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Pharmakologie und Pharmakokinetik von Nikotin

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Tabakabhängigkeit

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Abstract

•Nikotin ist eines der am stärksten toxisch wirkenden Alkaloide mit einer Sucht erzeugenden Wirkung, die mit der von Kokain und Heroin zu vergleichen ist. Bei fortgesetzter Zufuhr in Form des Tabakrauchens (insbesondere von Zigaretten) kann es zur Abhängigkeit führen.

•Seine Wirkungen entfaltet Nikotin über die Freisetzung von Botenstoffen im ZNS, von denen Dopamin, Noradrenalin und 5-Hydroxytryptamin eine besondere Rolle spielen.

•Nikotin wirkt über die Stimulation von nikotinergen Acetylcholinrezeptoren (nAChR). Hierbei handelt es sich um Ionentransporter, die im zentralen und peripheren Nervensystem vorkommen und mit verschiedenen Transmittersystemen verknüpft sind. Die Struktur der nAChR ist weitgehend aufgeklärt und die verschiedenen Subeinheiten (α4β2, α3β4, α7 etc.) können verschiedenen nervalen Strukturen zugeordnet werden. Die Angriffspunkte von Agonisten und kompetitiven bzw. nichtkompetitiven Antagonisten lassen sich im Rezeptorsystem lokalisieren.

•Pharmakokinetische Untersuchungen mit Nikotinpräparaten berücksichtigen zumeist die Plasmaspiegel in ihrem zeitlichen Verlauf, während in klinischen Studien auch die Cotininplasmaspiegel wichtige Aussagen liefern.

•Im Gegensatz zur Aufnahme von Zigarettennikotin wird das aus galenischen Präparaten verfügbare Nikotin abhängig von der Zubereitungsform sehr viel langsamer und zu einem geringeren Anteil freigesetzt, was letztlich auch der Grund dafür ist, dass diese Präparate keine Abhängigkeit erzeugen.

•Neben äußeren Faktoren ist die Ausbildung der Nikotinabhängigkeit auch auf genetische Faktoren zurückzuführen. Dabei spielt das Zytochrom-P450-Subenzym 2A6, die Verteilung von Dopaminrezeptoren (DRD1 und DRD2) und deren Allelen (A1 und A2), aber auch das Dopamintransportergen SLC6A3 eine Rolle für den Start einer Raucherkarriere und die Nikotinabhängigkeit.

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    Knut-Olaf Haustein

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(2008). Pharmakologie und Pharmakokinetik von Nikotin. In: Haustein, KO. (eds) Tabakabhängigkeit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73309-6_4

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