Zusammenfassung
Die pharmakologische Therapie von Erkrankungen aus dem schizophrenen Formenkreis erfolgt
durch typische und atypische Neuroleptika. Beide Gruppen unterscheiden sich klinisch
im Wesentlichen durch die Eigenschaft, extrapyramidal-motorische Nebenwirkungen hervorzurufen.
Die Besetzung postsynaptischer Dopamin-D2-Rezeptoren wird als ein wesentlicher Aspekt
der antipsychotischen Wirksamkeit der Neuroleptika angesehen. Diese können nuklearmedizinisch
durch [I-123]IBZM-SPECT dargestellt werden. Für das typische Neuroleptikum Haloperidol
wurde eine dosisabhängige, exponentielle Besetzung der Dopamin-D2-Rezeptoren nachgewiesen.
Ab einem Schwellenwert des spezifischen Bindungsindex von 0,4 (Norm: > 0,95) zeigten
mit einer Ausnahme alle untersuchten Patienten extrapyramidal-motorische Nebenwirkungen.
Auch unter Therapie mit dem atypischen Neuroleptikum Clozapin ergab sich eine exponentielle
Dosis-Wirkungsbeziehung mit jedoch einem deutlich flacheren Kurvenverlauf im Vergleich
zu Haloperidol. Extrapyramidal-motorische Nebenwirkungen traten bei diesen Patienten
nicht auf. Neuere, als atypisch eingestufte Neuroleptika wie Risperidon und Olanzapin
zeigten ebenfalls eine exponenzielle Dosis-Wirkungsbeziehung, wobei deren Kurvenverläufe
zwischen denen von Haloperidol und Clozapin lagen. Extrapyramidal-motorische Nebenwirkungen
traten bei den letzteren Neuroleptika seltener als bei Haloperidol, bei Olanzapin
nur bei einem Patienten in unserem eigenen Patientengut auf. Das pharmakologische
Profil atypischer Neuroleptika zeichnet sich neben der Bindung an die postsynaptischen
Dopamin-D2-Rezeptoren auch durch Bindung an Rezeptoren diverser anderer Neurotransmittersysteme,
insbesondere des serotonergen Systems, aus. Somit ist wahrscheinlich, dass die niedrigere
Inzidenz für extrapyramidal-motorische Nebenwirkungen bei atypischen Neuroleptika
durch eine komplexe Interaktion an verschiedenen Neurotransmittersystemen bedingt
ist.
Abstract
Schizophrenic psychosis is typically treated by typical and atypical neuroleptics.
Both groups of drugs differ with regard to induction of extrapyramidal side effects.
The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential
aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed
by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed
an exponential dose response relationship measured by IBZM. Extrapyramidal side effects
were presented by all patients below a threshold of the specific binding of IBZM below
0.4 (with one exception, norm value: > 0.95). Also under treatment with the atypical
neuroleptic clozapine an exponential dose response relationship was found. However,
none of these patients showed extrapyramidal side effects. Recently introduced, new
atypical neuroleptics such as risperidone and olanzapine again presented with an exponential
relationship between daily dose and IBZM binding. The curves of the latter were in
between the curves of haloperidol and clozapine. Extrapyramidal side effects were
documented in a less number of patients treated with risperidone as compared to haloperidol,
for olanzapine only one patient revealed these findings in our own patient group.
The pharmacological profile of atypical neuroleptics shows - in addition to their
binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter
systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal
side effects seen by atypical in comparison to typical neuroleptics is at least in
part most likely due to a complex interaction on a variety of neurotransmitter systems.
Schlüsselwörter
Dopaminrezeptoren - Dopamintransporter - Neuroleptika - Schizophrenie
Key words
Dopamine receptors - Dopamine transporter - Neuroleptics - Schizophrenia
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Priv.-Doz. Dr. med. Stefan Dresel
Klinik und Poliklinik für Nuklearmedizin
Ludwig-Maximilians-Universität München
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eMail: dresel@nuk.med.uni-muenchen.de