Über die Lokalisation des Veronals, der Phenyläthyl- und Diallylbarbitursäure im Gehirn

Keeser, E.; Keeser, J.

doi:10.1007/bf01862960

Cited by 35 publications

(3 citation statements)

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“…It is probable that it prevents emesis by depressing the vomiting center and probably other higher centers connected with the vomiting act. Barbiturates such as pentobarbital depress the cerebral cortex, and also the hypothalamic portion of the diencephalon and the subcortical ganglia, while the bulbo-spinal reflexes are very little affected (22,23). The failure to affect emesis indicates that possibly the above mentioned areas are not a necessary portion of the vomiting reflex.…”

Section: Discussionmentioning

confidence: 99%

Studies on the Mechanism of Vomiting Produced by Staphylococcus Enterotoxin

Bayliss

1940

Journal of Experimental Medicine

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Among the toxins produced by certain strains of staphylococci is one which is capable of causing food poisoning symptoms in man. Although a number of workers including Denyes (1), Owen (2), and Barber (3) had called attention to the etiological r61e of staphylococci in certain outbreaks of acute illness characterized by nausea, vomiting, and diarrhea, it was not until the work of Dack (4) and Jordan (5) and their coworkers that interest was stimulated in staphylococcus food poisoning. These later investigators demonstrated that the symptoms were due to a filterable toxin which was thermostable. This toxin was found to be quite distinct from the hemolytic, lethal, and dermo-necrotic toxins which are relatively thermolabile. Since its main effect seemed to be on the gastro-intestinal tract, it was termed enterotoxin.The clinical symptoms in man usually begin 2 to 4 hours after ingestion of the contaminated food, and include dizziness, nausea, vomiting, diarrhea, and weakness. Recovery is rapid, and the individual feels practically well 24 hours later. Fatalities are rare, and are probably caused by an actual tissue invasion by the staphylococcus rather than by the enterotoxin alone. In the fatal case reported by Blackman (6), the illness began with the above symptoms, but at necropsy a staphylococcal infection of the jejunum and ileum was found.The investigation of enterotoxin-producing organisms has been retarded by the fact that, until recently, the only known susceptible subjects were man and the monkey, and these exhibited considerable variation in the response to enterotoxin. In 1936, Dolman, Wilson, and Cockcroft (7) demonstrated that kittens injected intraperitoneally with formalinized or

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Section: Discussionmentioning

confidence: 99%

Studies on the Mechanism of Vomiting Produced by Staphylococcus Enterotoxin

Bayliss

1940

Journal of Experimental Medicine

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“…It was soon recognized that the brain is the chief site of action of barbiturates. Based on early studies indicating a specific distribution of barbiturates in the brain, it was proposed that the anesthetic effect is mediated via the brain stem, whereas the sedative/hypnotic effect is mediated via a “sleep center” in the thalamus (Keeser & Keeser, 1927). However, subsequent studies showed ubiquitous distribution of barbiturates in the brain (Koppanyi & Dille, 1935).…”

Section: Early Studiesmentioning

confidence: 99%

How theories evolved concerning the mechanism of action of barbiturates

2012

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Summary The barbiturate phenobarbital has been in use in the treatment of epilepsy for 100 years. It has long been recognized that barbiturates act by prolonging and potentiating the action of γ‐aminobutyric acid (GABA) on GABAA receptors and at higher concentrations directly activating the receptors. A large body of data supports the concept that GABAA receptors are the primary central nervous system target for barbiturates, including the finding that transgenic mice with a point mutation in the β3 GABAA‐receptor subunit exhibit diminished sensitivity to the sedative and immobilizing actions of the anesthetic barbiturate pentobarbital. Although phenobarbital is only modestly less potent as a GABAA‐receptor modulator than pentobarbital, phenobarbital is minimally sedating at effective anticonvulsant doses. Possible explanations for the reduced sedative effect of phenobarbital include more regionally restricted action; partial agonist activity; reduced propensity to directly activate GABAA receptors (possibly including extrasynaptic receptors containing δ subunits); and reduced activity at other ion channel targets, including voltage‐gated calcium channels. In recent years, substantial progress has been made in defining the structural features of GABAA receptors responsible for gating and allosteric modulation by drugs. Although the precise sites of action of barbiturates have not yet been defined, the second and third transmembrane domains of the β subunit appear to be critical; binding may involve a pocket formed by β‐subunit methionine 286 as well as α‐subunit methionine 236. In addition to effects on GABAA receptors, barbiturates block AMPA/kainate receptors, and they inhibit glutamate release through an effect on P/Q‐type high‐voltage activated calcium channels. The combination of these various actions likely accounts for their diverse clinical activities. Despite the remarkable progress of the last century, there is still much to learn about the actions of barbiturates that can be applied to the discovery of new, more therapeutically useful agents.

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“…Die wesentliche Wirkung des Dauerschlafs sollte einerseits in einer der Allgemeinanästhesie ähnlichen Ausschaltung "zentraler Reize" durch die Sedativa bestehen, andererseits in der Erzeugung von anhaltender "körperlicher Hilfsbedürftigkeit", die nach Klaesi bei schwerkranken Patienten überhaupt erst den Aufbau eines psychotherapeutisch nutzbaren "Rapports" ermöglichte. Für die Methode Klaesis sprachen auch pharmakologische Studien, die nach damaligem Verständnis eine Kumulation von Barbituraten in für den Schlaf relevanten Hirnstrukturen nachwiesen [25]. Hierbei fällt vor allem auf, dass Müller-Hegemannim Unterschied zu Klaesiin seiner Rezeptur keine "modernen" Barbitursäurederivate anwandte, sondern auf Sedativa zurückgriff, die seit der zweiten Hälfte des 19.…”

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Vermischung von Politik und Wissenschaft in der DDR. Die Untersuchung der Todesfälle an der Leipziger Neurologisch-Psychiatrischen Universitätsklinik unter Müller-Hegemann 1963

Steinberg

Weber

2011

Fortschr Neurol Psychiatr

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This study presents archival sources that shed light on a topic still being discussed by psychiatrists in East Germany: the death of two patients at the Leipzig Department that occurred in 1960 and 1962 under the directorship of Dietfried Müller-Hegemann. These fatalities were supposed to have been induced by obsolete psychotropic drugs and were associated with Ivan Pavlov's hypnotherapy. The incidents were investigated both by highest administrative bodies and the General State Prosecutor of the former GDR. Archival sources suggest that lower party organs and the ministerial administration tried to make use of the proceedings to bring about the downfall of the head of the Leipzig Department, who had become ideologically suspicious. However, the official General State Prosecutor's investigation ascertained that both Müller-Hegemann and Christa Kohler, head of the psychotherapeutic ward, were not to be held responsible. Although the SED Central Committee at first tried to influence the outcome on the basis of ideological reservations made by the university party organisation, it finally accepted and confirmed the judgment of the General State Prosecutor. Hence, in this case, the highest party bodies followed arguments that were the result of an independent investigation and were not influenced by an individual bias or ideological motives.

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Über die Lokalisation des Veronals, der Phenyläthyl- und Diallylbarbitursäure im Gehirn

Cited by 35 publications

References 1 publication

Studies on the Mechanism of Vomiting Produced by Staphylococcus Enterotoxin

Studies on the Mechanism of Vomiting Produced by Staphylococcus Enterotoxin

How theories evolved concerning the mechanism of action of barbiturates

Vermischung von Politik und Wissenschaft in der DDR. Die Untersuchung der Todesfälle an der Leipziger Neurologisch-Psychiatrischen Universitätsklinik unter Müller-Hegemann 1963

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