Der Schmerz

, Volume 21, Issue 4, pp 318–330 | Cite as

Von der Weidenrinde zu den Coxiben

Entwicklung der antiphlogistischen Analgetika
Schwerpunkt: Geschichte der Schmerztherapie

Zusammenfassung

Antiphlogistische Analgetika sind die weltweit am meisten gebrauchten Arzneistoffe. Sie haben sich in den vergangenen 130 Jahren aus den Salicylaten, den Inhaltsstoffen zahlreicher Pflanzen, aus dem auf der Suche nach einem Ersatzstoff für das Chinidin in Erlangen synthetisierten Phenazons und aus dem zufällig in Straßburg entdeckten Acetanylid (Vorläufer des Paracetamols) entwickelt. Die systematische Suche nach pharmakologischen Verwandten sowie chemischen Varianten in Tiermodellen führte zur Entdeckung einer Reihe auch heute noch gebrauchter antiphlogistischer Analgetika, die wir kollektiv als NSAID (nonsteroidal antiinflammatory drugs) oder NSAR (nichtsteroidale Antirheumatika) bezeichnen. Ihnen allen ist gemein, dass sie entzündliche Schmerzen lindern, aber in unterschiedlichem Umfang die Blutgerinnung behindern, Asthmareaktionen auslösen, den Blutdruck erhöhen, zu Magen-Darm-Ulzerationen führen und die Nierenfunktion stören. Die moderne, molekularbiologische Forschung hat die Ursachen für beides, Wirkungen und unerwünschte Effekte, aufgeklärt: Die Hemmung der Zyklooxygenasen. Eine erste Konsequenz daraus war die Entwicklung der so genannten selektiven Zyklooxygenase-2-Hemmer: Sie bedingen bei gleicher Wirksamkeit wie die traditionellen NSAID weniger gastrointestinale Störwirkungen, sie führen nicht zu asthmatischen Reaktionen und behindern die Blutgerinnung nicht. Ob sie auf der anderen Seite häufiger zu kardiovaskulären Problemen beitragen, ist zurzeit umstritten. Die Aufklärung des Wirkungsmechanismus führte allerdings auch zu Hinweisen auf neue Gruppen analgetischer Wirkstoffe, die nun ihrerseits die Kontrolle nozizeptiver Informationen im Rückenmark auf der Basis des inhibitorischen Transmitters Glycin aktivieren können. Erste Substanzen dieser neuer Klassen sind in den kommenden Jahren zu erwarten.

Schlüsselwörter

Analgetika NSAID Zyklooxygenasehemmer Geschichte 

From willow bark to the coxibs

Development of antiphlogistic analgesics

Abstract

Antiphlogistic analgesics comprise the most widely used class of drugs worldwide. These compounds derive more or less directly from three prototypes which were discovered about 130 years ago in Central Europe: acetylsalicylic acid (aspirin), acetanilide (the forerunner of acetaminophen), and phenazone. All of them are still available. Attempts to improve their effect/side effect spectrum and enhance their analgesic activity led to the development of animal models of inflammatory pain which allowed for the screening and discovery of the so-called aspirin-like drugs, also termed nonsteroidal antiinflammatory drugs (NSAIDs) or cyclooxygenase inhibitors. This group presently dominates the market despite the fact that all these compounds imply the risk of unwanted drug effects, including gastrointestinal ulcers, renal dysfunction, inhibition of blood coagulation, pseudoallergic reactions, and possibly also accelerated development of atherosclerosis. Attempts to reduce these unwanted drug effects on the basis of molecular pharmacological insights resulted in the development of the so-called selective cyclooxygenase-2 inhibitors which are presently discussed ambiguously. These compounds appear to go along with less gastrointestinal toxicity, they do not inhibit blood coagulation, and have a reduced propensity for causing pseudoallergic asthmatic attacks. They may, on the other hand, cause more unwanted cardiovascular effects than the traditional NSAIDs. Hope for further reduction of unwanted drug effects comes from the recently discovered role of glycinergic spinal pain control. It is hoped that new classes of analgesic compounds may result from these new glycinergic mechanisms.

Keywords

Analgesics NSAIDs Cyclooxygenase inhibitors History 

Notes

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

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Copyright information

© Springer Medizin Verlag 2007

Authors and Affiliations

  1. 1.Institut für Experimentelle und Klinische Pharmakologie und ToxikologieFriedrich-Alexander-Universität Erlangen-NürnbergErlangenDeutschland

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