Klaus Unna

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Klaus Unna , full name Klaus Robert Walter Unna (born July 30, 1908 in Hamburg, † June 26, 1987 in Santa Fe , New Mexico ) was a German-American doctor and pharmacologist . He primarily researched the pharmacology of the nervous system and contributed to the development of therapeutically used sympathomimetics , opioid antagonists and tranquilizers .

Life

He was the son of the dermatologist Karl Unna (1880–1964) and his wife, the dermatologist Marie Unna geb. Boehm. In 1930 he was in Freiburg to the Dr. med. PhD. After his time as a medical assistant , he worked in 1932 and 1933 with the physiologist Klotilde Gollwitzer-Meier (1894–1954) at the Balneological Institute in Bad Oeynhausen , today's Gollwitzer-Meier Clinic . In 1933 he left Germany as a non-Aryan because of the Nazi seizure of power and went to Austria, where he joined the Pharmacological Institute of the University of Vienna , headed by Ernst Peter Pick . In 1937 political developments caused him to leave Austria as well. With the help of the former assistant at the Vienna Institute, Hans Molitor , who had emigrated in 1932 , he found a new position at the Merck Institute for Therapeutic Research in Rahway , New Jersey , founded by the latter . In 1944 he moved to the Pharmacological Department of the University of Pennsylvania in Philadelphia , Pennsylvania and in 1945 on to the Pharmacological Department of the University of Illinois in Chicago , Illinois , which he headed from 1955 to 1976 as full professor . He was married to Maya geb. Großmann, daughter of the Viennese publicist Stefan Großmann , with whom he had a son.

research

In Vienna, Unna worked on the antidiuretic hormone or vasopressin , one of Pick's areas of interest, and with Richard Rössler, eleven years his senior, on the function of the pericardium . He was only able to publish his most interesting results in 1951. "In a very sophisticated study" he examined eight sympathomimetics synthesized by the company CH Boehringer Sohn in Ingelheim am Rhein , relatives of adrenaline . Two were later marketed as drugs , the predominantly vasoconstricting etilefrine and the predominantly vasodilating bamethane . Unna wrote under the 1951 article in Naunyn-Schmiedeberg's Archive for Experimental Pathology and Pharmacology : "This work was carried out in 1937 and is only now being published for external reasons."

“The change from the friendly and harmonious atmosphere in the Viennese institute, which is characterized by teaching and research, to the working style in the laboratory of a pharmaceutical industry geared towards efficiency and practical applicability was not easy for Unna, but he approached the new task with his own energy . "his first subjects were part alkaloids of coral trees , shrubs or trees of the Pea family genus of Erythrina . It was known that extracts from the plants, as peripheral muscle relaxants, paralyzed animals. Together with chemists from the Merck Institute for Therapeutic Research, Unna isolated individual alkaloids such as β-erythroidin and characterized their effects. Unlike the curare alkaloids, which are quaternary ammonium compounds , they were tertiary amines and were therefore absorbed from the gastrointestinal tract and were also effective when administered orally. Today they are among the classic competitive nicotine receptor antagonists . At that time, muscle relaxants were still young as auxiliary materials in anesthesiology , and Unna continued to work with them in his later university days, for example describing their testing on humans in several articles.

In a not entirely fair exchange of information with the group of pharmacologist Chauncey D. Leake (1896–1978) in San Francisco , the Merck Institute developed the first clinically used opioid antagonist N-allyl-normorphine or nalorphine . Leake's group had started in 1940, but difficulties with the synthesis led him to contact Merck . The Merck chemists were quick and published their findings in 1942 without mentioning the California scientists. Unna's pharmacological analysis in 1943 already shows, as has been confirmed since then, that nalorphine is not a pure antagonist, but a partial agonist . “Personally, Unna was not particularly interested in nalorphine. but as a specialist, the ambition to do the analysis well. His pride as an independent scientist also probably made him hesitate to pursue an idea that was not his own. In the introduction of the article he correctly mentions Leake's suggestion. ”He also mentions that the pharmacologist Julius Pohl in Prague had already described an opioid antagonist in 1915 , N-allyl-norcodeine, which perhaps had no consequences because of the First World War .

In the mid-1940s, the pharmacologist Frank Milan Berger (1913–2008), who was then working in London, found myanesin or mephenesin , which sedated test animals , acted as a tranquilizer ("caused tranquillization") and relaxed the muscles via points of attack in the central nervous system was a central muscle relaxant . Unna recognized a principle of its effect: it inhibited the transfer of information to interneurons of the central nervous system and became "the first interneuron blocking drug". Berger looked for therapeutically better derivatives and found in 1950, meanwhile at Wallace Laboratories in New Jersey , the Meprobamat or Miltown , "a new interneuron blocking substance - a new interneuronal blocking drug". Meprobamat became the first clinically successful tranquilizer and the real counterpart to the fictional soma far beyond medicine . from Aldous Huxley's 1932 novel “ Brave New World ”. Around 1960 it was largely replaced by the benzodiazepines .

Basic research includes Unna's work on the muscarinic receptors , the second large group of receptors for acetylcholine alongside the nicotine receptors. He further characterized the mode of action of the recently discovered agonist McN-A-343 . The substance later contributed to Ullrich Trendelenburg's differentiation of receptors of sympathetic ganglion cells and even later to the differentiation of five muscarinic receptors.

recognition

Unna was Honorary Executive Secretary of the International Brain Research Organization (IBRO), which he helped establish in 1961. In 1970 the German Pharmacological Society made him an honorary member. In 1983 he became a corresponding member of the Austrian Academy of Sciences .

literature

Web links

Individual evidence

  1. ↑ Marie Unna ( Memento of the original from September 27, 2013 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. in women doctors in the empire. @1@ 2Template: Webachiv / IABot / web.fu-berlin.de
  2. ^ Kurt Kramer: Klothilde Gollwitzer-Meier 1894–1954. In: Results of Physiology, Biological Chemistry and Experimental Pharmacology . 49, 1957, pp. 48-58.
  3. ↑ Klaus Unna. In: Chicago Tribune. July 4, 1987, Retrieved February 12, 2013.
  4. ^ 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
  5. ↑ Klaus Unna: Pharmacological investigations on new Sympatolabkändlinge. In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology. 213, 1951, pp. 207-234. doi: 10.1007 / BF02432757 .
  6. ↑ Konzett 1988.
  7. ^ Karl Folkers, Klaus Unna: Erythrina alkaloids. II. A revew, and new data on the alkaloids of species of the genus erythrina. In: Journal of the American Pharmaceutical Association 27, 1938, pp. 693-699. doi: 10.1002 / jps.3080270815
  8. ↑ Klaus Unna, Michael Kniazuk, JG Greslin: Pharmacologic action of erythrina alkaloids. I. β-erythroidine and substances derived from it. In: Journal of Pharmacology and Experimental Therapeutics 80, 1944, pp. 39-52.
  9. ^ WC Bowman: Peripherally acting muscle relaxants. In: MJ Parnham, J. Bruinvels (Eds.): Discoveries in Pharmacology. Volume 1. Elsevier, Amsterdam 1983, ISBN 0-444-80493-5 , pp. 105-160.
  10. ↑ Linda P. Dwoskin, Peter A. Crooks: Competitive neuronal nicotinic receptor antagonists: a new direction for drug discovery. In: Journal of Pharmacology and Experimental Therapeutics. 298, 2001, pp. 395-402.
  11. ↑ KR Unna, EW Pelikan, DW Macfarlane, RJ Cazort, MS Sadove, JT Nelson, AP Drucker: Evaluation of curarizing drugs in man. I. Potency, duration of action, and effets on vital capacity of D-tubocurarine, dimethyl-D-tubocurarine, and decamethylene-bis (trimethylammonium bromide). In: Journal of Pharmacology and Experimental Therapeutics. 98, 1950, pp. 318-329.
  12. ^ A b Klaus Unna: Antagonistic effect of N -allyl-normorphine upon morphine. In: Journal of Pharmacology and Experimental Therapeutics. 79, 1943, pp. 27-31.
  13. ^ Kennon M. Garrett, E. Leong Way: The history of narcotic antagonists. In: MJ Parnham, J. Bruinvels (Eds.): Discoveries in Pharmacology. Volume 1. Elsevier, Amsterdam 1983, ISBN 0-444-80493-5 , pp. 379-393.
  14. ↑ FM Berger, W. Bradley: The pharmacological properties of α: β dihydroxy-γ- (2-methylphenoxy) propane (myanesin). In: British Journal of Pharmacology. 1, 1946, pp. 265-272. PMC 1509753 (free full text)
  15. ^ Elwood Henneman, Arnold Kaplan, Klaus Unna: A neuropharmacological study on the effect of myanesin (Tolserol) on motor systems. In: Journal of Pharmacology and Experimental Therapeutics. 97, 1949, pp 331-341.
  16. ^ WLM Perry: Central and synaptic transmission (pharmacological spects). In: Annual Review of Physiology . 18, 1956, pp. 279-308. doi: 10.1146 / annurev.ph.18.030156.001431 .
  17. ↑ FM Berger: The pharmacological properties of 2-methyl-2- n -propyl-1,3-proprandiol dicarbamate (Miltown), a new interneuronal blocking agent. In: Journal of Pharmacology and Experimental Therapeutics. 112, 1954, pp. 413-423.
  18. ↑ Satoshi Murayama, Klaus R. Unna: Stimulant action of 4- ( m -chlorophenylcarbamoyloxy) -2-butynyltrimethylammonium chloride (McN-A-343) on sympathetic ganglia. In: Journal of Pharmacology and Experimental Therapeutics. 140, 1963, pp. 183-192.
  19. ↑ Frederick J. Mitchelson: The pharmacology of McN-A-343. In: Pharmacology & Therapeutics . 135, 2012, pp. 216-245. doi: 10.1016 / j.pharmthera.2012.05.008
personal data
SURNAME Unna, Klaus
ALTERNATIVE NAMES Unna, Klaus Robert Walter
BRIEF DESCRIPTION German-American doctor and pharmacologist
DATE OF BIRTH July 30, 1908
PLACE OF BIRTH Hamburg
DATE OF DEATH June 26, 1987
Place of death Santa Fe , New Mexico