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Transporterhypothese der Pharmakoresistenz von Epilepsien

Transporter hypothesis of pharmacoresistant epilepsy

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Zusammenfassung

An der Blut-Hirn-Schranke können Effluxtransporter den Übertritt von Wirkstoffen in das Gehirn effizient limitieren. Im epileptischen Gehirn kann infolge der Anfallsaktivität die Expression dieser Transportsysteme erhöht sein. Mit der sog. Transporterhypothese pharmakoresistenter Epilepsie wird postuliert, dass die Überexpression der Transporter die Gehirngängigkeit und damit die Wirksamkeit von Antiepileptika einschränken kann. Experimentelle Befunde aus Nagermodellen bestätigen die Hypothese in verschiedener Hinsicht. Durch Anwendung bildgebender Verfahren mit Darstellung der Funktion des Effluxtransporters P-Glykoprotein wird derzeit versucht, zu prüfen, ob sich eine Korrelation zwischen der Transporterfunktion und der Pharmakosensitivität bei Epilepsiepatienten darstellen lässt. Die weiterführende Prüfung der Hypothese ist von besonderem Interesse, da die Prävention der Transporterhochregulation ein interessantes neues therapeutisches Konzept bieten könnte.

Abstract

Efflux transporters at the blood–brain barrier can efficaciously limit the penetration of various compounds into the brain. In the epileptic brain, seizure activity causes an up-regulation of efflux transporters. The transporter hypothesis suggests that this up-regulation can limit brain access to and efficacy of antiepileptic drugs. This hypothesis has been substantiated by experimental findings from rodent models. Based on imaging analysis aiming to determine the function of the efflux transporter P-glycoprotein, it is currently being tested whether a correlation exists between transporter function and pharmacosensitivity in patients with epilepsy. Further validation of the hypothesis is of particular interest as the prevention of transporter up-regulation might offer an interesting novel therapeutic concept.

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Abb. 1

Notes

  1. ABCC: C-Subfamilie der „ATP-binding-cassette“-Transporter.

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  1. Institut für Pharmakologie, Toxikologie, und Pharmazie, Ludwig-Maximilians-Universität München, Koeniginstr. 16, 80539, Munich, Deutschland

    H. Potschka

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Potschka, H. Transporterhypothese der Pharmakoresistenz von Epilepsien. Z. Epileptol. 23, 152–160 (2010). https://doi.org/10.1007/s10309-010-0105-2

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