Ulrich Schwabe

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Ulrich Schwabe (born July 19, 1935 in Göttingen ) is a German doctor and pharmacologist . In basic experimental research, he made a particular contribution to the knowledge of the body's own messenger substance and tissue hormone adenosine . In application-related research, he tries to ensure the safety and economic efficiency of medicinal therapy .

Ulrich Schwabe

Life

Ulrich Schwabe is one of four children of the physician couple Rudolf Schwabe and Anneliese Schwabe born. Goebel. In 1954 he put on Hölty -Gymnasium in Wunstorf the matriculation examination from. He then studied medicine in Göttingen and Vienna . In 1959 he was awarded a PhD with the dissertation “Release of 5-hydroxytryptamine ( serotonin ) from various tissues of guinea pigs in acute and protracted anaphylactic shock ” , prepared by Ludwig Lendle (1899–1969) at the Pharmacological Institute of the Georg-August University in Göttingen. med. PhD. 1961 as a doctor approved , he worked on Institute at Göttingen Pharmacology, where he in 1966 with the work "inhibition of fatty acid mobilization by 3.5-Dimethyl-and its effect on the metabolism of fatty acids" for Pharmacology and Toxicology habilitated . In 1968 he moved to the Pharmacological Institute of the Hannover Medical School , headed by Erik Westermann (1923–1978) . 1975 to 1976 led him to a research stay in the research group of John William Daly (1933-2008) at the National Institutes of Health in Bethesda in the US state of Maryland .

In 1979 he succeeded Robert Domenjoz (1908-2000) at the chair for pharmacology and toxicology at the Rheinische Friedrich-Wilhelms-Universität Bonn . Martin Lohse , who joined the group in April 1983 (and Schwabe's first habilitation student), later remembered “the huge ordinary room in the Bonn institute, an Art Nouveau villa with a wonderful park, but otherwise only well equipped in our laboratories, while in other parts Villa and park very obscure things happened: Arthritis research on old chickens, whose eggs were Saturdays carried to the market, and the search for inflammatory factors in crushed rat paw "after four years of Bonn, in 1983, followed Schwabe a reputation as a successor. Franz Gross on the Pharmacology chair at the Ruprecht-Karls-Universität Heidelberg . His successor in Bonn was Manfred Göthert . In 1992 the Heidelberg Institute was divided into three departments, a “Department of General Pharmacology”, which Schwabe took over, a “Department of Pharmaceutical Pharmacology” and a “Department of Molecular Pharmacology”. When Schwabe retired in 2003, the division was reversed and Stefan Offermanns became his successor as head of the entire institute . Schwabe continues to live in Heidelberg. With his wife Gudula geb. He has three children from Bülow.

Experimental pharmacology

Release of serotonin

Schwabe's dissertation is one of the numerous investigations into the release of chemical messenger substances from cells into the extracellular space during allergic reactions. Serotonin appears to be particularly released from platelets .

Enzyme induction by DDT

The young assistant in Göttingen turned to another topic, the consequences of the storage of the insecticide dichlorodiphenyltrichloroethane (DDT) in tissue, especially adipose tissue . A suggestion came from the Pharmacological Institute of the Free University of Berlin . In 1962, employees of the institute's director, Hans Herken, reported that the insecticide hexachlorocyclohexane (HCH) shortened the sleep duration of test animals after administration of pentobarbital ; The cause was a faster breakdown of the barbiturate by means of the enzyme induction discovered by Herbert Remmer at the Berlin Institute . "Similar properties of DDT would be of interest, as it is eliminated approximately 3–4 times more slowly than HCH and, due to the greater accumulation, could cause more pronounced changes." The similarity was confirmed. This is how the enzyme induction by DDT was found.

Nicotinic acid-like substances

The interest in the metabolism of adipose tissue led Schwabe to work with his Göttingen assistant Arnold Hasselblatt , best known as an antidiabetic researcher, who completed his habilitation in 1962 (and later became Lendle's successor). In 1962, the inhibition of lipolysis - fat splitting - was discovered by nicotinic acid , an old medicinal substance for the treatment of disorders of lipid metabolism . Together, Hasselblatt and Schwabe characterized the principally similar but stronger inhibition by isoxazole and pyrazole derivatives. To be effective, the substances first had to be oxidized to carboxylic acids in the body . Schwabe's habilitation thesis comes from this material. Twenty-three years later he was to come back to the group of substances (see below).

Cyclic adenosine monophosphate

It has been known since the early 1960s that many hormone and neurotransmitter effects on fat and carbohydrate metabolism are mediated by cyclic adenosine monophosphate (cAMP) as a second messenger - second, intracellular messenger substance. cAMP is formed under catalysis by the enzyme adenylyl cyclase and broken down by the enzyme phosphodiesterase . With Hasselblatt, Schwabe examined whether the effect of insulin could also be mediated, with other co-authors, whether the effect of the isoxazole and pyrazole derivatives could also be mediated by cAMP. Meanwhile in Hanover, he made an observation that would shape his future. When isolated fat cells were suspended , the adrenaline-like substance isoprenaline , which acts on β-adrenoceptors and stimulates cAMP formation, increased lipolysis particularly strongly when the suspensions were diluted. Apparently the cells released a substance during the incubation which, if it accumulated, slowed down further lipolysis.

Adenosine

A year later the substance was identified as adenosine. Adenosine was also supported by the fact that the adenosine-degrading enzyme adenosine deaminase worked just like a dilution of the cell suspension, i.e. increased lipolysis. Methylxanthines such as caffeine and theophylline also promote lipolysis. The cause was presumed to be an inhibition of the cAMP-degrading phosphodiesterase. Now a new mechanism of action emerged: antagonism against the antilipolytic adenosine at its receptors in the cell membrane. The work has received a lot of attention. The fact that the pharmacologist Leopold Ther, who works at Farbwerke Hoechst AG , had already discovered an antagonism of methylxanthines against adenosine in 1957 (in the heart), Schwabe's group, like the adenosine research of the 1960s and 1970s in general, overlooked.

The methylxanthines have several primary effects, besides inhibiting phosphodiesterase and adenosine antagonism, they also inhibit the uptake of adenosine in cells. Schwabe and his hosts at the National Institutes of Health found a more selective inhibitor of phosphodiesterase, ZK 62711 or rolipram . The substance became a model substance for the inhibition of cAMP degradation. It was also developed as a drug, but not introduced into therapy.

Adenosine receptors and additional adenosine binding proteins (adenotines)

As a professor in Bonn and Heidelberg, Schwabe concentrated his research on the adenosine receptors . Initially, it was about their detection with the help of ligands , agonist ligands (receptor-activating substances) and antagonist ligands (receptor-blocking substances), including radioligands in particular . “That was all the rage in receptor research at the time: developing radioligands with high affinity and specificity and characterizing receptors through competition with other (unlabeled) ligands. If possible, define new subtypes through detailed analysis of curves. ”Then it was possible to study the occurrence of the receptors in the body, their molecular mechanism and their role in the action of drugs.

  • At the end of the 1970s it became known that there are at least two types of adenosine receptors, A 1 , initially also called R i , and A 2 , initially also called R a . To date (2015) the number has risen to four: A 1 , A 2a , A 2b and A 3 . Schwabe's group provided the decisive ligands and radioligands: 1980 tritium - ( 3 H-) labeled N 6 -phenylisopropyladenosine (PIA) as selective radioligands for A 1 receptors, 1984, already in Heidelberg, 3 H-labeled 5'-N- ethylcarboxamidoadenosine (NECA) as selective radioligands for A 2 receptors, 1985 125 I -labeled N 6 -p-hydroxyphenylisopropyladenosine (HPIA) and 1989 3 H-labeled 2-chloro-N 6 -cyclopentyladenosine (CCPA) again as selective radioligands for A. 1 receptors.
  • PIA, NECA, HPIA and CCPA activate adenosine receptors and are agonists. After a structure-activity analysis of xanthines as antagonists, the Heidelberg group combined two structural features that increase affinity and selectivity: “It is known that 1,3-dipropyl substitution of xanthines increases the affinity and selectivity for A 1 receptors. <...> The same happens with 8-cyclopentyl introduction. <...> If the two substitutions are additive, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) should be a highly refined and highly selective A 1 antagonist. ”This thought proved to be true, and the resulting article in Naunyn-Schmiedeberg's Archives of Pharmacology was Schwabe's most successful publication according to bibliometric criteria.
  • Thanks to the high specific activity of 125 I-HPIA, binding could also be detected in the heart. The A 1 receptors in the heart, more precisely in the atrioventricular node of the heart, mediate the only therapeutically exploited effect of adenosine, the interruption of AV node reentry tachycardias .
  • Receptors have to transmit the message of the agonists "docking" to them to the inside of the cell. In the case of the adenosine receptors, this occurs through guanosine triphosphate (GTP) -binding proteins, which split GTP: They are G-protein-coupled receptors . A “ternary complex” is formed from the agonist, receptor and G-protein. Adenylyl cyclase, for example, is then activated via the G protein (inhibited by other receptors) and the second messenger cAMP is increased (or decreased). Strong agonists do not require all receptors for maximum cell response; there is a "receptor reserve". According to the "allosteric model of the receptor-drug interaction", receptors exist in two conformations with which agonists and antagonists react differently. These general laws of signal translation to receptors also apply to adenosine receptors - studies of the 1980s and 1990s, with which the Heidelberg team “ dared to approach the revered journal Molecular Pharmacology ” for the first time .
  • Barbiturates such as pentobarbital inhibited the binding of 3 H-PIA to A 1 receptors in the brain of rats and the activation of these receptors. The inhibition has nothing to do with the known sleep-inducing effect, but could be responsible for the central nervous stimulating effects of some barbiturates.

The nicotinic acid receptor

After research into nicotinic acid and similar antilipolytic drugs in the 1960s, the topic was dormant around the world until around 1980 when, on the one hand, structure-effect analyzes led to new substances and, on the other hand, in Heidelberg - still at the time of Franz Gross - Günter Schultz's group advanced on the mechanism of action : Nicotinic acid inhibited adenylyl cyclase from adipose cells, apparently via a specific, namely G-protein-coupled receptor. About ten years later, Schwabe and his team identified the receptor through the binding of 3 H-nicotinic acid. Radioligand binding, adenylyl cyclase inhibition and GTP binding were in good agreement. "An important goal now is to clarify the amino acid sequence and the structure of the receptor protein," wrote Schwabe's group in 2001. The goal was already achieved two years later, notably again in Heidelberg, now by Stefan Offermanns' group. Today we know three variants of the nicotinic acid receptor, now also known as the “hydroxycarboxylic acid receptor”. Nicotinic acid reacts primarily with the HCA 2 or GPR109A receptor. It prevents the body's own 3-hydroxybutanoic acid from excessive fat loss, for example after prolonged fasting.

Drug safety and pharmacoeconomics

Human and animal organs always contain DDT from food or insecticide application. When Schwabe found that the higher the DDT concentration in adipose tissue, the less sleep induced pentobarbital in rats, he did not leave it with the finding (and its explanation, see above), but warned in 1964 that the acceleration of degradation could “become a disruptive factor Become a factor and represent a possible source of error when drugs are to be tested on such animals ”.

In 1977 he published in the German Medical Weekly the article "1000 deaths per year from over-the-counter bromocarbamide-containing sleeping pills in Germany?" The bromocarbamides or bromureides such as bromisoval , the oldest, were non- prescription sleeping pills dating back to the beginning of the 20th century . Since the Federal Statistical Office did not list deaths from bromocarbamides separately, Schwabe calculated them as the difference between “total number of deaths from sleeping pills and tranquilizers ” minus “number of deaths from individually listed substances such as barbiturates”: in 1974 the difference was greater than 1000 . Prescription requirements for bromocarbamides have repeatedly been called for. "So far, however, neither the drug commission of the German medical profession nor the Federal Health Office has backed this demand." In Switzerland and Austria, bromocarbamides are only available on prescription. "The Federal Ministry of Health should draw the conclusions from the facts at hand and introduce the prescription requirement <...>." Which soon happened.

Thirteen years apart, the two essays show Schwabe's commitment to application- related conclusions from his profession, namely drug safety and pharmacoeconomics - tasks that other pharmacologists did not necessarily find attractive.

From its founding in 1977 until its dissolution in 1992, he was a member of the “Transparency Commission” at the Federal Health Office, which was supposed to make the pharmaceutical market transparent in terms of pharmacological, therapeutic and price considerations. 1992 to 1995 and 2000 to 2003 he was an "institute for drug regulation, as Chairman of statutory health insurance " - each "institution" that twice during the life of this in its place in 2004 Institute for Quality and Efficiency in Health Care entered. Since 1981 he has been a member of the drug commission of the German medical profession.

Drug Prescription Report

By 1980, the Federation of proposed Local Health Insurance (AOK) Schwabe ago, together with the Scientific Institute of the AOK to develop a drug index, in which the medical drug regulations at the expense of health insurance statutory health insurance on the scope and pharmaco-therapeutic structure should be covered. In addition to Schwabe, the economist Dieter Paffrath (* 1949), then an employee and later head of the AOK's Scientific Institute, was to oversee the project. Support came from what was then the Federal Ministry for Research and Technology . For the first time in 1984, the data were evaluated on a yearly basis and published as a “ drug prescription report ”. The text on the back cover formulates the goal somewhat polemically: “What do German doctors prescribe their patients? For many years, drug consumption in the Federal Republic of Germany was a well-kept secret of the pharmaceutical industry. A research project does away with this situation, the current results of which are compiled in the 'Drug Prescription Report' 85 '. "

Since then, the “Drug Prescription Report” has been published annually. From 216 pages in the 1st edition of 1985 (evaluation of 1984) the report has grown to 1289 pages in the 30th edition of 2014 (evaluation of 2013). The evaluation of random samples became a full census in 2002. The drugs are always sorted according to indication groups, 18 groups from “ aldosterone antagonists” to “venous agents” in the 1st edition, 45 groups from “inhibitors of the renin-angiotensin system ” - against the alphabet because of the earlier name “ ACE inhibitors” and angiotensin receptor antagonists ”- to“ Dental Drug Prescriptions ”in the 30th edition. The indication groups and the individual remedies are commented on in terms of pharmacology and therapy - Schwabe is primarily responsible here.

The series shows how much drug therapy has changed due to new pharmacological-therapeutic findings and legislative measures. In 1984 " analgesics / anti-inflammatory drugs " followed by " antitussives / expectorants " were the most commonly prescribed drugs. In 2013, "analgesics" + " anti-inflammatory / anti-inflammatory drugs" (now listed separately) were the most commonly prescribed agents. The "antitussives / expectorants", however, now called "cough and cold preparations", had fallen to 17th place, and the "inhibitors of the renin-angiotensin system" took second place, which was still missing in 1984 - the first, Captopril , was introduced into therapy in 1979.

Title page of the 1997 edition
Page 554 of the 1997 edition

The “Medicines Ordinance Report '97” with its evaluation of 1996 caused the greatest stir. Some drug manufacturers had received a confidential working version. Numerous companies then sent warnings to Gustav Fischer Verlag. Bionorica , Dr. Willmar Schwabe and Strathmann GmbH & Co obtained an injunction from the Düsseldorf Regional Court , according to which the book was not allowed to appear. In particular, the plaintiffs turned against a table of 45 “controversial” drug groups, which could be replaced by cheaper ones with savings of around DM 4.5 million. Nevertheless, the report was published with blackening of the offending passages. The journal Arznei-Telegramm published the table the following year:

Table 46.5. Substitution of controversial drugs
group Controversial drug Substitution proposal
1 Anabolic steroids no
2 Analgesic combinations Paracetamol
10 Antihypotonic drugs not medicinal
18th Expectorants non-medicinal (liquid)
42 Venous medication Compression therapy
45 Xanthine combinations Theophylline

The preliminary injunction was later lifted by the cartel panel of the Düsseldorf Higher Regional Court, and the “Drug Ordinance Report 1998” appeared unmolested.

The section on Schwabe's research topic nicotinic acid in the “Drug Ordinance Report 2014” ends: “With the withdrawal of Tredaptive from the market, no nicotinic acid preparation is available in Germany.”

Medicinal prescriptions in Europe

Together with colleagues from England, France and Italy, Schwabe has examined the prescriptions of statins used in lipid metabolism disorders in several European countries. Within large groups of scientists, he explored the role of supply and demand in medical prescriptions.

Others

From 1977 to 1999 Schwabe was editor or consultant editor of Naunyn-Schmiedeberg's Archives of Pharmacology , the world's oldest pharmacological journal in existence. From 2007 to the final report in 2009, he was a member of the expert commission to investigate doping allegations against doctors in the sports medicine department of the Freiburg University Hospital .

Habilitations

The following scientists have completed their habilitation at the time of Schwabe's full professorship in Heidelberg:

recognition

In 2005 Schwabe was awarded the Federal Cross of Merit.

literature

  • Jürgen Lindner, Heinz Lüllmann : Pharmacological institutes and biographies of their directors. Editio Cantor Verlag, Aulendorf 1996.
  • Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004. ISBN 3-85093-180-3 .

References and comments

  1. ↑ a b c Martin Lohse: Autobiography. In: Athineos Philippu: History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Volume IV. Autobiographies. Berenkamp-Verlag, Innsbruck 2014. ISBN 3-85093-325-3 , pp. 439-465.
  2. ↑ G. Engelhardt, U. Schwabe: About a 5-hydroxytryptamine release under the anaphylactic reaction of the guinea pig . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . tape 239 , no. 2 , 1960, p. 160-183 , doi : 10.1007 / BF00249422 .
  3. ↑ G. Gerboth, U. Schwabe: Influence of tissue-stored DDT on the effect of pharmaceuticals . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . tape 246 , no. 6 , 1964, pp. 469-483 , doi : 10.1007 / BF00246300 .
  4. ↑ a b c Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 358 , no. 1 , 1998, p. 1-109 , doi : 10.1007 / PL00005229 .
  5. ↑ Aktories and others 2013, pp. 581–582.
  6. ↑ U. Schwabe, E. Kerstein, A. Hasselblatt: Inhibition of lipolysis in adipose tissue by methylisoxazole carboxylic acids . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . tape 260 , no. 1 , 1968, p. 1-15 , doi : 10.1007 / BF00545003 .
  7. ↑ B. Müller-Oerlinghausen, U. Schwabe, A. Hasselblatt, FH Schmidt: Activity of 3 ', 5'-AMP phosphodiesterase in liver and adipose tissue of normal and diabetic rats . In: Life Sciences . tape 7 , no. 12 , 1968, p. 593-598 , doi : 10.1016 / 0024-3205 (68) 90080-5 .
  8. ↑ U. Schwabe, R. Ebert: Different effects of lipolytic hormones and phosphodiesterase inhibitors on cyclic 3 ', 5'-AMP levels in isolated fat cells . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 274 , no. 3 , 1972, p. 287-298 , doi : 10.1007 / BF00501938 .
  9. ↑ U. Schwabe, R. Ebert, HC Erbler: Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3 ′, 5′-AMP levels and lipolysis . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 276 , no. 2 , 1973, p. 133-148 , doi : 10.1007 / BF00501186 .
  10. ^ R. Ebert, U. Schwabe: Studies on the antilipolytic effect of adenosine and related compounds in isolated fat cells . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 278 , no. 3 , 1973, p. 247-259 , doi : 10.1007 / BF00500286 .
  11. ↑ U. Schwabe, R. Ebert: Stimulation of cyclic adenosine 3 ', 5'-monophosphate accumulation and lipolysis in fat cells by adenosine deaminase . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 282 , no. 1 , 1974, p. 33-44 , doi : 10.1007 / BF00647401 .
  12. ↑ Max Lafontan: Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways . In: American Journal of Physiology - Cell Physiology . tape 302 , no. 2 , 2012, p. C327-C359 , doi : 10.1152 / ajpcell.00168.2011 .
  13. ↑ L. Ther, R. Muschawek, J. Hergott: Antagonism between adenosine and methyl xanthines in the conduction system of the heart . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . tape 231 , no. 6 , 1957, pp. 586-590 , doi : 10.1007 / BF00258995 .
  14. ↑ U. Schwabe, M. Miyake, Y. Ohga, JW Daly: - (3-Cyclopentyloxy-4-methoxyphenyl) -2-pyrrolidone (ZK 62711): a potent inhibitor of adenosine cyclic 3 ', 5'-monophosphate phosphodiesterases in homogenates and tissue slices from rat brain . In: Molecular Pharmacology . tape 12 , no. 6 , 1976, p. 900-910 , PMID 187926 .
  15. ↑ Sandra Marie Schaal, Maneesh Sen Garg, Mousumi Ghosh, Lilie Lovera, Michael Lopez, Monal Patel, Jack Louro, Samik Patel, Luis Tuesta, Wai-Man Chan, Damien Daniel Pearse: The therapeutic profile of rolipram, PDE target and mechanism of action as a neuroprotectant following spinal cord injury . In: PLOS ONE . tape 7 , no. 9 , 2012, p. e43634 , doi : 10.1371 / journal.pone.0043634 .
  16. ^ Simplified, redrawn from A. Lorenzen and U. Schwabe: P1 receptors. In: MP Abbracchio and M. Williams (Eds.): Purinergic and Pyrimidinergic Signaling I. Handbook of Experimental Pharmacology 151 / I.
  17. ↑ Review article by Ulrich Schwabe with co-authors: Bertil B. Fredholm, Maria P. Abbracchio, Geoffrey Burnstock, George G. Dubyak, T. Kendall Harden, Kenneth A. Jacobson, Ulrich Schwabe, Michael Williams: Towards a revised nomenclature for P1 and P2 receptors . In: Trends in Pharmacological Sciences . tape 18 , no. 3 , 1997, p. 79-82 , doi : 10.1016 / S0165-6147 (96) 01038-3 . and A. Lorenzen and U. Schwabe: P1 receptors. In: MP Abbracchio and M. Williams (Eds.): Purinergic and Pyrimidinergic Signaling I. Handbook of Experimental Pharmacology 151 / I. Springer-Verlag , Berlin, Heidelberg, New York 2001. ISBN 3-540-67849-2 , pp. 19-45.
  18. ↑ U. Schwabe, T. Trost: Characterization of adenosine receptors in rat brain by ( -) [ 3 H] N 6 -phenylisopropyladenosine . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 313 , no. 3 , 1980, p. 179-187 , doi : 10.1007 / BF00505731 .
  19. ↑ Thomas Trost, Ulrich Schwabe: Adenosine receptors in fat cells. Identification by (-) - N 6 - [ 3 H] phenylisopropyladenosine binding . In: Molecular Pharmacology . tape 19 , no. 2 , 1981, p. 228-235 , PMID 6262616 .
  20. ↑ E. Hüttemann, D. Ukena, V. Lenschow, U. Schwabe: R a Adenosine receptors in human platelets. Characterization by 5'-N-ethylcarboxamido [ 3 H] adenosine binding in relation to adenylate cyclase activity . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 325 , no. 3 , 1984, pp. 262-233 , doi : 10.1007 / BF00495948 .
  21. ↑ Martin J. Lohse, Dieter Ukena, Ulrich Schwabe: Demonstration of R i -type adenosine receptors in bovine myocardium by radioligand binding . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 328 , no. 3 , 1985, pp. 310-316 , doi : 10.1007 / BF00515559 .
  22. ↑ Martin J. Lohse, Karl-Norbert Klotz, Ulrich Schwabe, Gloria Cristalli, Sauro Vittori, Mario Grifantini: 2-Chloro-N 6 -cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 337 , no. 6 , 1988, pp. 687-698 , doi : 10.1007 / BF00175797 .
  23. ↑ Karl-Norbert Klotz, Martin J. Lohse, Ulrich Schwabe, Gloria Cristalli, Sauro Vittori, Mario Grifantini: 2-Chloro-N 6 - [ 3 H] cyclopentyladenosine ([ 3 H] CCPA) - a high affinity agonist radioligand for A 1 adenosine receptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 340 , no. 6 , 1989, pp. 679-683 , doi : 10.1007 / BF00717744 .
  24. ↑ U. Schwabe, D. Ukena, MJ Lohse: Xanthine derivatives as antagonists at A 1 and A 2 adenosine receptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 330 , no. 3 , 1985, pp. 212-221 , doi : 10.1007 / BF00572436 .
  25. ↑ Martin J. Lohse, Karl-Norbert Klotz, Jutta Lindenborn-Fotinos, Martin Reddington, Ulrich Schwabe, Ray A. Olsson: 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) - a selective high affinity antagonist radioligand for A 1 adenosine receptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 336 , no. 2 , 1987, pp. 204-210 , doi : 10.1007 / BF00165806 .
  26. ↑ Dirk Martens, Martin J. Lohse, Bernhard Rauch, Ulrich Schwabe: Pharmacological characterization of A 1 adenosine receptors in isolated rat ventricular myocytes . In: Naunyn-Schmiedeberg's Archives of Pharmacology . tape 336 , no. 3 , 1987, pp. 342-348 , doi : 10.1007 / BF00172688 .
  27. ↑ Aktories and others 2013, p. 397.
  28. ↑ Aktories and others 2013, pp. 4–24.
  29. ↑ Martin J. Lohse, Volker Lenschow, Ulrich Schwabe: Two affinity states of R i adenosine receptors in brain slices. Analysis of guanine nucleotide and temperature effects on radioligand binding . In: Molecular Pharmacology . tape 26 , no. 1 , 1984, p. 1-9 , PMID 6087114 .
  30. ↑ Martin J. Lohse, Karl-Norbert Klotz, Ulrich Schwabe: Agonist photoaffinity labeling of A 1 adenosine receptors: persistent activation reveals spare receptors . In: Molecular Pharmacology . tape 30 , no. 4 , 1986, pp. 403-409 , PMID 3020390 .
  31. ↑ Anna Lorenzen, Martin Fuss, Heidrun Vogt, Ulrich Schwabe: Measurement of guanine nucleotide-binding protein activation by A 1 adenosine receptor agonists in bovine brain membranes: stimulation of guanosine-5'-O- (3- [ 35 S] thio) triphosphate binding. In: Molecular Pharmacology . tape 44 , no. 1 , 1993, p. 115-123 , PMID 8341267 .
  32. ↑ Anna Lorenzen, Laura Guerra, Heidrun Vogt, Ulrich Schwabe: Interaction of full and partial agonists of the A 1 adenosine receptor with receptor / G protein complexes in rat brain membranes . In: Molecular Pharmacology . tape 49 , no. 5 , 1996, pp. 915-926 , PMID 8622642 .
  33. ↑ MJ Lohse, KN Klotz, KH Jakobs, U. Schwabe: Barbiturates are selective antagonists at A 1 adenosine receptors . In: Journal of Neurochemistry . tape 45 , no. 6 , 1985, pp. 1761-1770 , doi : 10.1111 / j.1471-4159.1985.tb10532.x .
  34. ↑ K. Aktories, KH Jakobs, G. Schultz: Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone-like manner . In: FEBS Letters . tape 115 , no. 1 , 1980, p. 11-14 , doi : 10.1016 / 0014-5793 (80) 80715-0 .
  35. ↑ a b Anna Lorenzen, Christina Stannek, Heidrun Lang, Viktor Adrianov, Ivars Kalvinsh, Ulrich Schwabe: Characterization of a G protein-coupled receptor for nicotinic acid . In: Molecular Pharmacology . tape 59 , no. 2 , 2001, p. 349-357 , PMID 11160872 .
  36. ↑ Anna Lorenzen, Christina Stannek, Anja Burmeister, Ivars Kalvinsh, Ulrich Schwabe: G protein-coupled receptor for nicotinic acid in mouse macrophages . In: Biochemical Pharmacology . tape 64 , no. 4 , 2002, p. 645-648 , doi : 10.1016 / S0006-2952 (02) 01220-0 .
  37. ↑ Sorin Tunaru, Jukka Kero, Annette Schaub, Christian Wufka, Andree Blaukat, Klaus Pfeffer, Stefan Offermanns: PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect . In: Nature Medicine . tape 9 , 2003, p. 352-355 , doi : 10.1038 / nm824 .
  38. ^ Stefan Offermanns, Steven L. Colletti, Timothy W. Lovenberg, Graeme Semple, Alan Wise, Adriaan P. IJzerman: International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B) . In: Pharmacological Reviews . tape 63 , no. 2 , 2011, p. 269-290 , doi : 10.1124 / pr.110.003301 .
  39. ↑ U. Schwabe: DDT storage in the keeping of laboratory animals as a possible source of errors in drug testing . In: drug research . tape 14 , no. 11 , 1964, pp. 1265-1266 .
  40. ↑ U. Schwabe: 1000 deaths per year from over-the-counter bromocarbamide-containing sleeping pills in Germany? In: German Medical Weekly . tape 102 , no. 24 , 1977, pp. 885-888 , doi : 10.1055 / s-0028-1104982 .
  41. ↑ Entry on Bromureide. In: Römpp Online . Georg Thieme Verlag, accessed on February 17, 2015.
  42. ↑ The pharmacologist Fred Lembeck on the work of Werner Koll , a generation older , who was similarly committed to Schwabe : “Achievements that he achieved in the difficult area between our subject and the public: <...> ready, at any time between subject and authorities, between To convey science, the medical association and industry, he was just taking on the tasks that others found too laborious and ungrateful. ”Fred Lembeck: Werner Koll. Welcome address by the chairman . In: Naunyn-Schmiedebergs Archive for Pharmacology . tape 264 , no. 3 , 1969, p. 187-193, here pp. 188-189 , doi : 10.1007 / BF02431407 .
  43. ↑ Ulrich Schwabe, Dieter Paffrath (Ed.): “Drug Ordinance Report '85.” Gustav Fischer Verlag , Stuttgart, New York 1985. ISBN 3-437-11038-1 .
  44. ↑ Ulrich Schwabe, Dieter Paffrath (Ed.): “Drug Ordinance Report 2014.” Springer-Verlag, Berlin, Heidelberg 2014. ISBN 978-3-662-43486-4 .
  45. ^ AB Atkinson, JIS Robertson: Captopril in the treatment of clinical hypertension and cardiac failure . In: The Lancet . tape 314 , no. 8147 , 1979, pp. 836-839 , doi : 10.1016 / S0140-6736 (79) 92186-X .
  46. ↑ “No - this is not a work of the late Mondrian , but that of the contemporary pharmaceutical industry. And this is what many pages of the 'Medicinal Prescription Report' 97 'look like. It did appear recently after a few manufacturers of drugs without proven efficacy and harmlessness temporarily banned long passages. Above all, the entire chapter on particularly controversial drugs was blacked out, such as those that are supposed to be good for veins or the prostate, which supposedly promote blood circulation or degummed necks. "Rosemarie Stein in Der Tagesspiegel of January 18, 1998.
  47. ↑ Ulrich Schwabe, Dieter Paffrath (Ed.): Drug Ordinance Report '97. Gustav Fischer Verlag, Stuttgart, Jena, Lübeck, Ulm 1997. ISBN 3-437-21091-2 .
  48. ↑ Heike Korzilius: drug prescription report ´97 stopped: judgment causes a stir . In: Deutsches Ärzteblatt . tape 94 , no. 40 , 1997, pp. A-2540 . Digitized. Retrieved March 1, 2015.
  49. ↑ Controversial Medicines. In: Arznei-Telegram 1998. Digitized. Retrieved February 21, 2015.
  50. ↑ Combination preparation of nicotinic acid and a prostaglandin D 2 antagonist.
  51. ↑ Tom Walley, Pietro Folino-Gallo, Ulrich Schwabe, Eric van Ganse on behalf of the EuroMedStat group: Variations and increase in use of statins across Europe: data from administrative databases . In: British Medical Journal . tape 328 , no. 7436 , 2004, pp. 385-386 , doi : 10.1136 / bmj.328.7436.385 .
  52. ^ Brian Godman, ... Ulrich Schwabe ... 23 authors: Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilization: changes seen and global implications . In: Expert Review of Pharmacoeconomics & Outcomes Research . tape 10 , no. 6 , 2010, p. 707-722 , doi : 10.1586 / erp.10.72 .
  53. ↑ Brian Goldman, ... Ulrich Schwabe ... 24 Authors: Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications . In: Frontiers in Pharmacology . tape 5 , 2014, doi : 10.3389 / fphar.2014.00106 .
  54. ↑ Final report digitized . Retrieved March 1, 2015.
personal data
SURNAME Schwabe, Ulrich
BRIEF DESCRIPTION German doctor and pharmacologist
DATE OF BIRTH July 19, 1935
PLACE OF BIRTH Goettingen