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Die Bedeutung von GABAA-Rezeptoren für Pathophysiologie und Therapie der Panikstörung

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Zusammenfassung

Gamma-Aminobuttersäure (GABA) ist der wichtigste inhibitorische Neurotransmitter im Zentralnervensystem. Eine Dysfunktion von GABAA-Rezeptoren spielt eine wichtige Rolle in der Pathophysiologie der Panikstörung. Allgemein bekannt ist die klinische Wirksamkeit von Benzodiazepinen in der Therapie der Panikstörung, Nebenwirkungen limitieren allerdings den Einsatz als Langzeittherapie. Antidepressiva, insbesondere selektive Serotoninwiederaufnahmehemmer, stellen Mittel der ersten Wahl in der Pharmakotherapie der Panikstörung dar. Neuere Untersuchungen konnten zeigen, dass die Erhöhung endogener GABA durch Blockade der GABA-Transaminase mit Vigabatrin oder durch Inhibition von GABA-Transportern mit Tiagabin ebenfalls anxiolytische Eigenschaften entfaltet. Diese neue Interventionsstrategie an der GABA-Bindungsstelle des GABAA-/Benzodiazepin-Rezeptor-Komplexes sowie Agonisten für die Benzodiazepinbindungsstelle mit Selektivität für bestimmte Untereinheiten des Rezeptors stellen interessante neuartige Perspektiven für die Weiterentwicklung der Pharmakotherapie der Panikstörung dar.

Summary

Gamma aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system. Its action is exerted in the brain through GABAA receptors which belong to the family of ligand-gated ion channels. These GABAA receptors consist of various subunits and are targets for benzodiazepines, barbiturates, neuroactive steroids, and distinct anticonvulsive agents. Meanwhile, there is considerable evidence that a dysfunction of GABAA receptors plays an important role in the pathophysiology of panic disorder. The anxiolytic effects of benzodiazepines are widely used in the treatment of panic disorder. Nevertheless, side effects of benzodiazepines, e.g., dependency and withdrawal symptoms, limit their use as a long-term treatment. In the meantime, antidepressants, especially selective serotonin reuptake inhibitors, comprise first-line treatment in the pharmacotherapy of panic disorder. They interfere with the synthesis of endogenous neuroactive steroids that allosterically modulate GABAA receptor function. With regard to experimentally evoked panic attacks in patients with panic disorder and healthy controls, recent investigations demonstrated that enhancing endogenous GABA through the blockade of the GABA transaminase by vigabatrin or inhibition of GABA transporters by tiagabine may exert anxiolytic effects. This novel strategy targeting the GABA binding site of the GABAA/benzodiazepine receptor complex and specific agonists for the benzodiazepine binding site present interesting perspectives for the future pharmacotherapy of panic disorder.

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Authors and Affiliations

  1. Klinik für Psychiatrie und Psychotherapie der Ludwig-Maximilians-Universität München

    R. Rupprecht & P. Zwanzger

  2. Klinik für Psychiatrie und Psychotherapie, Nußbaumstraße 7, 80336 München

    R. Rupprecht

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  1. R. Rupprecht
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  2. P. Zwanzger
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Correspondence to R. Rupprecht.

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Rupprecht, R., Zwanzger, P. Die Bedeutung von GABAA-Rezeptoren für Pathophysiologie und Therapie der Panikstörung. Nervenarzt 74, 543–551 (2003). https://doi.org/10.1007/s00115-002-1433-x

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