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Nervenheilkunde 2007; 26(11): 993-998
DOI: 10.1055/s-0038-1626952
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Mechanismen der Pharmakoresistenz

Mechanisms of pharmacoresistance
H. Potschka
1   Institut für Pharmakologie, Toxikologie und Pharmazie, Ludwig-Maximilians-Universität München (Leiter: Prof. Dr. H. Potschka)
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Publication History

Publication Date:
19 January 2018 (online)

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Zusammenfassung

Trotz der Einführung neuer Antiepileptika erweisen sich weiterhin etwa ein Drittel der Epilepsiepatienten als pharmakoresistent. Die Pharmakoresistenz kann dabei von Beginn der Erkrankung an ausgeprägt sein oder sich im weiteren Verlauf entwickeln. Von der Aufklärung der zu Grunde liegenden Mechanismen verspricht man sich Erkenntnisse, die in der Entwicklung neuer Antiepileptika genutzt werden können und eine Basis für die Entwicklung von neuen therapeutischen Strategien zur Überwindung der Pharmakoresistenz bilden. Untersuchungen der vergangenen Jahre haben Hinweise dafür erbracht, dass Arzneimitteltransportsysteme an der Blut-Hirn-Schranke bei pharmakoresistenten Patienten erhöhte Expressionsraten aufweisen und durch einen Auswärtstransport von Antiepileptika deren Wirksamkeit einschränken können. Zudem konnten epilepsieassoziierte Veränderungen an verschiedenen Zielstrukturen von Antiepileptika nachgewiesen werden, die den Effekt der Antiepileptika limitieren. Zukünftige Untersuchungen müssen zeigen, ob die neuen Erkenntnisse für eine Optimierung der therapeutischen Situation genutzt werden können.

Summary

Despite the launch of a series of new antiepileptic drugs, epilepsy in about one third of the patient population is considered to be pharmacoresistant. Thereby, pharmacoresistance can exist with onset of the disease, but can also develop with progression of epilepsy. The analysis of the underlying mechanisms promises findings that can be used for the development of new antiepileptic drugs, and can be used for the development of new therapeutic strategies to overcome pharmacoresistance. Research during the last years indicates that multidrug transporters at the bloodbrain barrier are overexpressed in pharmacoresistant patients and can mediate efflux of antiepileptic drugs, thereby restricting their efficacy. Furthermore epilepsy-associated changes have been detected in antiepileptic drug target structures, which can limit the drug effect. Future investigations have to clarify, whether the findings can be used for the optimization of the therapeutic situation.

Schlüsselwörter

Antiepileptika - Pharmakoresistenz - Epilepsie

Keywords

Antiepileptic drugs - pharmacoresistance - epilepsy
 

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