Haben die unterschiedlichen Antidepressiva unterschiedliche Wirkmechanismen?

Zusammenfassung

Unsere Kenntnisse über pathophysiologische Mechanismen der Depression oder die Wirkmechanismen der Antidepressiva haben sich in den letzten Jahren erheblich erweitert. Dabei wurde deutlich, dass die Erhöhung der Konzentrationen der Neurotransmitter im synaptischen Spalt oder die Interaktionen mit den entsprechenden Rezeptoren vor allem als initialer Schritt zu betrachten sind, durch den es über zahlreiche Aktivierungsschritte in der Synapse letztendlich zu substantiellen Veränderungen der Proteinexpression und damit der neuronalen Funktion kommt. Auch wenn wir heute zunehmend davon ausgehen, dass diese langfristigen Veränderungen der neuronalen Funktion als sogenannte gemeinsame Endstrecke der Antidepressiva- Wirkung angesehen werden kann, ist der Einfluss der unterschiedlichen initialen Wirkmechanismen sowie deren Interaktion mit den verschiedenen Kompartimenten der Signaltransduktion nicht zu vernachlässigen. Besonders die pharmakogenetischen Studien haben gezeigt, dass die Schnelligkeit des Ansprechens auf die Behandlung doch im erheblichem Maße von diesen Mechanismen beeinflusst wird.

Summary

Our recent knowledge about the pathophysiological basis of major depression and the mechanisms of antidepressant action has increased during the last years. Thus there has been some shift in emphasis from the changes in neurotransmitter concentrations or the interactions of these drugs with the respective receptors towards long lasting adaptive processes within the neurones. According to the present hypotheses, the increase in monoaminergic neurotransmitters can be taken as initial triggering effect, inducing activation of transcription factors and target genes that regulate processes such as neuroprotection and cell survival. Although these long-term adaptive alterations might be the common final pathway of different antidepressant regimens, the different biochemical mechanisms of the different classes of antidepressants together with functionally relevant polymorphisms in genes might be relevant for the latency until onset of therapeutic action.

Schlüsselwörter

Antidepressiva - Signaltransduktion - Neuroplastizität - Pharmakogenetik

Keywords

Antidepressants - signal transduction - neuroplasticity - pharmacogenetics

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