of CINP. Budapest: Animula; 1998. p. 81-3.

Sulser F. editor. Neuropharmacology. (Ban TA, series editor. An Oral History of Neuropsychopharmacology.).Brentwood: ACNP; 2011. 

Sulser F, Bickel MH, Brodie BB. The action of desmethylimipramine in counteracting sedation  and cholinergic effects  of reserpine-like drugs. J Pharmacol Exp Ther 1964; 144: 321-3.

Vetulani J, Sulser F. Action of various antidepressant treatments reduces the reactivity of the noradrenergic cyclic AMP–generating system in limbic forebrain. Nature 1975; 257: 495-6.


Carlos Morra

August 18, 2016