Heinrich Dreser

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Dreser 1897

Heinrich Dreser (born October 1, 1860 in Darmstadt , † December 21, 1924 in Zurich ) was a German doctor and pharmacologist . He headed university institutes and the pharmacological laboratory of Bayer AG , at that time “paint factories in front of me. Friedr. Bayer & Co. ”, in Elberfeld . There he and the chemists Arthur Eichengrün and Felix Hoffmann discovered diacetylmorphine ( Heroin ® ) and acetylsalicylic acid ( Aspirin ® ).

Heinrich Dreser (2nd from right) in the pharmacological laboratory at Bayer 1897.

Life

The main sources are the obituaries of his academic colleague Hans Horst Meyer and his industrial colleague Ernst Lomnitz. Dreser studied medicine in Heidelberg and was awarded a doctorate there in 1884 with a thesis on the chemistry of retinal rods. med. PhD . He then worked at the Physiological Institute of the Silesian Friedrich Wilhelms University in Breslau with Rudolf Heidenhain , at the Pharmacological Institute of the Kaiser Wilhelm University in Strasbourg with Oswald Schmiedeberg and at the Physiological-Chemical Institute of the Eberhard Karls University in Tübingen with Gustav von Hüfner . In Tübingen he completed his habilitation in pharmacology and toxicology in 1891 . He then went to Carl Binz at the Pharmacological Institute of the Rheinische Friedrich-Wilhelms-Universität Bonn , from where he was appointed as successor to Wilhelm Marmé (1832-1897) to the chair of pharmacology at the Georg-August-Universität Göttingen , initially only as an associate professor . That may have been the reason why, on April 1, 1897, he headed the pharmacological laboratory of the "paint factories" founded in 1890. Friedr. Bayer & Co. ”in Elberfeld.

After seventeen years with Bayer in 1914, as Hans Horst Meyer writes, “for reasons unknown to me, he turned to Liège , where an experimental therapeutic laboratory was open to him to collaborate. A few months later the war broke out and Dreser, like all Germans, had to leave Belgium with his wife in a hurry, leaving his belongings behind. ”He received a voluntary work at the Institute for Biochemistry of the Medical Academy Düsseldorf , presumably financially independent thanks to his royalties from Bayer Professorship for pharmacology, from which an independent pharmacological institute emerged in 1923. In October 1924 he began experiments at the Pharmacological Institute of the University of Zurich , headed by Max Cloetta (1868–1940), but died a few weeks later. He was well educated, played the violin, viola and cello, while being closed off, often sarcastic or ironic in conversation, and little inclined to deal with people except in scientific exchange.

Research: at universities

According to Hans Horst Meyer, Dreser's achievement consists primarily in the quantification of pharmacological observations; he “sought to set up the investigation methodology and to adapt it to the respective accusation in such a way that it had to lead to a numerically representable result. This not only requires mathematical and physical dexterity, but also a significant degree of inventive skill. ”He proved both when he devised a method for quantifying the work of isolated frog hearts in Schmiedeberg's laboratory in Strasbourg. Also from Strasbourg comes a work on lobeline , an alkaloid from the North American Loblia inflata . The plant was “a main remedy of American quackery, the 'medical botanists', who used Lobelia as a panacea for a wide variety of diseases. Such extensive use of heroic means, as popular medicine often likes, has turned American and English literature into a treasure trove of 'medicinal' poisoning by Lobelia inflata. ... The fact that the drug causes vomiting very often seems to have saved the lives of many patients; the Lobelia acted as an 'antidote to itself' ”. Dreser recognized “that the alkaloid lobelin is a respiratory poison” and stimulated breathing if the dosage was not too high. Again he devised a quantification, this time of the breath volume ; it became a standard practice. Lobeline was later used therapeutically as a breath stimulant. In Tübingen, Dreser used the lowering of the freezing point to determine the urinary content of dissolved substances and to study kidney activity. Since his time in Bonn and until his last weeks in Zurich, he dealt with the dangers of inhalation anesthetics , warned against bromoethane , which is no longer used today, and constructed anesthesia machines.

Research: at Bayer

In Elberfeld, later Leverkusen, under Dreser and the Bayer director Carl Duisberg, a large pharmacological laboratory was built in addition to the pharmaceutical and chemical laboratories, probably the oldest pharmacological industrial laboratory. In 1910, Dreser also set up his own laboratory for antimicrobial chemotherapy, from which such famous substances as suramin ( Germanin ® , 1924), mepacrine ( Atebrin ® , 1930) and the first sulfonamide, sulfamidochrysoidin ( Prontosil ® , 1935) emerged. Ernst Lomnitz judged: “ In the history of the pharmaceutical department of the paint factories, the Dreser era means vorm. Friedr. Bayer & Co. set a milestone, because it proved to the medical world that work was being carried out on this site seriously and according to strictly scientific criteria, and the clinicians were reassuringly aware that they had tested the animal experiments they were given and found that they could be used were allowed to confidently use the preparations found at the bedside. "

Dreser carried as pharmacologist to introduce two of Oswald Schmiedeberg excited carbamic acid ester as a sleep aid in, namely Hedonal ® and carbromal ( adalin ® ). They shield the nerve cells, he said, from the outside world. "This' inner calm '' of the central nervous system makes healthy sleep possible, or as Shakespeare has Macbeth say: 'holy sleep, the main course at the table of life'." However, hedonal and carbromal are like almost all clearly acting sleeping pills apart from the benzodiazepines disappeared from therapy due to numerous fatal poisonings. This also applies to the barbiturate phenobarbital ( Luminal ® ) used as a sleeping aid, which Heinrich Hörlein synthesized in 1911 in Bayer's pharmaceutical and chemical laboratories. In the treatment of epilepsy , however, phenobarbital has remained one of the most important drugs since Alfred Hauptmann discovered it for this indication in 1912.

Dreser used his experience in kidney physiology to develop the theophylline preparation Theocin ® as a diuretic . He recognized that it had a stronger effect than its close relatives caffeine and theobromine and concluded: “In any case, after these diuresis experiments in healthy people, it is to be expected that the theocine, due to its pronounced eliminatory functions, will not only act against water, but also against salts, ... also in Eliminate the same constituents that bind the water to the pathological condition of dropsy and thereby make the water bound to these electrolytes mobile. " Oskar Minkowski , co-discoverer of the role of the pancreas in the metabolism of carbohydrates , agreed:" Through an ingenious combination of physico-chemical methods by Determined the ratio of the lowering of the freezing point to the electrical conductivity in the urine, Dreser came to the conclusion that theophylline not only increases the urinary water, but also increases the total number of molecules excreted per minute, especially because electrolyte initially e (salts) are transported out to an even greater extent than non-electrolytes. ”Dreser and Minkowski's insight is still valid today: A negative fluid balance“ only succeeds if the excretion of salts is increased, which in turn bind water osmotically ”.

Dreser also contributed to the introduction of the non-bitter-tasting quinine derivative Aristochin ® and the colloidal silver-albumin compound Protargol ® . Protargol has been extremely successful for external use, especially for gonorrhea . The pharmaceutical-chemical inventor was Arthur Eichengrün. His royalties for Protargol in 1907 alone amounted to 13,309 marks - at that time a teacher earned 1200 to 1500 marks per year. In order to quantify the astringent effect of silver compounds, Dreser measured the extensibility of isolated lungs of frogs - another method of his own.

If these drugs were important in the Dreser era and are still important today in the case of the phenobarbital, diacetylmorphine or heroin and acetylsalicylic acid or aspirin were spectacular in the true sense of the word.

Research: Heroin and Aspirin

According to Michael de Ridder, the inventions of heroin and aspirin show remarkable similarities:

  • Both were obtained by acetylation . Acetylation with acetic anhydride to obtain or “refine” drugs or natural substances has existed long before. Acetylation turned the aniline into the fever lowering acetanilide ( Antifebrin ® ) in 1886 and in 1887 - at Bayer - the fever lowering Phenacetin ® from the p-phenetidine . So it was just in time that before Dr Drers took up his post in 1897 in the pharmaceutical and chemical department, diacetylmorphine, which relieves pain and coughs, had been produced from morphine . One year after diacetylmorphine, the first production of pure acetylsalicylic acid followed.
  • Bayer was no longer able to have both synthetic routes protected by patent, as they were already used by CRA Wright (1874; morphine) and H. v. Gilm (1859; acetylsalicylic acid) had been shown. The trademark rights heroin and aspirin were registered for both substances .
  • In both cases, Dreser's pharmacological-preclinical studies consisted of comparisons with standard substances, one with codeine and the other with salicylic acid . In both cases, Dreser drew fundamentally wrong conclusions when the findings were probably correct.

After their introduction, however, the paths of the two substances could not be more opposed. Heroin soon sparked heated controversy. It has not made significant progress in basic research, but has become the most abused opioid , producing around 396 tonnes worldwide in 2010 and accounting for most of drug morbidity and mortality in the European Union . There was little dispute about acetylsalicylic acid. Through the discovery of its mechanism of action - inhibition of the biosynthesis of prostaglandins - it has extremely fertilized basic research, became the most successful drug of all time and is now the most widely used, with an annual production of around 50,000 tons worldwide.

At Bayer, Dreser was particularly valued. Carl Duisberg wrote in 1920: "The invention [of aspirin] culminated in the discovery of the excellent pharmacological properties that Dreser found in our laboratory." Dreser only obtained Tantienem for heroin and aspirin from the paint factories. In the anniversary book Milestones - 125 Years of Bayer 1863–1988 , only Hoffmann and Dreser are named as inventors in the chapter Aspirin - Medicines ' for all eternity' (and heroin is eloquently kept silent).

  • Introductory publications

  • Dreser's pharmacological conception of heroin

  • Floret's first clinical report on heroin

  • Dreser's pharmacological conception of aspirin

  • Witthauser's first clinical report on aspirin

heroin

Dreser's first two publications on heroin appeared as early as 1898, one, more for experimental pharmacologists, in the archive for the entire physiology of humans and animals, the other, more for clinicians, in the therapeutic monthly books . In it he compared codeine , a methyl morphine, which is popular as an antitussive but has hardly been processed scientifically , with three other morphine derivatives, one of which is “the di-acetic acid ester of morphine, which the paint factories previously used. Friedrich Bayer & Co. zu Elberfeld protected under the name: 'Heroin' ”.

"When comparing the already effective administration with the fatal administration in rabbits ... there was a marked difference in favor of heroin": Heroin dampened breathing more than codeine and had a greater therapeutic range . Based on his spirometric expertise from the lobelin examination, Dreser checked further. Heroin lowered the respiratory rate, but increased the tidal volume: "an economic change in the breaths ... in such a way that heroin beneficially increases the performance of the individual breath in each of the directions examined". The sensitivity of the respiratory center to carbon dioxide and oxygen deficiency remained the same, the oxygen consumption of the body was reduced, and that without "alteration of consciousness". “The measurement of the oxygen consumption also explains to us that the organism's need for oxygen is curatively reduced by immobilizing superfluous muscle movements, and the doctor also seeks to protect the lungs by prohibiting unnecessary speech. The reduction in the gas exchange to be performed by the lungs also protects the organ, and in this respect heroin has a more intense and lasting effect than codeine. "Finally:" As a medicine against coughs, I have found heroin to be very effective in humans at <10 mg>, after the communication of Dr. For many people, Floret already suffices as a single dose of 5 milligrams with exactly the same indications under which <30 mg> codeine phosphate are ordained. "

The report by Theobald Floret, company doctor at Bayer, followed immediately in the Therapeutic Monthly Bulletins . "The heroin, which I have prescribed for about half a year in the polyclinic of the paint factories in Elberfeld ... turned out to be an extremely useful, prompt and reliable means of combating coughing and coughing as well as chest pain, primarily in the case of inflammation, especially in the catarrhal of the upper and lower respiratory tract ( angina , pharyngitis , tracheitis , bronchitis ), both in the acute and more chronic forms. About 60 patients of this type treated by me with the preparation agreed to me that after ingesting the powder (heroin ) would have felt an immediate improvement in the tormenting cough, that the chest pain and the stabbing in the side - if such complaints existed - would have subsided. "Dr., the powders you gave me are very good." ... One of these patients explained to me that so far no medicine had done him as well as my powder. ... Heroin also served me very well in the treatment of pulmonary tuberculosis. ... Unfavorable side effects do not seem to adhere to the preparation. ... A habit of getting used to it does not seem to occur. "

The articles sparked a flood of publications, some approving, some rejecting, 13 in the second half of 1899 alone in the Munich medical weekly . The sharpest critic was Dreser's colleague from Halle, Erich Harnack .

“After all that we know so far about heroin from animals and humans, I am of the opinion that the transfer of the drug to the practice was premature and that an extremely dangerous poison was thus given into the hand of the unsuspecting practitioner , in respect of which sufficient caution cannot be urged. I wholeheartedly acknowledge that Dreser acted in good faith that his in-depth rabbit experimental study was sufficient to 'conscientiously recommend therapeutic advice' for the drug, but I believe that Dreser failed to pay enough attention to two fundamental facts. ”First Dreser trusted too much the transferability of animal experimental findings to humans, and secondly, underestimated the possibility of increased toxicity through acetylation. “The general public” warned Harnack: “The product has already been brought into the hands of laypeople and recommended in alpine clubs to use it to relieve respiratory problems when mountaineering. ... Here it says: Principiis obsta, otherwise we will soon have to register a new form of chronic medicinal poisoning, namely heroinism! Doctors and laypeople have some respect for morphine; Replacing it with heroin means driving out the devil with Beelzebub, just as morphinism was 'replaced' by the more dangerous cocainism. ”Heroin is“ one of the most poisonous substances in our medicinal treasure trove. You have to let the authors of this 'new' remedy choose the right name for it; it really belongs under the 'Heroica' . "

Dreser replied no less polemically to the Munich medical weekly in the same year , and Harnack wrote another reply in the same year. In the end, Harnack was right in his warning. Although called Bayer in 1905 among the numerous indications and the morphine withdrawal, but Paul Trendelenburg , one of the most well-known pharmacologist of his time, wrote in his Fundamentals of general and specific drug regulations in 1926 shortly: "Heroin ... should because of the stronger side effects and the high risk of Heroinismus not be given . "

Dreser's mistake was to see heroin as an opioid with a more favorable spectrum of activity than morphine and codeine. Heroin, however, has the typical effects of opioids, modified by its special pharmacokinetics : thanks to its high lipophilicity , it quickly penetrates the brain and is quickly hydrolyzed to 6-monoacetylmorphine , which then strongly activates µ-opioid receptors .

  • Art Nouveau

  • Vials for heroin, shortly after 1900

  • Advertisement, around 1905

  • Bottle for aspirin, around 1900

aspirin

Salicylic acid was an established antipyretic, pain reliever and anti-inflammatory drug. Dreser introduces his first report in the archive for the entire physiology of man and animals : “In many disease states attributed to 'colds', the use of sodium salicylic acid would certainly be much more popular if it weren't for its disgustingly sweet taste, which is only bad can be corrected, provokes such aversion. Here, pharmaceutical chemistry may be able to synthetically produce a preparation that avoids the unpleasant phenomena in the 'first ways', which in addition to the disgusting taste also includes the annoyance of the stomach. After absorption, the effective salicylic acid should split off from the new product as quickly as possible. ”Better taste, better gastric tolerance and rapid release of salicylic acid were the goals of the research trio at Bayer.

In fact, with acetylsalicylic acid, the unpleasant taste was replaced by a "pleasant, tart, sour taste".

In order to detect local tissue damage, Dreser applied acetylsalicylic acid and salicylic acid to the transparent swim fins of small fish. They quickly became opaque on contact with salicylic acid, less on contact with acetylsalicylic acid. The latter was probably better gastric tolerated.

Finally, as hoped, acetylsalicylic acid disintegrated more or less rapidly into salicylic and acetic acid, depending on the solution conditions. “With the easy cleavage of aspirin ... its metabolic behavior is also consistent. Already 22 minutes after taking 1 g of aspirin sodium, I received the salicylic reaction directly in my urine due to iron chloride . So the acetyl group had already been at least partially split off. ... The excretion was, as can be deduced from the disappearance of the salicylic reaction from the urine, mostly ended 12 hours after taking the aspirin. "

As with heroin, Drister's pharmacological presentation was clinically flanked. Kurth Witthauer, doctor at the Diakonissenhaus in Halle, wrote after experience with fifty patients: “Salicylic is and will remain the best of the remedies known to date for rheumatism and related diseases. ... If the salicylic had no bad effect on the digestive organs and if it did not cause the annoying ringing in the ears so often, if it did not taste so disgusting, then its influence on the diseases mentioned could be called almost ideal. I do not think I am too optimistic when I assert that we have come closer to this ideal with the use of aspirin. ... The patients always took it gladly and without reluctance, and those who had already received other salicylic preparations praised the much more pleasant taste. ... I can generally add that the sick were unwilling when we had to stop the aspirin because of a lack of supplies. ... The remedy never failed to influence the pain, swelling and fever and never had an unfavorable effect on the heart and stomach, even in the severely ill. It was amazing how well the appetite was maintained even in patients who had to take aspirin for a long time. "

100 pfennig postage stamp from 1990 with the structural formula of acetylsalicylic acid

Acetylsalicylic acid has maintained its place as a medicinal substance, even expanded it. Paul Trendelenburg wrote in his drug prescription book in 1926 (see above): “The introduction of the acetic acid ester of salicylic acid (Asprin, by Dreser 1899) brought about an important step forward. ... Since the introduction of the acetyl ester (aspirin), salicylic acid has been used much less often to lower the increased body temperature associated with infectious diseases. ... The analgesic effect, which, as with almost all antipyretic agents, is also inherent in salicylic acid, is so much more pronounced in acetylsalicylic acid that salicylic acid is rarely used in neuralgia and migraines . ... Because of its less irritating effect on the stomach, [acetylsalicylic acid over salicylic acid] is preferable. " Thomas Mann mentions acetylsalicylic acid 75 times in his diaries from 1918 to 1955 (for example, on December 10, 1918" afternoon aspirin, to which I react wonderfully "; heroin once, on April 1, 1943 "Sore throat very annoying. Cough reduced by heroin. Nice, warm weather. ... Rommel continues to defend himself in Tunisia") with a total of 1189 remedies mentioned. The list of essential drugs of the World Health Organization contains acetylsalicylic acid in its 17th edition from March 2011 three times: as a non-opioid analgesic for mild pain and fever, as a remedy for an acute migraine attack and as a platelet aggregation inhibitor for the prophylaxis against stroke and heart attack .

But here, too, Dreser was fundamentally wrong. As can be seen from his introduction, he assumed and never questioned this assumption that acetylsalicylic acid worked by hydrolysis to salicylic acid, that the latter was the actual active ingredient, while acetylic acid, on the other hand, was a prodrug . In his story of aspirin , the English pharmacologist Henry Oswald Jackson Collier (1912–1983), who carried out relevant research himself, showed how the error was corrected and productive .

  • In the beginning there was the effectiveness of the willow bark and the salicylic acid it contained.
  • In 1897, Felix Hoffmann, perhaps at the suggestion of Arthur Eichengrün, developed the first industrially usable acetylsalicylic acid synthesis, and Dreser tested the substance pharmacologically.
  • In the years that followed, it was observed that acetylsalicylic acid was sometimes stronger than salicylic acid and therefore not on the way over it. This became clear since 1959, for example in the case of platelet aggregation , which was strongly inhibited by acetylsalicylic acid but not inhibited by salicylic acid.
  • In the 1960s, Collier understood fever, pain and inflammation as defensive reactions of the body and suspected that acetylsalicylic acid and analogous non-steroidal anti-inflammatory drugs intervened in the development of these defensive reactions .
  • In 1971 the British pharmacologist John Robert Vane found that aspirin and other non-steroidal anti-inflammatory drugs inhibited the biosynthesis of prostaglandins, for which he was awarded the Nobel Prize in Physiology or Medicine in 1982 together with the Swedish biochemists Sune Bergström and Bengt Samuelsson .
  • If that was the culmination point, it was not the end point. The reason for the particular strength of acetylsalicylic acid turned out to be that it acetylated the prostaglandin-forming enzymes, the cyclooxygenases . It differs from all other non-steroidal anti-inflammatory drugs because of the atomic bond between inhibitor and enzyme. Finally, the knowledge from 1990 to 1993 that there are at least two cyclooxygenases triggered further efforts by the pharmaceutical industry, which for the time being did not lead to a “super aspirin” but to the Vioxx scandal .

The priority question

A controversial discussion arose after the Second World War about the priority - primarily in the production of acetylsalicylic acid . Hoffmann's laboratory journals show that it was he who first synthesized acetylsalicylic acid on August 10, 1897. According to tradition, he wanted to give his father, who suffered from arthritis and took salicylic acid, a better tolerated preparation. In 1949, however, Eichengrün, who as a "privileged full Jew" had only been deported to the Theresienstadt concentration camp in 1944 and liberated by the Red Army in 1945, claimed that he had the idea that Hoffmann had only carried it out. Dreser delayed the introduction because he thought the substance was heart-damaging, and he, Eichengrün, pushed through the clinical trial.

The priority question has been examined in detail three times, by Michael de Ridder, the pharmaceutical historian Walter Sneader and the chemical historian Elisabeth Vaupel . De Ridder includes heroin and concludes that “the sources are ambiguous and yet speak more in favor than against that the invention of aspirin and heroin corresponded to a collective scientific achievement” - that the traditional award to Hoffmann alone is therefore unfounded. Sneader writes (from the English): “It is most likely that Arthur Eichengrün was telling the truth when he wrote that acetylsalicylic acid was synthesized under his guidance and was not introduced in 1899 without his intervention.” According to Vaupel, “the synthesis and market introduction was probably not the work of a single man, but the result of teamwork ...: Hoffmann probably owed Eichengrün to the suggestion to modify the pharmaceutical properties of the long-known salicylic acid by acetylation so that a better tolerated drug was created. ... Eichengrün's claim to have been the co-discoverer of aspirin remains credible, but cannot be proven by written sources. "

Individual evidence

  1. ↑ a b c d Hans H. Meyer: Heinrich Dreser † . In: Archives of Experimental Pathology and Pharmacology . 106, 1925, pp. I-VII. doi : 10.1007 / BF01861596 .
  2. ^ A b c E. Lomnitz: Heinrich Dreser † . In: Therapeutic Reports . 1925, pp. 78-81.
  3. ↑ Michael de Ridder , Heroin: from drugs to drugs, p. 38. - Jürgen Lindner, Heinz Lüllmann: Pharmacological institutes and biographies of their directors, p. 145 and p. 175. Editio Cantor, Aulendorf 1996, ISBN 3-87193-172 -1 . - In 1897 Carl Jacobj took over the vacant chair for pharmacology in Göttingen .
  4. ^ H. Dreser: About heart work and heart poisons . In: Archives of Experimental Pathology and Pharmacology . 24, 1888, pp. 221-240. doi : 10.1007 / BF01918403 .
  5. ↑ H. Dreser: Pharmacological investigations on the lobeline of Lobelia inflata . In: Archives of Experimental Pathology and Pharmacology . 26, 1890, pp. 237-266. doi : 10.1007 / BF01829470 .
  6. ^ Leopold Ther : Pharmacological methods. Stuttgart, Wissenschaftliche Verlagsgesellschaft mbH 1949, p. 251
  7. ^ A b Paul Trendelenburg : Basics of the general and special drug prescription. Leipzig, Vogel 1926.
  8. ↑ H. Dreser: About diuresis and its influence by pharmacological means . In: Archives of Experimental Pathology and Pharmacology . 29, 1892, pp. 303-319. doi : 10.1007 / BF01966100 .
  9. ↑ H. Dreser: The dosage of inhalation anesthetics . In: Archives of Experimental Pathology and Pharmacology . 37, 1896, pp. 375-384. doi : 10.1007 / BF01824926 .
  10. ^ Stanislav Kazda and Günter Thomas: Pharmacological Institute, Bayer AG. In: Athineos Philippu: History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries, pp. 776–786. Innsbruck, Berenkamp 2004. ISBN 3-85093-180-3 .
  11. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 358, 1998, pp. 1-109, here pp. 26-27. doi : 10.1007 / PL00005229 .
  12. ↑ H. Dreser: About a hypnotic from the series of urethanes. In: Negotiations of the Society of German Natural Scientists and Doctors. 71st Assembly in Munich. 17.-23. November 1899. Second part. II half. Medicinal departments. Leipzig, Vogel 1900, pp. 46–49.
  13. ↑ H. Dreser: About 1,3-dimethylxanthine and its diuretic effect in healthy people . In: Archives for the entire physiology of humans and animals . 102, 1904, pp. 1-35. doi : 10.1007 / BF01679142 .
  14. ^ H. Dreser: Experiments on theocindiuresis on healthy people . In: Berliner Klinische Wochenschrift . 40, 1903, pp. 953-956.
  15. ↑ O. Minkowski: About Theocin (Theophylline) as Díureticum . In: Therapy of the Present . 43, 1902, pp. 490-493.
  16. ↑ K. Turnheim: Diuretics. In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pages 509-523. ISBN 978-3-437-42522-6 .
  17. ↑ a b Elisabeth Vaupel in Kultur & Technik, p. 46 (2005): Laurel for oak green - homage to a forgotten Jewish chemist. (PDF; 8.3 MB)
  18. ↑ H. Dreser: Pharmacological studies on silver effects . In: Archives internationales de Pharmacodynamie et de Thérapie . 18, 1908, pp. 105-116.
  19. ^ Leopold Ther : Pharmacological methods. Stuttgart, Wissenschaftliche Verlagsgesellschaft mbH 1949, p. 125.
  20. ↑ a b c d e f Michael de Ridder: Heroin. From medicine to drug. Frankfurt and New York, Campus-Verlag 2000 ISBN 3-593-36464-6 . The book is based on the author's dissertation from 1991.
  21. ↑ for example: G. Ciamician, P. Silber: On the knowledge of curcumin . In: Ber. German chem. Ges. 30 , 192 (1897)
  22. ^ European Monitoring Center for Drugs and Drug Addiction: 2011 Annual report on the state of the drugs problem in Europe . Accessed November 28, 2011.
  23. ^ Nicolai Kuhnert: Hundred years of aspirin. In: Chemistry in our time , 1999, 33, pp. 213-220; doi : 10.1002 / ciuz.19990330406 Retrieved November 28, 2011.
  24. ↑ a b c Harry OJ Collier: The story of aspirin. In: MJ Parnham and J. Bruinvels (Eds.): Discoveries in Pharmacology, Volume 2, Haemodynamics, Hormones & Inflammation. Amsterdam, Elsevier 1984, pp. 555-593. ISBN Series 0-444-80492-7.
  25. ↑ a b Arthur Eichengrün: 50 years of aspirin . In: The Pharmacy . 4, 1949, pp. 582-584.
  26. ↑ Erik Verg: Milestones - 125 Years of Bayer 1863–1988 . Leverkusen, Bayer 1988, ISBN 3-921349-48-6 .
  27. ↑ a b c d H. Dreser: On the effect of some derivatives of morphine on respiration . In: Archives for the entire physiology of humans and animals . 72, 1898, pp. 485-521. doi : 10.1007 / BF01671512 .
  28. ↑ a b Floret: Clinical trials on the effect and use of heroin . In: Therapeutic monthly notebooks . 12, 1898, p. 512.
  29. ↑ a b c H. Dreser: Pharmacological information about aspirin (acetylsalicylic acid) . In: Archives for the entire physiology of humans and animals . 76, 1899, pp. 306-318. doi : 10.1007 / BF01662127 .
  30. ^ A b c Kurt Witthauer: Aspirin, a new salicylic preparation . In: Die Heilkunde: Monthly for practical medicine . 3, 1899, pp. 396-398.
  31. ↑ H. Dreser: Pharmacological information about some morphine derivatives . In: Therapeutic monthly notebooks . 12, 1898, pp. 509-512.
  32. ↑ E. Starkenstein: The Papaveraceenalkaloids. In: A. Heffter (Hrsg.): Handbuch der experimental Pharmakologie, second volume, 2nd half. Berlin, published by Julius Springer 1924, pp. 817–1103, here pp. 955–960.
  33. ↑ Erich Harnack: About the toxicity of heroin (diacetylmorphine) . In: Münchener Medicinische Wochenschrift . 46, 1899, pp. 881-884.
  34. ↑ V. Höllt and C. Allgaier: analgesics . In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pages 219–244. ISBN 978-3-437-42522-6 .
  35. ↑ Julius Wohlgemuth: About aspirin (acetylsalicylic acid) . In: Therapeutic monthly notebooks . 13, 1899, pp. 276-278.
  36. ↑ K. Starke: Thomas Mann's remedies . In: German Medical Weekly . 129, 2004, pp. 2770-2776. doi : 10.1055 / s-2004-836110 .
  37. ↑ JR Vane: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs . In: Nature New Biology . 231, 1971, pp. 232-235. doi : 10.1038 / newbio231232a0 .
  38. ↑ Lawrence J. Marnett: The coxib experience: a look in the rearview mirror . In: Annual Review of Pharmacology and Toxicology . 49, 2009, pp. 265-290. doi : 10.1146 / annurev.pharmtox.011008.145638 .
  39. ^ Neighbor Hitler: Führer Cult and Destruction of Home on Obersalzberg by Ulrich Chaussy, p. 59 contains exit certificate on September 20, 1894 on p. 132
  40. ↑ W. Sneader: The discovery of aspirin: a reappraisal. In: BMJ (Clinical research ed.). Volume 321, number 7276, 2000 Dec 23-30, pp. 1591-1594, ISSN  0959-8138 . PMID 11124191 . PMC 1119266 (free full text).
personal data
SURNAME Dreser, Heinrich
BRIEF DESCRIPTION German pharmacologist
DATE OF BIRTH October 1, 1860
PLACE OF BIRTH Darmstadt
DATE OF DEATH December 21, 1924
Place of death Zurich