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Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas
Journal article   Open access   Peer reviewed

Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas

Ingo Vernaleken, Hildegard Janouschek, Mardjan Raptis, Sandra Hellmann, Tanja Veselinovic, Anno Bröcheler, Christian Boy, Paul Cumming, Christoph Hiemke, Frank Rösch, …
The international journal of neuropsychopharmacology, Vol.13(7), pp.951-960
08/2010
DOI: 10.1017/S1461145710000374
PMID: 20392299
url
https://doi.org/10.1017/S1461145710000374View
Published (Version of record) Open Access

Abstract

Quetiapine is next to clozapine an antipsychotic agent that exerts hardly any extrapyramidal side-effects at clinical efficacious doses. Some previous receptor occupancy studies reported preferential extrastriatal D2/3 receptor (D2/3R)-binding properties of second-generation antipsychotics and suggested this as possible reason for improved tolerability. This positron emission tomography (PET) investigation was designed to compare the occupancy of dopamine D2/3Rs by quetiapine in striatal and extrastriatal brain regions. Therefore, a cohort of 16 quetiapine-treated psychotic patients underwent an [18F]fallypride (FP) PET scan. Due to the high affinity of FP and its comparatively long half-life, striatal and extrastriatal binding potentials could be determined in one single scan. Receptor occupancy was calculated as percent reduction in binding potential relative to age-matched medication-free patients suffering from schizophrenia. Quetiapine occupied 44±18% in the temporal cortex and 26±17% in the putamen, a difference significant at the level of p=0.005 (Student's t test). Quetiapine showed a mean occupancy of 36±16% and in the thalamus. In the caudate nucleus there was an occupancy of 29±16% (p=0.0072). Individual occupancy levels did not exceed 59% in any of the striatal volumes of interest. The time-interval between scan and last drug ingestion did not influence the relationship between plasma concentration and central D2/3R occupancy. Taken together, quetiapine shows preferential extrastriatal binding at D2/3Rs; the extent of this difference is comparable to that previously described for clozapine. Both antipsychotics show very low affinity for D2/3Rs.
Schizophrenia preferential extrastriatal binding quetiapine Antipsychotics D2/3 receptor occupancy positron emission tomography

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