Interaction of progesterone derivatives with the digitalis target enzyme: Impact of glycosidation on inhibitory potency

Weiland, Jürgen; Schönfeld, Werner; Menke, Karl-Heinz; Repke, K.

doi:10.1016/s1043-6618(05)80102-1

Cited by 8 publications

References 26 publications

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Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

et al. 1995

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Der Arzt William Withering führte 1785 mit seinem Buch „An Account of the Foxglove and some of its Medical Uses”︁ Präparate aus Digitalisblättern in die Therapie der Wassersucht (des Herzversagens) ein und erklärte: „The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.”︁ Diese Bemerkungen sind hier vom Seniorautor angeführt, da er die Schwierigkeit sieht, einen ausgewogenen Bericht über sein lebenslanges Forschungsprojekt zur Digitalis‐Weiterentwicklung zu bieten. Seine Entscheidung, sich der Digitalisforschung zu widmen, entstand am Krankenbett, an dem er als Arzt die furchtbaren Endstadien des Herzversagens erlebte, in denen für die Kranken keine wirkliche Hilfe mehr möglich ist. Unglücklicherweise paßte dieses Vorhaben nicht in das vom Wissenschaftsministerium der DDR dekretierte Forschungsprogramm, so daß er das Digitalisprojekt zugunsten von Biomembran‐Untersuchungen einstellen sollte. Glücklicherweise entging er dem Verdikt durch Etikettierung der digitalisartig wirkenden Steroide als chemische Sonden für die Zellmembran‐lokalisierte Na+/K+ ‐transportierende ATPase, die er gerade als den Digitalisrezeptor erkannt hatte. Über die Arbeit der Autoren wird hier erstmals im Zusammenhang berichtet. Ziel des Überblicks ist, die Forschung für die Lösung einer großen Aufgabe zu fördern: die Entwicklung von Steroidwirkstoffen zur Verhinderung und Heilung der Herzinsuffizienz.

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Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

et al. 1995

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Digitalis Research in Berlin–Buch—Retrospective and Perspective Views

Repke¹,

Megges²,

Weiland³

et al. 1995

Angew. Chem. Int. Ed. Engl.

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“The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.” These declarations, which stem from the famous book “An Account of the Foxglove and some of its Medical Uses” by physician William Withering in 1785 in which he introduced preparations from digitalis leaves in the therapy of dropsy (cardiac failure), are cited here by the senior author because of his awareness of the difficulties in presenting a balanced report on his life‐long research project on the further development of digitalis. His decision to devote himself to digitalis research originated at the bedside, when as a physician he experienced the grim final stages of cardiac failure in which no real help for the patients is possible. Unfortunately, his research project did not fit into the research program decreed by the Ministry of Science of the German Democratic Republic, so that he was ordered to stop the digitalis project in favor of biomembrane studies. Fortunately, he got round the ban simply by labeling the digitalis‐like acting steroids as probes for the cell membrane‐located Na+/K+‐transporting ATPase which he had just recognized as the digitalis target (receptor) enzyme. These and other ventures by the authors are collated here for the first time. The aim of this review is to foster straightforward research for solving a major challenge: the development of steroidal drugs for the prevention and cure of cardiac failure.

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