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Vigabatrin — experimentelle und klinische Pharmakologie

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Vigabatrin

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Zusammenfassung

γ-Aminobuttersäure (GABA) ist der hauptsächliche inhibitorische Transmitter im Zentralnervensystem, das normalerweise einer ständigen Inhibition durch diesen Transmitter unterliegt. Bei epileptischen Patienten sind im Liquor cerebrospinalis teilweise erniedrigte GABA-Konzentrationen nachgewiesen worden (Wood et al. 1979; Manyam et al. 1980; Löscher et al. 1981) und als Ausdruck einer Disinhibition angesehen worden. Umgekehrt hat man durch eine Erhöhung der zentralen GABA-Konzentration einen Anstieg der Schwelle für Elektro- und Pentetrazolkrämpfe nachweisen können (Frey 1976). Eine kausale Rolle der GABA für die Pathogenese epileptischer Erkrankungen lag demnach nahe und führte zu dem Versuch, durch Hemmstoffe des GABA-Abbaus zu neuen therapeutischen Möglichkeiten in der Epilepsiebehandlung zu kommen. Hierzu boten sich Hemmstoffe der GABA-Transaminase (GABA-T) an. Der bis dahin bekannte Vertreter der GABA-T-Hemmstoffe, Aminooxyessigsäure, schien dazu wegen erheblicher Toxizität wenig geeignet (Löscher u. Frey 1978), aber es gelang der Arbeitsgruppe von Schechter in Frankreich, unter anderen Stoffen Vigabatrin zu entwickeln und im Tierversuch antikonvulsive Wirkungen dieser Verbindung zu zeigen (Jung et al. 1977; Lippert et al. 1977; Schechter et al. 1977) (Abb. 1).

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  1. H.-H. Frey
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Editors and Affiliations

  1. Schweizerische Epilepsie-Klinik, Bleulerstraße 60, CH-8008, Zürich, Switzerland

    Günter Krämer

  2. Arbeitsgruppe Epilepsieforschung, Goethestraße 5, D-14163, Berlin, Germany

    Dieter Schmidt

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Frey, HH. (1994). Vigabatrin — experimentelle und klinische Pharmakologie. In: Krämer, G., Schmidt, D. (eds) Vigabatrin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77131-6_2

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