Heribert Konzett

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Heribert Konzett (born June 21, 1912 in Bludenz in Vorarlberg ; † November 4, 2004 in Innsbruck ) was an Austrian doctor and pharmacologist . He discovered the first substance that selectively activated β-adrenoceptors , namely isoprenaline .

Life

After studying in Innsbruck and Vienna, Konzett received his doctorate in Vienna in 1936. med. PhD. He then joined the Vienna Pharmacological Institute headed by Ernst Peter Pick , in the working group of Richard Rössler , who replaced Pick as head of the institute in 1938. Here he completed his habilitation in 1941. From 1946 to 1948 he worked in Cambridge with the pharmacologist Ernest Basil Verney , in London with the physiologist Henry Barcroft (1904–1998) and in Edinburgh with the physiologist Catherine Olding Hebb (1911–1978). From 1948 he headed the pharmacological laboratory of the Sandoz company in Basel, before taking over the chair for pharmacology and toxicology at the University of Innsbruck in 1958 as the successor to Adolf Jarisch . In 1980 he retired . His successor was Hans Winkler (* 1939).

plant

Konzett made the discovery of isoprenaline right from the start. The Viennese pharmacologists examined sympathomimetics synthesized by the company CH Boehringer Sohn , namely chemical derivatives of adrenaline . The main investigator was Klaus Unna , who left Austria in 1937 as a “ non-Aryan ” and was only able to publish his results in 1951 in Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . He provided the publication with the note: "This work was carried out in 1937 and is only now being published for external reasons." Unna's material included the substances synephrine (Sympatol), etilefrin , which were later used as medicinal substances - in some cases to this day. Phenylephrine and bamethane. In addition to toxicity, Unna only tested cardiovascular effects. In 1937 the idea came up of making adrenaline derivatives less effective for the circulation by using larger substituents on the amino group while retaining their inhibitory effect on the smooth muscles . A useful inhibitor for the smooth muscles of the airways , i.e. a bronchospasmolytic , could thus be found. Rössler was to lead this research direction and Konzett was to collaborate. First of all, the two of them developed a method based on animal experiments to measure airway resistance , later known as the “Konzett-Rössler method”. Then they tested adrenaline and five derivatives and found: “If you compare all the amines examined from the point of view of the broncholytic potency, a series results from the most effective isopropyladrenaline <= isoprenaline> via ethyladrenaline to the roughly equally effective bodies adrenaline, propyladrenaline, Butyladrenalin and eventually leads to the only weakly effective Isobutyladrenalin. "the rest of Pharmacology of the six substances, for example, the circulation effect, was clarified and 1940, the isoprenaline under the name" Aleudrin ", later" Aludrin ", for the treatment of bronchial asthma on the Brought to market. It was the first means of interrupting an asthma attack that lacked some of the undesirable side effects of adrenaline, and was very successful in Austria and Germany, after 1945 and the confiscation of the patent also with the former opponents of Germany. However, the adrenaline-like effect of the heart in overdosing has resulted in numerous deaths, around three thousand in the UK alone . Today, selective β 2 sympathomimetics, which are less dangerous , are used instead of isoprenaline . Isoprenaline has also become important for basic pharmacological research, especially the history of catecholamine research . With his help, Raymond Ahlquist divided the adrenoceptors into the two large groups α-adrenoceptors and β-adrenoceptors in 1948. Konzett wrote in 1981: “As a result, the reputation of this substance spread worldwide, and it became a tool for much research in pharmacology and therapy.” After the Science Citation Index , the publication by Konzett and Rössler in 1940 is the second most cited publication in the journal “Naunyn-Schmiedeberg's Archives of Pharmacology ”(cited 734 times from 1945 to 1990).

Konzett continued to work with isoprenaline and other sympathomimetics, for example during his time in England and Scotland together with Barcroft and Hebb. With Catherine Olding Hebb, he also studied the effects of morphine, pethidine and methadone on sympathetic ganglia . The joint publications also document the openness in the United Kingdom to young researchers from former enemy countries, as well as the interest there in drugs that were invented in Germany or Austria during the World War - pethidine and methadone are also included, both from the laboratories of the IG Farbenindustrie AG. With his third British teacher and partner Verney, Konzett gained insight into research on the antidiuretic hormone of the neurohypophysis . Verney realized during this time that it is released when the osmolarity of the blood increases . In the late 1950s, together with other scientists from Sandoz, Konzett analyzed the structure-activity relationships of the antidiuretic hormone and the second neurohypophyseal hormone, oxytocin .

Antidiuretic hormone and oxytocin are peptides . Peptide research flourished back then. Konzett's best-known result, next to the discovery of isoprenaline, is the determination - within the same group of Sandoz - of the structure of bradykinin , a peptide that plays a role as an inflammation mediator . The National Institute for Medical Research in Mill Hill, a district of London , tried to do this . The story of the apparently friendly competition, with errors, corrections and lively correspondence, has been told by the Basel as well as the London group. The Basel chemist Boissonnas wrote (from English): “The riddle would not have been solved so quickly without the friendliness and openness of Dr. Elliott <from Mill Hill> and the close collaboration between our team of chemists, including Dr. Guttmann, Dr. Jaquenoud and I belonged, and the pharmacology group of Professor Konzett and Dr. Striker."

Konzett was temporarily dean of the Innsbruck Medical Faculty. From 1967 to 1968 he was chairman of the German Pharmacological Society . In 1975 he published a history of Austrian pharmacology. Thanks to his proximity to the Sandoz chemist and LSD discoverer Albert Hofmann , he took part in a “psychopharmacological” experiment with Ernst Jünger , about which Hofmann reports:

“At the beginning of February 1951 there was a great adventure, an introduction to LSD with Ernst Jünger. ... That was before Aldous Huxley began to experiment with mescaline with the same question , which he reported on in his two books ' The Doors of Perception ' and 'Heaven and Hell'. In order to have medical help on hand if necessary, I asked my friend, the doctor and pharmacologist Heribert Konzett, to participate in our company. The entry took place at ten o'clock in the morning in the living room of our house in Bottmingen . Since the reaction of a highly sensitive person like Ernst Jünger could not be foreseen, a low dose was chosen as a precaution for this first attempt, only 0.05 milligrams. The experiment did not lead to great depths. The entry phase was characterized by intensifying the aesthetic experience. Red-purple roses took on an unprecedented luminosity and shone with a meaningful glow. … Konzett, whose facial features seemed to me transfigured as buddha, experienced a touch of timelessness, the liberation from past and future, the happiness of being here and now. The return from the changed state of consciousness was associated with a strong sensation of cold. ... All three of us had approached the gate to a mystical experience of being; but it did not open. The dose was chosen too low. "

The experience is reflected in Jünger's 1952 story Visit Godenholm .

student

The following scientists completed their habilitation at Konzett in Innsbruck:

  • Carl Job (* 1920, habilitation 1966)
  • Johann Klupp (* 1919, habilitation 1966, later head of research at Boehringer Ingelheim)
  • Hans Winkler (* 1939, Habilitation 1969; Konzett arranged for him to do research with Hermann Blaschko in Oxford, and he became Konzett's successor in Innsbruck)
  • Heide Hörtnagl (* 1943, habilitation 1977, later professor at the Pharmacological Institute of the Charité ).

recognition

Konzett was an honorary member of the German Pharmacological Society and the Austrian Pharmacological Society as well as a "real member" of the Austrian Academy of Sciences . The Graz pharmacologist Fred Lembeck published a sequel to his history of Austrian pharmacology from 1975, " In honor of Professor Heribert Konzett on his 90th birthday".

Since 2009, the Austrian Pharmacological Society has been awarding the Heribert-Konzett Prize, donated by the AstraZeneca Austria company, for achievements in the field of experimental or clinical pharmacology.

Individual evidence

  1. ↑ H. Wyklicky: On the history of the Pharmacological Institute of the University of Vienna (start-up problems , research personalities and selection of some key areas of expertise ). In: Wiener Klinische Wochenschrift 102, 1990, pp. 585-593.
  2. ^ Obituary on the website of the University of Innsbruck. Retrieved January 18, 2013.
  3. ^ H. Winkler: Obituary for Prof. Heribert Konzett. In: Biospektrum 11, 2005, p. 90. Retrieved January 18, 2013.
  4. ^ Ullrich Trendelenburg: Persecuted German-speaking pharmacologists 1933–1945. Frechen, Dr. Schrör Verlag, 2006, pp. 119-120. ISBN 3-9806004-7-5
  5. ↑ Klaus Unna: Pharmacological investigations on new Sympatolabkändlinge. In: Naunyn-Schmiedebergs Archive for Experimental Pathology and Pharmacology 213, 1951, pp. 207-234. doi: 10.1007 / BF02432757 .
  6. ↑ a b Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology. In: Naunyn-Schmiedeberg's Archives of Pharmacology 358, 1998, pp. 1-109 doi: 10.1007 / PL00005229
  7. ↑ Heribert Konzett and Richard Rössler: Experimental arrangement for examinations of the bronchial muscles. In: Naunyn-Schmiedebergs Archive for Experimental Pathology and Pharmacology 195, 1940, pp. 71-74. doi: 10.1007 / BF01861842
  8. ↑ Heribert Konzett: New broncholytic highly effective bodies of the adrenaline series. In: Naunyn-Schmiedebergs Archive for Experimental Pathology and Pharmacology 197, 1941, pp. 27-40. doi: 10.1007 / BF01936304
  9. ↑ Heribert Konzett: On the pharmacology of new adrenaline-related bodies. In: Naunyn-Schmiedebergs Archive for Experimental Pathology and Pharmacology 197, 1941, pp. 41-56. doi: 10.1007 / BF01936305
  10. ↑ Walter Sneader: Drug Discovery: The Evolution of Modern Medicines. John Wiley & Sons, Chichester, 1985, p. 103. ISBN 0-471-90471-6 .
  11. ^ H. Konzett: On the discovery of isoprenaline. In: Trends in Pharmacological Sciences 2, 1981, pp. 47-49. doi: 10.1016 / 0165-6147 (81) 90259-5
  12. ^ H. Barcroft and H. Konzett: On the actions of noradrenaline, adrenaline and isopropyl noradrenaline on the arterial blood pressure, heart rate and muscle blood flow in man. In: The Journal of Physiology 110, 1949, pp. 194-204. PMC 1392773 (free full text)
  13. ^ CO Hebb and H. Konzett: Vaso- and bronchodilator effects of N-isopropyl-norepinephrine in isolated perfused dog lungs . In: Journal of Pharmacology and Experimental Therapeutics . 96, 1949, pp. 228-237.
  14. ^ CO Hebb and H. Konzett: Difference between morphine and synthetic analgesics in their actions on ganglionic transmission. In: Nature 163, 1949, pp. 720-721. doi: 10.1038 / 163720a0
  15. ^ H. Konzett and E. B: Verney: Observations on the urine, blood and arterial pressure of dogs before and after the production of renal ischaemia. In: Journal of Physiology 107, 1948, pp. 336-345. PMC 1392182 (free full text)
  16. ^ RA Boissonnas, St. Guttmann, B. Berde and H. Konzett: Relationships between the chemical structures and the biological properties of the posterior pituitary hormones and their synthetic analogues. In: Experientia 17, 1961, pp. 377-390. doi: 10.1007 / BF02157958
  17. ^ RA Boissonnas, St. Guttmann, P.-A. Jaquenoud, H. Konzett and E. Stürmer: Synthesis and biological activity of peptides related to bradykinin. In: Experientia 16, 1960, p. 326. doi: 10.1007 / BF02157779
  18. ^ H. Konzett and E. Stürmer: Biological activity of synthetic polypeptides with bradykinin-like properties. In: British Journal of Pharmacology 15, 1960, pp. 544-551. PMC 1482266 (free full text)
  19. ↑ H. Konzett and E. Stürmer: Synthetic bradykinin: its biological identity with natural pure trypsin bradykinin. In: Nature 188, 1960, p. 998. doi: 10.1038 / 188998a0
  20. ↑ A. Cerletti, E. Stürmer and H. Konzett: Bradykinin. Structure elucidation, synthesis, physiological-pharmacological principles. In: Deutsche Medizinische Wochenschrift 86, 1961, pp. 678-683. doi: 10.1055 / s-0028-1112842
  21. ↑ a b R.A. Boissonnas: The synthesis of bradykinin. In: Biochemical Journal 10, 1962, pp. 35-38. doi: 10.1016 / 0006-2952 (62) 90214-9
  22. ^ GP Lewis: The purification and structural elucidation of bradykinin - a reminiscence of 1960. In: Immunopharmacology 43, 1999, pp. 97-101. doi: 10.1016 / S0162-3109 (99) 00127-7
  23. ^ H. Konzett: 70 years of Austrian pharmacology. In: Subsidia medica - Journal for Drug Therapy 27, 1975, pp. 1-6.
  24. ↑ Albert Hofmann: LSD - My problem child. Ernst Klett, Stuttgart 1979, pp. 174-175. ISBN 3-12-923601-5 .
  25. ↑ Hans Winkler: Institute for Pharmacology at the Medical University (formerly the Medical Faculty of the Leopold-Franzens University) Innsbruck. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 353–359. ISBN 3-85093-180-3 .
  26. ^ Fred Lembeck: Pharmacology in Austria in the 20th century: In honor of Professor Heribert Konzett on his 90th birthday. In: Wiener Klinische Wochenschrift. 115, 2003, pp. 200-207. doi: 10.1007 / BF03040311
  27. ↑ Articles of Association on the company's website. (PDF; 37 kB) Retrieved September 30, 2013.
personal data
SURNAME Konzett, Heribert
BRIEF DESCRIPTION Austrian doctor and pharmacologist
DATE OF BIRTH June 21, 1912
PLACE OF BIRTH Bludenz
DATE OF DEATH November 4, 2004
Place of death innsbruck