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Der Nuklearmediziner 2002; 25(3): 202-207
DOI: 10.1055/s-2002-34107
Dopaminerges System

© Georg Thieme Verlag Stuttgart · New York

Nuklearmedizinische Rezeptordiagnostik bei schizophrenen Patienten unter Therapie mit typischen und atypischen Neuroleptika

Receptor Imaging of Schizophrenic Patients under Treatment with Typical and Atypical NeurolepticsS. Dresel1 , E. Meisenzahl2 , J. Scherer3 , K. Tatsch1
  • 1Klinik und Poliklinik für Nuklearmedizin der Ludwig-Maximilians-Universität München
  • 2Psychiatrische Klinik der Ludwig-Maximilians-Universität München
  • 3Bezirkskrankenhaus Haar
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Publication History

Publication Date:
16 September 2002 (online)

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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

Ziemssenstr. 1

80336 München

Phone: +49/89/51 60-24 32

Fax: +49/89/51 60-44 88

Email: dresel@nuk.med.uni-muenchen.de