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Fortschr Neurol Psychiatr 2003; 71(8): 415-420
DOI: 10.1055/s-2003-41194
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Die nächste Generation „atypischer” Antipsychotika: Der Beitrag der Positronenemissionstomographie

The Next Generation of „Atypical” Antipsychotics: The Role of Positron Emission TomographyG.  Gründer1, 2 , D.  F.  Wong2
  • 1Psychiatrische Klinik und Poliklinik, Universität Mainz, Deutschland
  • 2Department of Radiology, Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, USA
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Publication History

Publication Date:
11 August 2003 (online)

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Zusammenfassung

Nahezu 15 Jahre Forschung mit der Positronenemissionstomographie (PET) und der Single-Photon-Emissions-Computer-Tomographie (SPECT) haben zu einem weitgehenden Verständnis der Beziehungen zwischen Dosierungen und Plasmakonzentrationen von Antipsychotika einerseits und der Besetzung von (striatalen) D2-artigen Dopaminrezeptoren andererseits sowie der damit assoziierten klinischen Wirkungen und Nebenwirkungen geführt. Mit der Entwicklung der „atypischen” Antipsychotika haben PET-Studien zudem in den letzten Jahren dazu beigetragen, Hypothesen zu der Frage zu entwickeln, auf welchen pharmakologischen Eigenschaften die „Atypie” dieser heterogenen Substanzgruppe beruht. Zu den möglichen Wirkmechanismen zählen der kombinierte D2-/5-HT2-Antagonismus, die präferenziell mesolimbische Bindung des Antipsychotikums sowie dessen rasche Abdissoziation vom D2-Rezeptor. Eine von uns kürzlich vorgestellte PET-Studie zur In-vivo-Charakterisierung des partiellen Dopaminrezeptor-Agonisten Aripiprazol weist nun auf ein weiteres Wirkprinzip hin, das einem Antipsychotikum klinisch „atypische” Eigenschaften verleiht. Aripiprazol, dessen antipsychotische Wirksamkeit in mehreren multizentrischen klinischen Studien belegt ist, führt bei klinisch gebräuchlichen Dosierungen zu einer nahezu vollständigen Sättigung striataler D2-artiger Dopaminrezeptoren; die Inzidenz von extrapyramidalmotorischen Nebenwirkungen ist jedoch nicht höher als unter Plazebo. Die PET erscheint wie keine andere Methode dazu geeignet, in vivo am menschlichen Gehirn ein neues Prinzip für die „Atypie” einer neuen Klasse von Antipsychotika zu erschließen.

Abstract

Almost fifteen years of research with Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have led to a profound understanding of the relationships between antipsychotic doses and plasma levels on the one hand and occupancy of (striatal) D2-like dopamine receptors on the other hand as well as with the associated clinical effects and side effects. Furthermore, with the development of clinically „atypical” antipsychotics PET studies helped to generate hypotheses regarding the essential pharmacological properties of this heterogeneous class of drugs. Possible mechanisms of action include combined D2-/5-HT2 antagonism, preferential mesolimbic binding, and fast dissociation from the D2-receptor. Our recently published PET study on the in vivo characterization of the partial dopamine receptor agonist, aripiprazole, suggests a novel mechanism of action, which leads to clinically „atypical” properties of an antipsychotic. Aripiprazole, of which the antipsychotic efficacy has been proven in various multicenter clinical trials, leads to almost complete saturation of D2-like dopamine receptors at clinically used doses; however, the incidence of extrapyramidal side effects under aripiprazole is not higher than under placebo. PET like no other method is suitable to display in vivo a novel mechanism of „atypicality” of a new class of antipsychotics.

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Priv.-Doz. Dr. med. Gerhard Gründer

Psychiatrische Klinik und Poliklinik · Universität Mainz

Untere Zahlbacher Str. 8

55131 Mainz

Email: gruender@mail.uni-mainz.de

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