Die Bedeutung des glutamatergen Systems für Pathophysiologie und Pharmakotherapie der Depression: präklinische und klinische Daten

Zusammenfassung

Dem glutamatergen System wird eine zunehmende Rolle in der Pathophysiologie affektiver Störungen zugeschrieben. Der Neurotransmitter Glutamat ist der wichtigste exzitatorische Transmitter im zentralen Nervensystem. An der Regulation des glutamatergen Systems sind Gliazellen maßgeblich beteiligt. In verschiedenen Untersuchungen wurde eine Dysfunktion bzw. reduzierte Anzahl von Gliazellen bei Patienten mit depressiver Störung beschrieben. Daraus könnte sich bei der Depression eine Überfunktion des glutamatergen Systems mit einer toxisch wirkenden Akkumulation von Glutamat entwickeln. Gängige Antidepressiva greifen in den Glutamat-Metabolismus ein und antiglutamaterge Substanzen (z. B. Riluzol) und NMDA-Rezeptor-Antagonisten (z. B. Ketamin) zeigten antidepressive Wirksamkeit in hauptsächlich präklinischen und einigen klinischen Studien. Weitere Substanzen sind in Prüfung. Diese Übersicht liefert Einblicke über die neuesten Entwicklungen auf diesem Gebiet.

Abstract

An increasing significance has been attributed to the glutamatergic system in the pathophysiology of affective disorders. Glutamate is the most important excitatory neurotransmitter in the central nervous system. Glia cells are crucial regulators of the glutamatergic metabolism. Several studies have reported a dysfunction or reduced number of glia cells in patients suffering from depression. This could result in hyperfunctioning of the glutamatergic system leading to a toxic accumulation of glutamate. Commonly used antidepressants influence the glutamate metabolism and antiglutamatergic substances [e. g., riluzol] and NMDA-receptor antagonists [e. g., ketamine] have shown antidepressant properties in mostly preclinical and some clinical trials. Further substances are currently being investigated. This review provides an insight into the newest developments in this field.

Schlüsselwörter

Glutamat - Depression - NMDA Rezeptor - Ketamin - Gliazelle

Keywords

glutamate - depression - NMDA receptor - ketamine - glia cells

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