Pharmakogenetik in der Psychiatrie

Zusammenfassung

Der Erfolg einer Behandlung mit Psychopharmaka wird durch viele Faktoren beeinflusst, darunter auch durch Varianten von Genen, die sowohl pharmakokinetische als auch pharmakodynamische Eigenschaften der Medikamente regulieren. Obwohl die pharmakogenetische Forschung in der Psychiatrie noch in den Anfängen steht, wurde bereits deutlich, dass zumindest einigen Polymorphismen in Genen der Serotonin-Rezeptoren, des Serotonin-Transporters sowie der Dopamin-Rezeptoren eine Rolle bei der Wirkung und Nebenwirkung der Substanzen zukommt. Neuere Untersuchungen beziehen sich auf Strukturen jenseits der initialen Zielproteine der Substanzen, wie die G-Proteine, welche die Kaskade der Signaltransduktion initiieren und damit den Ausgangspunkt für eine Veränderung der Genexpression darstellen. Vor allem die neue Strategie der Pharmakogenomik mit Darstellung von Genexpressions-Profilen hat das Potenzial aufschlussreiche Einblicke in die bis heute nicht geklärten Langzeiteffekte und Wirkmechanismen von Psychopharmaka auf molekularer Ebene zu gewähren.

Summary

Genetic factors are supposed to play a major role for the differences in response to treatment or the incidence of adverse drug effects in psychopharmacotherapy. The aim of pharmacogenetics is to elucidate this variability due to hereditary differences. According to the hypotheses on the mechanisms of drug action, several mutations in genes coding for neurotransmitter-receptors, -degrading enzymes, transport proteins or enzymes of the drug metabolizing system have been identified and investigated. Although there exists some controversy among the results, there is increasing incidence that several polymorphisms within the genes coding for serotonin and dopamine receptors and the serotonin transporter may be involved in drug action. Recent investigation is focusing the structures beyond the initial drug targets, as the G-proteins, which are initiating the signal transduction cascade and are thus the first step for alterations in gene expression. Especially the new research field of pharmacogenomics, which investigates the complex gene and/or protein expression in response to a given drug, may lead to the development of novel and saver drugs.

Schlüsselwörter

Pharmakogenetik - Antidepressiva - Neuroleptika - Polymorphismen

Keywords

Pharmacogenetics - antidepressants - neuroleptics - polymorphism

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