title: Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas.
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.
authors.affiliation: Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, and JARA-Translational Brain Medicine, Germany. ivernaleken@ukaachen.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.forename: Hildegard
authors.initials: H
authors.lastname: Janouschek
authors.forename: Mardjan
authors.initials: M
authors.lastname: Raptis
authors.forename: Sandra
authors.initials: S
authors.lastname: Hellmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Veselinovic
authors.forename: Anno
authors.initials: A
authors.lastname: Bröcheler
authors.forename: Christian
authors.initials: C
authors.lastname: Boy
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Schäfer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism; D001549:Benzamides / Q000378:metabolism; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003987:Dibenzothiazepines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000378:metabolism; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D003987:Dibenzothiazepines; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000069348:Quetiapine Fumarate